SNPMiner Trials by Shray Alag


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Report for Mutation K103N

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 19 clinical trials

Clinical Trials


1 A Multicenter, Randomized, Double-Blind, Comparative Trial Of A Novel CCR5 Antagonist, UK-427,857, In Combination With Zidovudine/Lamivudine Versus Efavirenz In Combination With Zidovudine/Lamivudine For The Treatment Of Antiretroviral-Naive HIV-1 Infected Subjects

Maraviroc (UK-427,857), a selective and reversible CCR5 coreceptor antagonist, has been shown to be active in vitro against a wide range of clinical isolates (including those resistant to existing classes). In HIV-1 infected patients, maraviroc (UK-427,857) given as monotherapy for 10 days reduced HIV-1 viral load by up to 1.6 log, consistent with currently available agents. Safety and toleration have been studied in over 400 subjects for up to 28 days at 300 mg twice daily. No significant effects were seen on the QTc interval. The goal of this study is to compare the safety and efficacy of maraviroc (UK-427,857) versus efavirenz, when each are combined with two other antiretroviral agents, in patients who are previously naive to antiretroviral therapy. This study will involve approximately 200 centers from around the world to achieve a total randomized subject population of 1071 subjects. Patients will be randomly assigned to one of three groups: maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily), Maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily) or efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily). The study will enroll over approximately an 18 month period (5 months Phase 2b run-in, 13 months Phase 3) with 96 weeks of treatment. This may be extended for an additional 3 years depending on the results at 96 weeks. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Blood samples will also be taken at study entry, weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Additionally, blood samples will be drawn twice, at least 30 minutes apart, at weeks 2 and 48 for maraviroc (UK-427,857) pharmacokinetic analysis. As part of this clinical study a blood sample will be taken for non-anonymized pharmacogenetic analysis. Patients will undergo a 12-lead electrocardiogram at study entry, weeks 24, 48 and 96. A computerized tomography (CT) scan will also be performed, at selected centers, at study entry and week 96. Patients will be asked to complete a symptom distress questionnaire at study entry, weeks 12, 24, 48 and 96.

NCT00098293 HIV-1 Drug: Maraviroc + Zidovudine/Lamivudine Drug: Efavirenz + Zidovudine/Lamivudine Drug: Maraviroc (UK-427,857) + Zidovudine/Lamivudine

Efavirenz mutation:lysine to aspargine at r103(K103N);tyrosine to cysteine/isoleucine at r181(Y181C/I);tyrosine to cysteine/leucine/histidine at r188(Y188C/L/H);glycine to alanine/serine at r190(G190A/S);valine to alanine to r106(V106A);leucine to isoleucine at r100(L100I);alanine to glycine at r98(A98G);lysine to glutamic acid at r101(K101E);valine to isoleucine at r108(V108I);proline to histidine at r225(P225H);methionine to leucine at r230(M230L).. Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL at Week 48 and Week 96 by Overall Susceptibility Score (OSS) at Screening. --- K103N ---

Primary Outcomes

Measure: Percentage of Participants With Viral Load of Less Than 400 Copies/Milliliter [Copies/mL] and Less Than 50 Copies/mL of Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) at Week 48 for Full Analysis Set (FAS) Population

Time: Week 48

Description: Percentage of participants with viral load of less than 400 copies/mL and less than 50 copies/mL of HIV-1 RNA were not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.

Measure: Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 48 for Per Protocol (PP) Population

Time: Week 48

Secondary Outcomes

Measure: Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 48 Analyzed Using Logistic Regression

Time: Week 48

Measure: Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 96 Analyzed Using Logistic Regression

Time: Week 96

Description: Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.

Measure: Change From Baseline in Log 10-transformed Plasma Viral Load (HIV-1 RNA) Levels at Week 48 and 96

Time: Baseline, Week 48, Week 96

Description: TAD from baseline was calculated as area under the curve (AUC) of HIV-1 RNA load (log10 copies/mL) divided by time period minus baseline HIV-1 RNA load (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose. Data not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.

Measure: Time-Averaged Difference (TAD) in log10-transformed HIV-1 RNA Levels

Time: Baseline up to Week 48 and Week 96

Description: Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose.

Measure: Change From Baseline in Lymphocyte Cluster of Differentiation 4 (CD4) Count at Week 48 and 96

Time: Baseline, Week 48, Week 96

Description: Baseline value calculated as the average of pre-dose measurements collected at screening and immediately pre-dose. Change from baseline in lymphocyte CD8 count at Week 48 and 96 was not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.

Measure: Change From Baseline in Lymphocyte Cluster of Differentiation 8 (CD8) Count at Week 48 and 96

Time: Baseline, Week 48, Week 96

Description: Time to virologic failure based on observed HIV-1 RNA levels and failure events (death;permanent discontinuation of drug;lost to follow-up [LTFU];new anti-retroviral drug added [except background drug change to drug of same class];or on open label for early non-response or rebound). Failure:at Time 0 if level not <400 copies/mL(2 consecutive visits) before events or last available visit;at time of earliest event if level <400 copies/mL(2 consecutive visits);failure if level >=400 copies/mL(2 consecutive visits) or 1 visit >=400 copies/mL followed by permanent discontinuation of drug or LTFU.

Measure: Time to Virologic Failure

Time: Week 48, Week 96

Description: Number of participants per tropism status (C-X-C chemokine receptor 5 {CCR5} [R5], C-X-C chemokine receptor type 4 {CXCR4} [X4], Dual/mixed [DM], or Non-reportable/Non-phenotypable [NR/NP]) at baseline and time of treatment failure analyzed through week 48 visit. Treatment failure: discontinuation due to insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as below lower limit of quantification (BLQ). The assessment for time of treatment failure was defined as last on treatment assessment.

Measure: Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48

Time: Baseline, time of failure through Week 48

Description: Number of participants per tropism status (R5, X4, DM, or NR/NP) at baseline and time of treatment failure analyzed through week 96 visit. Treatment failure defined as insufficient clinical response. Tropism result was censored for participants with viral load <500 copies/mL at time of treatment failure categorized as BLQ. The assessment for time of treatment failure was defined as last on treatment assessment.

Measure: Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 96

Time: Baseline, time of failure through Week 96

Description: Phenotypic resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) assessed at screening by Monogram Bioscience PhenoSense genotype (MBPSGT) assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Phenotypic resistance to maraviroc was assumed in maraviroc treatment failures with X4-using virus and in R5 maraviroc treatment failures using Monogram Bioscience PhenoSense Entry Assay. Phenotypic resistance to zidovudine, lamivudine, efavirenz and maraviroc at time of failure was summarized.

Measure: Number of Participants With Phenotypic Resistance at Time of Treatment Failure Through Week 48 and 96

Time: Screening, time of failure through Week 48, Week 96

Description: Genotypic resistance to NRTIs was assessed by identification of relevant mutations at screening using MBPSGT assay and repeated for all participants with HIV-1 viral load more than 500 copies/mL at treatment failure through week 48 and week 96. Following mutations associated with NRTIs were summarized at time of failure: Any zidovudine/lamivudine (Zid/Lam), Any thymidine analogue-associated mutation (TAM), methionine (M) to valine/isoleucine (V/I) substitution at residue (r) 184 (M184V/I), lysine (K) to arginine (R) substitution at residue 65 (K65R) and any other NRTI mutations.

Measure: Number of Participants With NRTI Associated Mutations at Time of Treatment Failure Through Week 48 and 96

Time: Screening, time of failure through Week 48, Week 96

Description: Genotypic resistance: mutations at screening by MBPSGT assay, repeated if viral load >500 copies/mL at treatment failure through week 48, 96. Efavirenz mutation:lysine to aspargine at r103(K103N);tyrosine to cysteine/isoleucine at r181(Y181C/I);tyrosine to cysteine/leucine/histidine at r188(Y188C/L/H);glycine to alanine/serine at r190(G190A/S);valine to alanine to r106(V106A);leucine to isoleucine at r100(L100I);alanine to glycine at r98(A98G);lysine to glutamic acid at r101(K101E);valine to isoleucine at r108(V108I);proline to histidine at r225(P225H);methionine to leucine at r230(M230L).

Measure: Number of Participants With Efavirenz Associated Mutations at Time of Treatment Failure Through Week 48 and 96

Time: Screening, time of failure through Week 48, Week 96

Description: Association between baseline resistance and virological response was assessed as percentage of participants with HIV-1RNA levels less than 50 copies/mL by OSS at screening. OSS categorized as 0, 1, 2, >3 (maximum value of 6) and calculated as the sum of the net assessment of in-vitro phenotypic and genotypic susceptibility using a binary scoring system (0= resistant, 1= sensitive or susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.

Measure: Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL at Week 48 and Week 96 by Overall Susceptibility Score (OSS) at Screening

Time: Baseline, Week 48, Week 96

Other Outcomes

Measure: Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 96

Time: Week 96

2 A Randomized, Open-Label Study Assessing Safety, Tolerability and Efficacy of an Induction-Maintenance Treatment Strategy Including Lopinavir/Ritonavir Plus Tenofovir Disoproxil Fumarate and Emtricitabine Versus Efavirenz Plus Tenofovir Disoproxil Fumarate and Emtricitabine in Antiviral-naïve HIV-1/HCV Co-Infected Subjects

The purpose of this study is to determine whether a simplified lopinavir/ritonavir-based therapy will continue to keep the viral load at very low levels after initial treatment with a combination of Kaletra (lopinavir/ritonavir) plus tenofovir and emtricitabine.

NCT00121017 HIV Infection Hepatitis C Drug: Kaletra (lopinavir/ritonavir) Drug: Sustiva (efavirenz) Drug: Truvada (emtricitabine/tenofovir disoproxil fumarate)
MeSH: Hepatitis C

- The screening HIV-1 genotype resistance report suggests resistance or possible resistance to the study RTI(s) or lopinavir/ritonavir; Evidence of possible resistance to efavirenz; Presence of one of the following mutations: RT L1001, K103N, V106A or M, V108I, Y181C or I, Y188L, G190A or S, P225H, M230L; Evidence of possible resistance to emtricitabine or lamivudine; Presence of one of the following mutations: RTm184V or I; Evidence of possible resistance to tenofovir; Presence of RT K65R or insertion at codon 69, or Presence of 2 or more of the following mutations: RTm41L, D67N, K70R, L210W; any change at T215, K219Q or evidence of possible resistance to lopinavir/ritonavir; Presence of one or more of the following mutations: protease I47V or A, G48V, I50V, V82A or F or T or S, I84V, 190M or Presence of 3 or more of the following mutations: protease L10F or I or R or V, K20M or R, L24I, V32I, L33F, M36I, M46I or L, F53L; any change at I54, A71V or T, G73S. --- K103N ---

Primary Outcomes

Measure: The proportion of subjects with a plasma HIV-1 RNA level below 50 copies/mL at Week 96.

Secondary Outcomes

Measure: Vital signs

Measure: Physical examinations

Measure: Clinical laboratory tests

3 An Evaluation of the Development of Nevirapine Induced Mutations in HIV Patients Initiating or Discontinuing Combination Antiretroviral Therapy

Hypothesis Nevirapine resistance developed in women and infants in the HIVNET 006 and 012 cohorts as a consequence of use of an agent with a long t½ as monotherapy in individuals with high viral loads. Objective 1 To demonstrate that Nevirapine resistance does not develop in HIV infected patients when used as part of triple antiretroviral combination therapy between the initiation of treatment and suppression of HIV RNA to <1000 copies/ml. Objective 2 To demonstrate that resistance to nevirapine does not develop when patients with suppressed HIV RNA discontinue combination antiretroviral therapy which contains nevirapine.

NCT00193947 Drug Resistance

The K103N was the most common mutation. --- K103N ---

Similarly, the K103N resistance mutation was detected 6 weeks after Nevirapine administration in 3/15 (20%) women in the HIVNET006 phase I/II trial. --- K103N ---

Primary Outcomes

Measure: To demonstrate that Nevirapine resistance does not develop in HIV infected patients when used as part of triple antiretroviral combination therapy between the initiation of treatment and suppression of HIV RNA to <1000 copies/ml.

Time: during viral suppression

Secondary Outcomes

Measure: to determine whether ARV resistance emerges when pregnant women discontinue ARV

Time: 6 months after drug discontinutation or until viral rebound

4 Pharmacogenetics of Efavirenz Metabolism: Association of CYP2B6 Genotype and Prolonged Drug Exposure

This study will evaluate the effects of genetics on metabolism of the anti-HIV medicine efavirenz (Sustiva) and will see if Efavirenz interacts with bupropion (Zyban or Wellbutrin), a drug commonly used to treat depression and to help people quit smoking. Efavirenz is metabolized by an enzyme called CYP2B6, which is thought to be more active in some people than in others, depending on their genetic makeup. The rate of metabolism of the drug can affect how the body responds it and perhaps the ability of the HIV virus to develop resistance to it. Healthy volunteers between 18 and 55 years of age who are non-smokers and HIV-infected men and women 18 years of age and older who are taking efavirenz along with two or three nucleoside reverse transcriptase inhibitors may be eligible for this study. Candidates are screened with a medical history and physical examination and blood tests, including tests to determine which genes they have for four different proteins or enzymes (CYP2B6, CYP3A4, CYP3A5, and MDR1) that metabolize drugs. Participants are assigned to one of three groups for the following procedures: -HIV-infected individuals: Blood samples are drawn to measure efavirenz levels, as follows: On the last day of taking efavirenz, the subject skips his or her usual evening efavirenz dose the night before sampling. The next morning at clinic, a catheter (flexible plastic tube) is inserted into a vein in the subject's arm for collecting blood samples. After the first sample is drawn, the subject takes a dose of efavirenz. Eight more blood samples are collected at 1, 2, 4, 6, 8, 12, 24 and 48 hours after taking the efavirenz tablet. (The catheter is removed after the 12-hour sample and the subject is discharged home, and then returns to the clinic for the 24- and 48-hour samples, which are collected through a needle inserted into an arm vein.) The subject returns to the clinic four more times for a single blood draw at 7, 14, 21 and 28 days after stopping efavirenz. HIV-infected patients whose HIV viral load reaches 1,000 copies/L or more within 12 months after completing the study are asked to return to the clinic for a blood draw to check the genotype of the virus for drug resistance. - Healthy Volunteers - Group 1: Blood samples are drawn to measure efavirenz levels, as follows: Participants take one efavirenz tablet once a day for 13 to 15 days. On the last day of taking efavirenz, the subject takes his/her last dose of efavirenz in clinic, where blood is then collected as described above for HIV-infected individuals. - Healthy Volunteers - Group 2: A catheter is inserted into a vein in the subject's arm and a blood sample is drawn through the catheter. The subject then takes a single bupropion tablet and additional blood samples are drawn at 1,2, 2.5, 3, 3.5, 4, 6, 8, 12, 24 and 48 hours after the dose to measure the amount of drug in the blood. Subjects begin taking efavirenz 0 to 6 days after the last bupropion blood level is measured. As above, subjects will take one efavirenz tablet once a day for 13 to 15 days. On the last day of taking efavirenz, a catheter is inserted into the subject's arm. Two blood samples are drawn through the catheter, the subject takes the daily dose of efavirenz along with a bupropion tablet. Eleven additional blood samples are drawn at 1, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, and 48 hours after taking the pills to measure blood levels of bupropion. Eight additional samples are collected at 1, 2, 4, 6, 8, 12, 24, and 48 hours to measure efavirenz blood levels. (The catheter is removed after the 12-hour sample and the subject is discharged home; the 24- and 48-hour samples are collected through a needle inserted into an arm vein.)

NCT00245986 Metabolism Procedure: Blood draw

The single K103N mutation confers high-level resistance to EFV, as well as to all other NNRTI's. --- K103N ---


5 Directly Administered vs. Self-administered Antiretroviral Therapy in Methadone Clinics

The purpose of this study is to determine whether providing directly administered antiretroviral therapy to HIV-infected who receive methadone therapy leads to better treatment outcomes than if they take HIV medications on their own.

NCT00279110 HIV Infections Heroin Dependence Behavioral: Directly administered antiretroviral therapy (DAART)
MeSH: Heroin Dependence

Current plasma HIV RNA > 500 copies/ml 7. Initiating ART for first time, reinitiating therapy after stopping, or changing therapy due to virologic failure 8. ART with at least 3 agents, including a protease inhibitor, a non-nucleoside reverse transcriptase inhibitor, or abacavir 9. Methadone or buprenorphine maintenance therapy > 3 weeks, with no planned detoxification Exclusion Criteria: 1. Need to use ART dosed more frequently than twice daily, 2. Need to use a liquid preparation of antiretroviral medication, 3. Documented triple-class antiretroviral resistance (defined below), 4. Participation in another study or program that includes directly observed therapy. 5. Use of ART regimens that are expressly discouraged in DHHS HIV clinical care guidelines Triple-class antiretroviral resistance will be defined according to IAS-USA interpretive guidelines: NRTI class - 3 thymidine or non-thymidine-associated mutations (excluding the M184V mutation) or a multi-nucleoside resistance mutation in reverse transcriptase; PI class - 3 protease mutations, including 1 primary mutation; NNRTI class - 1 primary (K103N or Y188L) or 2 secondary NNRTI-associated mutations in reverse transcriptase. --- M184V --- --- K103N ---

Primary Outcomes

Measure: HIV RNA < 50 c/mL

Time: 12 months

Secondary Outcomes

Measure: Log10 change in HIV RNA from baseline

Time: 12 months

Measure: HIV RNA < 50 c/mL 6 mos. after intervention

Time: 18 months

Measure: Log10 change in HIV RNA from baseline 6 months post intervention

Time: 18 months

Measure: Change in CD4 cell count from baseline

Time: 18 months

Measure: ART utilization

Time: 12 months

Measure: Development of antiretroviral resistance

Time: 12 months

Measure: Retention to substance abuse treatment

Time: 12 months

Measure: Urine drug screen positivity in follow-up

Time: 12 months

Measure: Electronically monitored adherence

Time: 2 months

6 Cell Cycle Independent Antiretroviral Therapy: Combination of Nevirapine, FTC, and Tenofovir

Open label, two year study of the clinical efficacy of the combination of FTC, Tenofovir, and Nevirapine. Sixty HIV infected patients without previous exposure to antiretroviral therapy will be enrolled. Study will include a pharmacokinetic substudy to evaluate the interaction of FTC and Nevirapine. Truvada may be used.

NCT00344461 HIV Drug: Nevirapine, FTC, and Tenofovir

Evidence of mutation associated with primary drug resistance to Nevirapine (K103N, Y181C, Y188L, G190S), Tenofovir (M41L, T69 insertion, Q151M, L210W,and K65R), and/or FTC (184V) previously documented, or at time of screening. --- K103N ---

Primary Outcomes

Description: The primary outcome is sustained Virologic response, defined as HIV-1 RNA <500 copies/mL until trial completion at 96 weeks.

Measure: Number of Participants With Sustained Virologic Response

Time: 96 Weeks

Secondary Outcomes

Description: The number of participants with grades 2,3 and 4 adverse events and laboratory toxicities.

Measure: Patients With Grade 2, 3 and 4 Adverse Events and Laboratory Toxicities

Time: Protocol length is 96 weeks

Description: The number of participants with plasma HIV RNA < 50 copies/mL

Measure: Patients With Plasma HIV RNA < 50 Copies/mL

Time: 96 weeks.

Description: The number of participants with plasma HIV RNA < 400 copies/mL

Measure: Patients With Plasma HIV RNA < 400 Copies/mL

Time: 96 weeks

Description: Percent Change From Baseline in Plasma HIV RNA at 96 weeks

Measure: Change in Plasma HIV RNA From Baseline to Week 96

Time: Baseline to week 96

Description: To determine the mean change from Baseline in CD4 cell count to week 96.

Measure: Changes in CD4 Cell Count From Baseline and Week 96

Time: Baseline to week 96

7 Open-Label, Single-Centre, Randomised Pilot Study to Evaluate Immunovirological and Clinical Evolution of a Combination With Nucleoside Analogues/Nucleotides (Trizivir +Tenofovir) in Multiresistant Patients With Virological Failure

To evaluate whether the combined therapy of two nucleosides plus one nucleotide (Trizivir + TDF) manages to keep CD4 lymphocytes stable in patients with HIV infection on antiretroviral treatment that present virological failure and multiple resistance to antiretrovirals.

NCT00356616 HIV Infections Drug: Trizivir (AZT+3HT+Abacavir) twice daily Drug: Viread (300 mg Tenofovir disoproxil fumarate) once daily
MeSH: HIV Infections

- Existence of 1 or more mutations that confer resistance to NNRTI, or probable presence in the cellular archives of: K103N, Y181C/I/Y, G190S/A/G. --- K103N ---

Primary Outcomes

Measure: Variations in the immune status of patients in each group throughout follow-up.

Time: 48 weeks

Secondary Outcomes

Measure: Percentage of patients that increase viral load by > 0.5 log

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that increase viral load by > 100,000 copies/mL

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that present some clinical event, B or C classification according to the CDC.

Time: during the 48 weeks of follow-up

Measure: Percentage of patients that present clinical or analytical adverse effects degree > 2 according to the WHO classification.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that drop out of treatment.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that drop out of the study due to intolerance or adverse effects.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of change in lipid determinations.

Time: weeks 12, 24, 36 and 48 with regard to baseline

Measure: Percentage of patients that report changes, improvement or worsening in redistribution of body fat.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that present adherence to the antiretroviral treatment > 95%.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that present improvement in the quality of life (MOS-HIV) and satisfaction questionnaires.

Time: weeks 12, 24, 36 and 48

Measure: Percentage of patients that present an increase in the number of active drugs.

Time: at the end of the study

8 Phase 2 Dose-escalating, P-C, D-B, Parallel Group Study in HIV Treatment-experienced Patients to Evaluate the Safety, Tolerability and Efficacy of PA103001-04 Administered as Functional Monotherapy for 14 Days *(PART B)

The purpose of this study is to evaluate antiretroviral activity of up to five different oral doses administered for two weeks of bevirimat versus placebo in HIV treatment experienced patients, who have documented genotypic resistance to at least one major mutation from the IAS-USA list (2007)of resistance mutations for NRTIs, NNRTIs, or PIs. Patients will also be monitored for side effects, and the pharmacokinetics of bevirimat will be determined.

NCT00511368 HIV Infections Drug: matching placebo Drug: Bevirimat
MeSH: HIV Infections

- Have documented evidence of genotypic resistance in their medical records (at screening) or have resistance at screening by genotype to any major mutation from the IAS-USA list of resistance drug mutations, defined as: NRTI resistance: M41L, K65R, D67N, K70R, K70E, L74V, Y115F, M184V, M184V/I, L210W, T215Y/F, K219Q/E; NNRTI resistance: L100I, K103N, V106M, V106A/M, V108I, Y181C, Y181C/I, Y188L, Y188C/L/H, G190S/A, G190A, P225H; Major PI resistance: D30N, V32I, L33F, M46I/L, I47V/A, G48V, I50L, I50V, I54M/L, L76V, V82A/F/T, V82A/F/T/S, V82L/T, I84V, N88S, L90M - Be receiving an antiretroviral therapy regimen containing at least 3 drugs (regimens containing ritonavir must not exceed a total daily dose of 400 mg) which has been unchanged for at least 8 weeks prior to initial screening. --- M41L --- --- K65R --- --- D67N --- --- K70R --- --- K70E --- --- L74V --- --- Y115F --- --- M184V --- --- M184V --- --- L210W --- --- T215Y --- --- K219Q --- --- L100I --- --- K103N ---

Primary Outcomes

Measure: HIV-1 RNA change from baseline over the first 14 days of study

Time: 14 days

Secondary Outcomes

Measure: safety and tolerability; pharmacokinetics

Time: 14 days

9 A Study in Underrepresented Patient Population or Regimen Tolerability: SUPPoRT

The hope of this study is to gather data and information about the tolerability and effectiveness of Lexiva versus Sustiva in patients who have have been generally underrepresented in clinical trials.

NCT00727597 Human Immunodeficiency Virus Infections Drug: Efavirenz 600mg Drug: Boosted Lexiva
MeSH: Acquired Immunodeficiency Syndrome HIV Infections Virus Diseases

v. Sterilization (female subject or male partner of female subject) Exclusion Criteria: Screening HIV-1 genotype indicating the presence of any of the following mutations in the reverse transcriptase (RT) region: K65R, L74V, K103N, Y115F, Y181C/I, Y188C/L/H or G190S/A, or a combination of two or more thymidine analog mutations (M41L, D67N, K70R, K219Q or E) that include changes at either L210 or T215, associated with resistance to abacavir, lamivudine, or efavirenz; OR within the protease region, detection of any of the following mutations associated with resistance to fosamprenavir or ritonavir: I50V, I54L/M, I84V, or the combination of the two mutations V32I+I147V Positive for Hepatitis B surface antigen (HBsAg+) Requirement for active treatment for hepatitis C virus infection, as indicated by both a positive Hepatitis C Virus serology AND either: 1. Decompensated liver disease, or 2. Aspartate aminotransferase (AST) >3X the upper limit of normal (ULN), or 3. Alanine aminotransferase (ALT) >3X the ULN Currently pregnant, intending to become pregnant during the study period, or breast-feeding Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), any vaccinations, systemic cytotoxic chemotherapy, or investigational therapy within 28 days prior to study entry. --- K65R --- --- L74V --- --- K103N ---

Primary Outcomes

Description: Subjects were randomized and initiated treatment on one of the antiretroviral arms(FPV/r or EFV) at study Entry visit. Subjects would be switched for the follwing reasons: To resolve a Grade 3 or 4 Adverse Event The subject experienced a virologic failure (as defined in section 3.6.2) The investigator believes the subject is at a significant risk for failing to comply with the protocol AND the investigator believes a regimen substitution is likely to resolve the compliance issue The investigator believes there is any other significant safety concern for the subject associated with remaining on the current regimen (e.g., hypersensitivity reaction, increased risk of suicide)

Measure: Number of Subjects Needing to Switch Comparator Drugs (FPV/r or EFV)

Time: 96 weeks

Measure: Number of Subjects Developing Any Treatment-related Grade 3-4 Adverse Events

Time: 96 weeks

10 Antiretroviral Activity and Tolerability of Once Daily Etravirine in Treatment-Naïve Adults With HIV-1 Infection

The main study is a single arm, open-label, prospective study to assess antiretroviral activity and tolerability of etravirine (TMC-125) 400 mg once daily, given with fixed-dose tenofovir/emtricitabine, in treatment-naïve HIV-1-infected men and women. There are also a genital secretions pharmacokinetic (PK) sub-study and a metabolic sub-study. The purpose of the genital secretions PK sub-study is to gain information about drug levels and HIV-1 RNA in genital secretions when subjects are taking etravirine. The purpose of the metabolic sub-study is to learn about the effects of etravirine on body composition, as well as lipid and glucose levels.

NCT00959894 HIV Infections Drug: Etravirine (Intelence) Drug: Truvada
MeSH: Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome

Any of the following nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations: V90I, A98G, L100I, K101E/H/P/Q, K103H/S/T, V106A/I/M, V108I, E138A/G/K/Q, V179D/E/F/G/I/T, Y181C/I/V, Y188C/H/L, V189I, G190A/C/E/Q/S, H221Y, P225H, F227C/L, M230I/L, P236L, K238N/T, K103N. --- V90I --- --- A98G --- --- L100I --- --- K101E --- --- K103H --- --- V106A --- --- V108I --- --- E138A --- --- V179D --- --- Y181C --- --- Y188C --- --- V189I --- --- G190A --- --- H221Y --- --- P225H --- --- F227C --- --- M230I --- --- P236L --- --- K238N --- --- K103N ---

Primary Outcomes

Description: The primary study endpoint was the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 24 of study participation. The per-protocol primary analysis was conducted intention-to-treat, with missing evaluations counted as failures. Achievement of HIV-1 viral load below 50 copies/ml was defined as having HIV-1 RNA <50 copies/ml during the Week 24 analysis window (>18 and <30 weeks post-entry).

Measure: The Antiretroviral Activity of Etravirine 400 mg Given Once Daily, With Fixed-dose Truvada Once Daily, Among Treatment-naïve HIV-1 Infected Adults as Measured by the Percentage of Participants With HIV RNA < 50 Copies/mL at Week 24

Time: 24 weeks

Secondary Outcomes

Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 48 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <50 Copies/mL at Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 48 weeks

Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <50 copies/ml at Week 96 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <50 Copies/mL at Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 96 weeks

Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <200 copies/ml at Week 24 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <200 Copies/mL at Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 24 weeks

Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA <200 copies/ml at Week 48 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <200 Copies/mL at Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 48 weeks

Description: This secondary outcome assessed the proportion of participants who achieved HIV-1 RNA 200 copies/ml at Week 96 of study treatment. The per-protocol analysis was conducted intention-to-treat, with missing evaluations counted as failures.

Measure: The Proportion of Participants With HIV RNA <200 Copies/mL at Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 96 weeks

Description: The per-protocol analysis of change in CD4+ cell count from baseline to Week 24 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% confidence interval (CI).

Measure: Change in CD4+ Cell Count From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

Description: The per-protocol intention-to-treat analysis of change in CD4+ cell count from baseline to Week 48 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% CI.

Measure: Change in CD4+ Cell Count From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 48 weeks

Description: The per-protocol intention-to-treat analysis of change in CD4+ cell count from baseline to Week 96 was calculated using the measurement closest to schedule and within the analysis window, and quantified with an estimated median and distribution-free 95% CI.

Measure: Change in CD4+ Cell Count From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

Description: Per-protocol, genotype testing was conducted at confirmation of virologic failure if the confirmatory HIV-1 RNA was above the laboratory-specified threshold of 500 copies/mL. HIV-1 genotype was determined using the TRUGENE® HIV-1 assay (Siemens Healthcare Diagnostics, Tarrytown, NY)

Measure: Resistance Mutations in the Subset of Patients With Confirmed Virologic Failure Who Have HIV RNA >500 Copies/mL and Genotype Resistance Results

Time: 96 weeks

Description: The safety/tolerability endpoint was defined as the first grade 3 or higher sign, symptom or laboratory abnormality that was at least one grade higher than baseline among participants ever exposed to etravirine (regardless of treatment status), or permanent discontinuation of etravirine due to any toxicity (regardless of grade). Modification of tenofovir/emtricitabine was not a safety/tolerability event. The Kaplan-Meier method was used to estimate the proportion of participants ever exposed to etravirine who remained event-free through Week 96, with a 95% CI using Greenwood's variance estimate and a log-log transformation. Time was handled as continuous (weeks from treatment start to event or censoring).

Measure: Tolerability of Etravirine in HIV-1 Infected Adults Initiating Antiretroviral Therapy

Time: 96 weeks

Description: The Kaplan-Meier method was used to estimate the proportion of participants ever exposed to etravirine who remained event-free through Week 96, with a 95% CI using Greenwood's variance estimate and a log-log transformation. Time was handled as continuous (weeks from treatment start to event or censoring).

Measure: Probability of Remaining Free of a Safety/Tolerability Event at 96 Weeks

Time: 96 weeks

Description: Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

Description: Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

Description: Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 48 weeks

Description: Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 48 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 48 weeks

Description: Metabolic data analyses were conducted as-treated. Changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and fasting blood glucose from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5.

Measure: Change in the Lipid Profile and Glucose Metabolism, in a Subgroup of up to 40 Participants, From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

Description: Metabolic data analyses were conducted as-treated. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR), and was calculated as [fasting insulin (µU/mL) × fasting glucose (mmol/L)]/22.5. Changes from baseline to follow-up were calculated using the value closest to schedule and within the analysis window, and were quantified with the median and inter-quartile range.

Measure: Change in Glucose Metabolism (Insulin Resistance), in a Subgroup of up to 40 Participants, From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

Description: Changes from baseline to follow-up in limb fat, trunk fat, total body fat, and lean mass were calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Limb and Trunk Fat Distribution as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

Description: Changes from baseline to follow-up in limb fat, trunk fat, total body fat, and lean mass were calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Limb and Trunk Fat Distribution as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

Description: Change from baseline to follow-up in fat mass ratio was calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Fat mass ratio was calculated as the ratio of trunk fat percentage and lower limb fat percentage (% trunk fat mass / % lower limb fat mass). Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Fat Mass Ratio as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 24 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 24 weeks

Description: This secondary outcome measure assessed the ratio of semen:plasma concentration of etravirine in paired semen and plasma samples collected from 14 male participants at Week 4 of treatment with etravirine and fixed dose tenofovir/emtricitabine.

Measure: Pharmacokinetics of Etravirine in Genital Secretions of up to 10 Men and up to 10 Women at Week 4 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: 4 weeks

Description: Change from baseline to follow-up in fat mass ratio was calculated. Whole body Dual X-ray Absorptiometry (DEXA) scans (Hologic Discovery W, Hologic Inc., Bedford, MA) were conducted at baseline, Week 24, and Week 96 to assess body fat distribution. Fat mass ratio was calculated as the ratio of trunk fat percentage and lower limb fat percentage (% trunk fat mass / % lower limb fat mass). Calculations of change from baseline to follow-up used the value closest to schedule and within the analysis window, and were quantified with the estimated median and distribution-free 95% CI.

Measure: Change in Fat Mass Ratio as Measured by DEXA Scan, in the Same Subgroup of up to 40 Participants (as in Aim 8), From Baseline to Week 96 of Treatment With Etravirine and Fixed-dose Tenofovir/Emtricitabine

Time: Baseline to 96 weeks

Description: Population pharmacokinetics were calculated using sparse sampling. Plasma concentrations of etravirine measured in samples from participants who provided blood samples at multiple study visits, with variation in sampling times relative to dosing of etravirine used to cover the spectrum of the dosing schedule. Model simulations and fitting were performed with NONMEM ® 7.3. (ICON, plc) and model exploration was performed with Berkeley Madonna (Berkeley, CA, USA)

Measure: Population Pharmacokinetics of Etravirine 400 mg Once Daily, in Combination With Fixed-dose Emtricitabine-tenofovir Among Treatment-naïve HIV-1 Infected Adults

Time: At or after 4 weeks

Description: Population pharmacokinetics were calculated using sparse sampling. Plasma concentrations of etravirine measured in samples from participants who provided blood samples at multiple study visits, with variation in sampling times relative to dosing of etravirine used to cover the spectrum of the dosing schedule. Model simulations and fitting were performed with NONMEM ® 7.3. (ICON, plc) and model exploration was performed with Berkeley Madonna (Berkeley, CA, USA)

Measure: Population Pharmacokinetics of Etravirine 400 mg Once Daily, in Combination With Fixed-dose Emtricitabine-tenofovir Among Treatment-naïve HIV-1 Infected Adults: Etravirine AUC-24 Hours at Steady State

Time: At or after 4 weeks

11 Open Label, Randomized Trial of TDF/FTC+Raltegravir Vs. TDF/FTC+Efavirenz in HIV-1-Infected Women: Differential Effects on Viral Suppression/Reservoir, & Immune Parameters in Different Compartments, Including Gut & Genital Tract

Raltegravir not only has a unique mechanism of action, but may also have other unique effects on suppression of viral replication, viral reservoir, and immune reconstitution in blood and other important compartments. This may in part be due to the pharmacokinetics of Raltegravir in blood and gut tissue. Efavirenz will be the comparator antiretroviral drug in this study, with both drugs being used as part of a three-drug regimen with tenofovir and emtricitabine. The primary objectives are to determine differences in the effects of 2 anti-retroviral regimens, Raltegravir + Truvada versus Atripla, with respect to: 1. Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization). 2. Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract. 3. Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine profiles. The secondary objective is to determine the pharmacokinetics of Raltegravir in blood and gut tissue; relative tissue/compartment penetration compared to Efavirenz.

NCT00984152 HIV-1 Infections Drug: TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily Drug: TDF/FTC + Efavirenz (Atripla) Once-Daily

Exclusion Criteria: 1. Menopausal (may affect quantity of genital tract secretions) or any serious illness that requires treatment and/or hospitalization until the patient completes therapy 2. Any active infection, including co-infection with hepatitis B or C 3. Any neoplasm 4. Immunosuppressive therapy 5. Requirement for any medications that are prohibited by any of the study treatments 6. Significant liver or renal dysfunction 7. Baseline resistance to any of the study drugs by genotypic testing - NRTI: M41L, K65 R, D76N, T69D, K70R, L74V/I, y115F, Q151M, M184V, L210W, T215any, K219Q/E - NNRTI:L100I, K103N, V106A/M, V108I, Y181C/I, Y188C/L/H, G190anyA/S 8. Alcohol or substance abuse problems or psychiatric conditions that impair the ability of the subject to comply with the study protocol Inclusion Criteria: 1. Eligible subjects will be antiretroviral naïve (< 7 days of HAART at any time prior to entry) with plasma HIV-1 RNA > 50,000 copies/mL (obtained within 90 days prior to study entry by any laboratory that has a CLIA certification or its equivalent) and moderate immune suppression within 90 days prior to study entry. --- M41L --- --- D76N --- --- T69D --- --- K70R --- --- L74V --- --- Q151M --- --- M184V --- --- L210W --- --- K219Q --- --- K103N ---

Exclusion Criteria: 1. Menopausal (may affect quantity of genital tract secretions) or any serious illness that requires treatment and/or hospitalization until the patient completes therapy 2. Any active infection, including co-infection with hepatitis B or C 3. Any neoplasm 4. Immunosuppressive therapy 5. Requirement for any medications that are prohibited by any of the study treatments 6. Significant liver or renal dysfunction 7. Baseline resistance to any of the study drugs by genotypic testing - NRTI: M41L, K65 R, D76N, T69D, K70R, L74V/I, y115F, Q151M, M184V, L210W, T215any, K219Q/E - NNRTI:L100I, K103N, V106A/M, V108I, Y181C/I, Y188C/L/H, G190anyA/S 8. Alcohol or substance abuse problems or psychiatric conditions that impair the ability of the subject to comply with the study protocol HIV-1 Infections This is a phase III, prospective, randomized (1:1), multicenter, open label study comparing the effects of two HAART regimens: - Arm A: Raltegravir 400 mg PO BID + TDF/FTC (Truvada, 300/200 mg) One PO Daily - Arm B: Efavirenz + TDF/FTC (Atripla) Once PO Daily The following local sites: Mt. --- M41L --- --- D76N --- --- T69D --- --- K70R --- --- L74V --- --- Q151M --- --- M184V --- --- L210W --- --- K219Q --- --- K103N ---

Primary Outcomes

Measure: Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization)

Time: 48 weeks

Measure: Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract

Time: 48 weeks

Measure: Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine profiles

Time: 48 weeks

Secondary Outcomes

Measure: Determine the pharmacokinetics of Raltegravir in blood and gut tissue; relative tissue/compartment penetration compared to Efavirenz

Time: 48 weeks

12 Dolutegravir + Rilpivirine Switch Study (DORISS): Pilot and Noninferiority Trial Comparing Dolutegravir + Rilpivirine vs. Continued HAART (Highly Active Antiretroviral Therapy) in Patients With Plasma HIV RNA ≤ 50 Copies/mL for at Least 2 Years

The primary objective of the study is to evaluate the capacity of Dolutegravir + Rilpivirine vs. continued triple combination HAART to maintain plasma HIV RNA ≤ 50 copies/ml throughout 24 weeks in patients with plasma HIV RNA ≤ 50 copies/mL for at least 2 years under conventional HAART (2 NNRTI + 3rd agent). The main secondary objectives are the following: - % of virologic success (plasma viral load ≤ 50 copies/mL) at W24 and W48 - % of patients who maintain a plasma viral load ≤ 50 copies / ml from D0 to W48 - % of virological failure defined by two consecutive plasma viral load > 50 copies/mL - Profile of genotypic resistance in case of virological failure. The trial will be conducted according to the design below, in 3 steps: - Step 1: enrollment of 80 patients (40 in each arm) - Step 2: enrollment on hold until W16 data from the 40 patients enrolled in the intervention arm have been analyzed. - Step 3: resumption and completion of enrollment if conditions for resuming enrollment at the end of step 2 are fulfilled, i.e. if the percentage of patients randomized to the intervention arm who have a plasma viral load ≤ 50 copies/mL from D0 to W16 is significantly > 70%, which translates in a maximum of 6 virologic failures.

NCT02069834 HIV Infection HAART-treated Virologically Controlled Drug: Arm 1 (intervention) Drug: Arm 2 (control)
MeSH: HIV Infections

- Plasma HIV-RNA ≤ 50 copies/mL for > 2 years - CD4 cell count > 350/mm3 for > 6 months - No prior virologic failure under an NNRTI-containing or an INSTI-containing ART regimen - No NNRTI mutation on pre-ART genotype (if no pre-ART genotype available: no NNRTI mutation on DNA genotype at screening) among the following: K101E/P, E138A/G/K/Q/R/S, V179L, Y181C/I/V, Y188L, H221Y, M230I/L/V, L100I + K103N/S, L100I +K103R +V179D. --- K101E --- --- E138A --- --- V179L --- --- Y181C --- --- Y188L --- --- H221Y --- --- M230I --- --- L100I --- --- K103N ---

Primary Outcomes

Measure: Pilot phase: Percentage of patients with plasma viral load ≤ 50 copies HIV-RNA/ml from D0 (Day 0) to W16 (Week 16)

Time: Week 16

Measure: Non-inferiority phase: Percentage of patients with plasma HIV RNA maintained ≤ 50 copies/mL throughout 24 weeks

Time: Week 24

Secondary Outcomes

Measure: Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL at Week 24 and Week 48

Time: Week 48

Measure: Percentage of patients with plasma viral load ≤50 HIV RNA copies/mL from Day 0 to Week 48

Time: Week 48

Measure: Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL

Time: Week 48

Measure: Measure of the profile of genotypic resistance in plasma in case of virologic failure

Time: Week 48

Measure: Percentage of patients who discontinued or changed the strategy of the study

Time: Week 48

Description: Evolution of the HIV-DNA between Day 0 and week 48

Measure: Measure of the HIV-DNA between day 0 and week 48

Time: W48

Description: Evolution of CD4 lymphocytes (average) at Week 24 compared to Day 0

Measure: Measure of CD4 lymphocytes at week 24 compared to day 0

Time: Week 24

Description: Evolution of CD4 lymphocytes (average) at Week 48 compared to Day0

Measure: Measure of CD4 lymphocytes at Week 48 compared to Day 0

Time: Week 48

Description: Adverse events : incidence, grade and relation to study medication of all adverse events, of grade 2 to 4 events

Measure: Number of patients with adverse events of grade 2 to 4

Time: Week 48

Description: Mean changes in serum plasma lipid parameters at Week 24 compared to Day 0

Measure: Measure of changes in serum plasma lipid parameters at week 24 compared to Day 0

Time: Week 24

Description: Mean changes in serum plasma lipid parameters at Week 48 compared to Day 0

Measure: Measure of changes in serum lipid parameters at week 48 to Day 0

Time: Week 48

Description: Changes in fat mass distribution at Week 24 compared to Day 0

Measure: Measure of changes in fat mass distribution at week 24 compared to Day 0

Time: Week 24

Description: Changes in fat mass distribution at Week 48 compared to Day 0

Measure: Measure of changes in fat mass distribution at Week 48 compared to Day 0

Time: Week 48

Description: Evolution of adherence to treatment at Week 24 compared to Day 0 assessed by a validated questionnaire

Measure: Measure of adherence to treatment at Week 24 compared to Day 0

Time: Week 24

Description: Evolution of adherence to treatment at Week 48 compared to Day 0 assessed by a validated questionnaire

Measure: Measure of adherence to treatment at Week 48 compared to Day 0

Time: Week 48

Description: Assessment of patient satisfaction for their treatment at D0 by questionnaire

Measure: Measure of patient satisfaction for their treatment at Day 0

Time: Day 0

Description: Assessment of patient satisfaction for their treatment at Week 24 by questionnaire

Measure: Measure of patient satisfaction for their treatment at Week 24

Time: Week 24

Description: Assessment of patient satisfaction for their treatment at Week 48 by questionnaire

Measure: Measure of patient satisfaction for their treatment at Week 48

Time: Week 48

Description: Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .

Measure: Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 24 compared to Day 0 .

Time: Week 24

Description: Changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .

Measure: Measure of changes in plasma biomarkers of inflammation (hs-CRP and IL-6) and immune activation (sCD14 , MCP -1, IP10 ) at Week 48 compared to Day 0 .

Time: Week 48

Description: Analysis PK (PharmacoKinetic) / PD (Pharmaodynamic) of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4

Measure: Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 4

Time: Week 4

Description: Analysis PK / PD of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24

Measure: Measure of plasma concentrations of Dolutegravir and Rilpivirine measured at Week 24

Time: Week 24

Measure: Measure of the profile of genotypic resistance in plasma in case of virologic failure

Time: Week 24

Measure: Percentage of virologic failure, defined as 2 consecutive plasma HIV RNA > 50 copies/mL

Time: Week 24

13 A Phase IV 48 Week, Open Label, Pilot Study of Darunavir Boosted by Cobicistat in Combination With Rilpivirine to Treat HIV+ Naïve Subjects (PREZENT)

Current HIV treatment guidelines recommend the use of triple-drug therapy (two nucleoside reverse transcriptase inhibitors and either a protease inhibitor, non-nucleoside reverse transcriptase inhibitor, or an integrase inhibitor) for the treatment of antiretroviral (ARV)-naïve patients. With the introduction of highly active antiretroviral therapy (HAART), patients with HIV are living much longer. With the increasing lifespan of persons with HIV, long-term complications from therapy as well as the occurrence of co-morbidities with aging have prompted HCPs to re-think the current treatment paradigm and consider novel combinations of ARVs. All of the currently approved HIV antiretrovirals have been implicated in causing long-term toxicities; however the greatest body of evidence for long-term metabolic effects has implicated the nucleoside reverse transcriptase (NRTI) class. By utilizing a non-NRTI treatment regimen, it is hypothesized that many of these long-term metabolic effects (renal toxicity, bone loss, body fat changes) can be delayed or avoided altogether. The clinical data on novel combinations is currently limited but rapidly growing and has included several combinations that have utilized darunavir. This study will be the first of its kind using the unique combination of darunavir/cobicistat and rilpivirine. Currently, this drug combination is not a recommended option for first time treatment of HIV

NCT02404233 HIV Positive Drug: darunavir/cobicistat Drug: rilpivirine
MeSH: HIV Seropositivity

Exclusion Criteria 1. Patient with active AIDS-defining opportunistic infection or disease according to the 1993 CDC AIDS surveillance definition (Clinical Category C) in the 30 days prior to baseline and that, in the opinion of the investigator, would preclude the patient from participating in the study (See Appendix C). 2. Patient has none of the following darunavir-associated RAMs: V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V, L89V 3. Having documented genotypic evidence of NNRTI resistance at screening or from historical data available in the source documents, i.e. at least one of the NNRTI rams from the following list; K101E, K101P, E138A, E138G, E138K, E138R, E138Q, , V179L, Y181C, Y181I, Y181V, Y188L, H221Y, F227C, M230I, M230L, or the combination of the K103N and L100I. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- I54M --- --- T74P --- --- L76V --- --- I84V --- --- L89V --- --- K101E --- --- K101P --- --- E138A --- --- E138G --- --- E138K --- --- E138R --- --- E138Q --- --- V179L --- --- Y181C --- --- Y181I --- --- Y181V --- --- Y188L --- --- H221Y --- --- F227C --- --- M230I --- --- M230L --- --- K103N ---

Primary Outcomes

Measure: Proportion of patients with plasma HIV-1 RNA <50 copies/mL

Time: up to weeks 48

Secondary Outcomes

Measure: Proportion of patients with plasma HIV-1 RNA <400 copies/mL at each time point evaluated

Time: At week 4, week 12, week 24, week 36, week 48

Measure: Number of weeks until HIV RNA <400 copies/mL and <50 copies/mL, respectively

Time: At week 4, week 12, week 24

14 Comparing Type and Prevalence of HIV Drug Resistance in Treatment Experienced and naïve HIV-infected Adults in Uganda and Switzerland

The investigators aim to assess type and frequency of HIV drug resistance in adults presenting to the Infectious Diseases Institute (IDI) in Kampala, Uganda, and compare this data to patients from the Swiss HIV Cohort Study (SHCS). This study is a single-site, cross-sectional study. The Investigators' goal is to perform viral load measurements in 2750 HIV-infected patients who have been on ART for 6 months or more. Presuming a detectable viral load in 10%, resistance testing would then be performed in 250 patients on ART. All adult patients attending will be screened for enrollment. Furthermore, the investigators' goal is to perform resistance testing in 250 ART naive patients in order to detect transmitted resistance mutations. Investigators will therefore consecutively screen and enroll 250 ART naive patients who attend the clinic during the study period. For each participant, a case report form (CRF) form will be completed which includes social, as well as medical information. Investigators will ask each participant for permission to store plasma in case resistance testing must be repeated, and serum, in case of future research questions.

NCT02507921 HIV Drug Resistance

These analyses will be performed for all drug-resistance mutations pooled together (outcome-variable= patient has any drug resistance mutation), for drug resistance mutations against individual drug classes (outcome = patient has any drug resistance mutation to a particular drug class), and for the two resistance mutations (M184V and K103N) that have been most prevalent in previous studies in resource-limited settings. --- M184V --- --- K103N ---

Primary Outcomes

Description: Type and frequency of transmitted HIV drug resistance mutations detected in treatment naive patients and comparison to naive patients in the Swiss HIV Cohort Study (SHCS) • Identification of risk factors associated with the occurrence of transmitted HIV drug resistance mutations in treatment-naive patients

Measure: HIV drug resistance in treatment-naive patients

Time: up to 12hrs

Description: • Type and frequency of HIV drug resistance mutations detected in patients on ART with virological failure and comparison to patients on treatment the Swiss HIV Cohort Study (SHCS) Identification of risk factors associated with the detection of HIV drug resistance mutations in treatment-experienced patients

Measure: HIV drug resistance in treatment-experienced patients

Time: up to 12hrs

Secondary Outcomes

Description: Proportion of HIV-infected patients with detectable viral load in the absence of immunological and/or clinical treatment failure

Measure: Viroligical failure

Time: up to 12hrs

Description: • Diagnostic performance of immunological/clinical criteria for the detection of treatment failure compared to virological testing (gold standard)

Measure: Viroligical failure

Time: up to 12hrs

Description: •Type and frequency of HIV drug resistance mutations detected in ART naive and experienced patients in Uganda and comparison to migrants from sub-Saharan Africa in the SHCS

Measure: Viroligical failure

Time: up to 12hrs

Description: •Assessment of local risk factors for treatment failure

Measure: Viroligical failure

Time: up to 12hrs

15 A Phase IIa Multicenter, Open-Label Clinical Trial to Evaluate the Safety and Efficacy of MK-1439A in Treatment-Naïve HIV-1 Infected Subjects With Selected Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Transmitted Resistance Mutations

The primary objectives of this study are to evaluate the antiretroviral activity and to evaluate the safety and tolerability of open-label MK-1439A consisting of a single fixed-dose combination (FDC) tablet of MK-1439 100 mg/lamivudine 300 mg/tenofovir disoproxil fumarate 300 mg in treatment-naive HIV-1 infected participants with selected NNRTI transmitted resistance mutations.

NCT02629822 HIV-1 Infection Drug: MK-1439A

- Prior to screening, have had a genotype performed confirming the presence of only one of the following NNRTI mutations: K103N, Y181C, or G190A. --- K103N ---

Primary Outcomes

Description: The percentage of participants achieving HIV-1 ribonucleic acid (RNA) <50 copies/mL in plasma at Week 48 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 48 visit.

Measure: Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 48

Time: Week 48

Description: The percentage of participants experiencing ≥1 AE up to Week 48 was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Measure: Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 48

Time: Up to Week 48

Description: The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Measure: Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 48.

Time: Up to Week 48

Description: The percentage of participants experiencing ≥1 AE up to Week 96 was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Measure: Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 96

Time: Up to Week 96

Description: The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined.

Measure: Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 96

Time: Up to Week 96

Secondary Outcomes

Description: The percentage of participants achieving HIV-1 ribonucleic acid (RNA) <50 copies/mL in plasma at Week 96 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 96 visit.

Measure: Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 96

Time: Week 96

Description: The percentage of participants achieving HIV-1 ribonucleic acid (RNA) <40 copies/mL in plasma at Week 48 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 48 visit. Participants with reading below the LoQ were considered to have <40 copies/mL.

Measure: Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 48

Time: Week 48

Description: The percentage of participants achieving HIV-1 ribonucleic acid (RNA) <40 copies/mL in plasma at Week 96 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 96 visit. Participants with reading below the LoQ were considered to have <40 copies/mL.

Measure: Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 96

Time: Week 96

Description: The change from baseline in CD4 cell count at Week 48 was calculated.

Measure: Change From Baseline in CD4 Cell Count at Week 48

Time: Baseline (Day 1) and Week 48

Description: The change from baseline in CD4 cell count at Week 96 was calculated.

Measure: Change From Baseline in CD4 Cell Count at Week 96

Time: Baseline (Day 1) and Week 96

Description: The time to loss of virologic response (TLOVR) was reported. For participants who achieved HIV-1 RNA <50 copies/mL of plasma and subsequently had two consecutive HIV-1 RNA values of ≥50 copies/mL measured at least 1 week apart, TLOVR was the time between Day 1 and the date of the first of the two consecutive values ≥50 copies/mL. For participants who achieved and sustained HIV-1 RNA <50 copies/mL, time to loss of virologic response was censored at the time of the last available measurement.

Measure: Time to Loss of Virologic Response

Time: Up to Week 96

16 A Phase III, Randomized, Multicenter, Parallel-group, Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Long-Acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor Single Tablet Regimen in HIV-1 Infected Antiretroviral Therapy Naive Adult Participants

The First Long-Acting Injectable Regimen (FLAIR) study is being conducted to establish if human immunodeficiency virus type-1 (HIV-1) infected adult participants whose virus is virologically suppressed on an integrase inhibitor single tablet regimen (INI STR) will remain suppressed after switching to a two-drug intramuscular (IM) long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In this study, the INI STR will be limited to abacavir/dolutegravir/lamivudine (ABC/DTG/3TC). FLAIR is a Phase 3, multi-phase, randomized, open label, active-controlled, multicenter, parallel-group, non-inferiority study in HIV-1, anti-retroviral therapy (ART)-naïve adult participants. This study is designed to demonstrate the non-inferior antiviral activity of switching to a two drug CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks (Q4W: monthly) compared to remaining on ABC/DTG/3TC over 48 weeks (4 weeks oral CAB + RPV, 44 weeks LA therapy). Participants who are HLA-B*5701 positive at Screening may enroll into the study and receive DTG plus a non-abacavir containing dual nucleoside reverse transcriptase inhibitor (NRTI) regimen. Eligible participants will enroll into the Induction Phase of the study and receive ABC/DTG/3TC for 20 weeks (Week [-20] to Day 1). Participants who have an HIV 1 ribose nucleic acid (RNA) <50 copies per milliliter (c/mL) at Week (-4) will be randomized (1:1) into the Maintenance Phase at Day 1 to either continue ABC/DTG/3TC or to discontinue ABC/DTG/3TC and begin oral therapy with CAB 30 mg + RPV 25 mg once daily for approximately 4 Weeks, followed by monthly CAB LA + RPV LA injections from visit Week 4b until study completion or withdrawal. Participants who successfully complete Week 100 (without meeting study defined withdrawal criteria and who remain virologically suppressed through Week 96: HIV-1 RNA <50 c/mL) will be given the option to switch to the LA arm in the Extension Phase (using an optional oral lead-in with CAB + RPV) or be withdrawn from the study. Participants will continue to receive injections every 4 weeks during the Extension Phase until CAB LA and RPV LA are either locally approved and commercially available, the participant no longer derives clinical benefit, the participant meets a protocol-defined reason for discontinuation, or until development of either CAB LA or RPV LA is terminated.

NCT02938520 HIV Infections Drug: Cabotegravir (CAB) tablet Drug: Rilpivirine (RPV) tablet Drug: Cabotegravir - Injectable Suspension (CAB LA) Drug: Rilpivirine - Injectable Suspension (RPV LA) Drug: ABC/DTG/3TC STR - Tablet Drug: DTG Tablet
MeSH: HIV Infections

- Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 within 28 days of the first dose of IP. - Use of medications which are associated with Torsades de Pointes - Any evidence of primary resistance to non-nuclease reverse transcriptase inhibitors (NNRTIs) (except for K103N which is allowed), or any known resistance to INIs from historical resistance test results. --- K103N ---

Primary Outcomes

Description: Percentage of participants with virologic failure endpoint (HIV-1 RNA>=50 c/mL) as per Food and Drug Administration (FDA) snapshot algorithm at Week 48 was assessed to demonstrate the noninferior antiviral activity of switching to intramuscular (IM) CAB LA+RPV LA every 4 weeks compared to continuation of ABC/DTG/3TC regimen over 48 weeks in HIV-1 infected ARTexperienced participants. The HIV-1 RNA >=50 copies/mL per snapshot algorithm was determined by the last on-treatment HIV-1 RNA measurement within the Week 48 analysis visit window (+/- 6 weeks) or at time of discontinuation (if discontinuation occurred prior to Week 48 for reasons other than Adverse Event).

Measure: Percentage of Participants With Virologic Failure (HIV-1 Ribonucleic Acid [RNA] >=50 Copies Per Millilter [mL]) Using Snapshot Algorithm at Week 48

Time: Week 48

Secondary Outcomes

Description: Percentage of participants with plasma HIV-1 RNA <50 copies/mL at Week 48 using FDA snapshot algorithm was assessed to demonstrate antiviral and immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to continuation of ABC/DTG/3TC. The HIV-1 RNA <50 copies/mL per snapshot algorithm was determined by last on-treatment HIV-1 RNA measurement within the Week 48 analysis visit window (+/- 6 weeks). Participants with no data in the analysis window were classificated as non-responders.

Measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL Using Snapshot Algorithm at Week 48

Time: Week 48

Description: Percentage of participants with plasma HIV-1 RNA <200 copies/mL at Week 48 using the snapshot algorithm was assessed based on the antiviral and immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to continuation of ABC/DTG/3TC

Measure: Number of Participants With HIV-1 RNA <200 Copies/mL Using Snapshot Algorithm at Week 48

Time: Week 48

Description: The CVF is defined as rebound as indicated by two consecutive plasma HIV-1-RNA levels >=200 copies/mL after prior suppression to <200 copies/mL.

Measure: Number of Participants With Confirmed Virologic Failure (CVF) During the Maintenance Phase

Time: Week 48

Description: Plasma for quantitative HIV-1 RNA were collected at indicated time points. Logarithm to base 10 (log10) values for plasma HIV-1 RNA has been presented.

Measure: Absolute Values for Plasma HIV-1 RNA at Week 48

Time: Week 48

Description: Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline was defined as: HIV-1 RNA(log 10) at Week 48 minus HIV-1 RNA(log 10) at Baseline.

Measure: Change From Baseline Values for Plasma HIV-1 RNA at Week 48

Time: Baseline (Day 1) and at Week 48

Description: Blood samples were collected and CD4+ cell count assessment by flow cyclometry was carried out to evaluate the immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to ABC/DTG/3TC

Measure: Absolute Values for CD4+ Lymphocyte Count at Week 48

Time: Week 48

Description: Blood samples were collected and CD4+ cell count assessment by flow cyclometry was carried out to evaluate the immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to ABC/DTG/3TC. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline was defined as post-dose visit value at Week 48 minus Maintenance Baseline value.

Measure: Change From Baseline Values for CD4+ Lymphocyte Count at Week 48

Time: Baseline (Day 1) and Week 48

Description: Data for participants who experienced disease progression to Centers for Disease Control and Prevention (CDC) Stage III or death has been presented. CDC stage is derived according to lowest post baseline CD4+ T-lympohocyte count and/or occurrence of AIDS-defining conditons (per 2014 CDC criteria).

Measure: Number of Participants With Disease Progression

Time: Day 1 up to an average of 59 weeks

Description: An AE is any untoward medical occurrence temporally associated with the use of a study treatment, whether or not considered related to study treatment. A SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment. Safety Population: all randomized participants who received at least 1 dose of IP during maintenance phase and assessed according to actual treatment received. All Maintenance Phase AEs was presented including AEs with start date occurring on/after date of 1st dose of randomized treatment, up to and including start date of LTFU antiretroviral therapy for participants who discontinued from Q4W arm. Non-SAE counts in >=5% of participants within any arm is reported

Measure: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

Time: Day 1 up to an average of 59 Weeks

Description: Severity of adverse events (AEs) were defined as per The Division of acquired immuno deficiency syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table) Version 2.0, November 2014. Severity grades for AEs were as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Potentially life-threatening) and Grade 5 were all deaths related to an AE. All Maintenance Phase adverse events have been presented, which includes AEs with start date occuring on or after the date of first dose of randomized study treatment, up to and including the start date of LTFU antiretroviral therapy for participants who discontinued from the Q4W arm.

Measure: Number of Participants With Severity of Adverse Events

Time: Up to Week 48

Description: Blood samples were collected for the analysis of hematology parameters including basophil, eosinophils, leukocytes, lymphocytes, neutrophils, monocytes, and platelets at indicated time points.

Measure: Absolute Values for Hematology Parameters Over Time Including Week 48: Basophils, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameter including erythrocyte mean corpuscular volume at indicated timepoints.

Measure: Absolute Values for Hematology Parameters Over Time Including Week 48: Erythrocyte Mean Corpuscular Volume

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameters including erythrocytes at indicated timepoints.

Measure: Absolute Values for Hematology Parameters Over Time Including Week 48: Erythrocytes

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated timepoints.

Measure: Absolute Values for Hematology Parameters Over Time Including Week 48: Hemoglobin

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameters including hematocrit at indicated timepoints.

Measure: Absolute Values for Hematology Parameters Over Time Including Week 48: Hematocrit

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CK at indicated timepoints.

Measure: Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatinine Kinase (CK)

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-albumin at indicated timepoints.

Measure: Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin at indicated timepoints.

Measure: Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters which includes total CO2, chloride, glucose, phosphate, potassium, sodium and urea at indicated timepoints.

Measure: Absolute Values for Clinical Chemistry Parameters: Total Carbon-dioxide (CO2), Chloride, Glucose, Phosphate, Potassium, Sodium and Urea Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-lipase at indicated timepoints.

Measure: Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-creatinine clearance at indicated timepoints. Glomerular filtration rate (GFR) will be estimated by the central laboratory using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).

Measure: Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance.

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected at Baseline and at Week 48 to assess fasting lipids which included total cholesterol, high density lipoprotein (HDL)cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides.

Measure: Absolute Values for Fasting Lipid Panel Overtime Including Week 48

Time: Baseline (Day 1) and at Week 48

Description: The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters (ketones, glucose, bilirubin, occult blood, nitrite and blood protein) can be read as positive, trace, 1+, 2+, 3+ and 4+ indicating proportional concentrations in the urine sample. The urine parameters were graded according to DAIDS scale where Grade 1 indicates mild (trace to 1+), Grade 2 indicates moderate (2+) and Grade 3 indicates severe (3+ or higher). Only participants with abnormal findings for urinalysis at any visit has been presented.

Measure: Number of Participants With Abnormal Urinalysis Parameter Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0).

Measure: Number of Participants With Urine Potential of Hydrogen (pH) Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: Blood samples were collected for the analysis of hematology parameters including basophil, eosinophils, leukocytes, lymphocytes, neutrophils, monocytes, and platelets at indicated timepoints. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline was defined as post-dose visit value minus Baseline value.

Measure: Change From Baseline for Hematology Parameters: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameter including erythrocyte mean corpuscular volume at indicated timepoints. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance phase dose of IP. Change from Baseline was defined as post-dose visit value minus Baseline value.

Measure: Change From Baseline for Hematology Parameters: Erythrocyte Mean Corpuscular Volume

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameters including erythrocytes at indicated timepoints. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance phase dose of IP. Change from Baseline was defined as post-dose visit value minus Baseline value.

Measure: Change From Baseline for Hematology Parameters: Erythrocytes

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameters including hematocrit at indicated timepoints. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance phase dose of IP. Change from Baseline was defined as post-dose visit value minus Baseline value.

Measure: Change From Baseline for Hematology Parameters: Hematocrit

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated timepoints. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.

Measure: Change From Baseline for Hematology Parameters: Hemoglobin

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CK. Baseline values is defined as the latest pre-treatment assessment with a non-missing value. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline in Clinical Chemistry Parameters Over Time Including Week 48: ALT, ALP, AST and CK

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-albumin. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters which includes total CO2, chloride, glucose, phosphate, potassium, sodium and urea. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-lipase. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-creatinine clearance. GFR will be estimated by the central laboratory using the CKD-EPI. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected at Baseline and at Week 48 to assess glucose and fasting lipids which included total cholesterol, high density lipoprotein (HDL)cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides. Only fasting data is presented for glucose and lipids. Baseline value is defined as the last available fasting recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at Week 48 visit (if collected while fasting) minus the Baseline value.

Measure: Change From Baseline Values for Fasting Lipid Panel and Glucose Overtime Including Week 48

Time: Baseline (Day 1) and at Week 48

Description: Urine biomarker samples were collected for the analysis of urine albumin/creatinine ratio and urine protein/creatinine ratio. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: Urine biomarker samples were collected for the analysis of urine creatinine. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values in Urine Creatinine Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: Urine biomarker samples were collected for the analysis of urine phosphate. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values in Urine Phosphate Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: Urine biomarker samples were collected for the analysis of urine retinol binding protein. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values in Urine Retinol Binding Protein Over Time Including Week 48

Time: Baseline (Day 1) and at Week 48

Description: Urine biomarker samples were collected for the analysis of urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. The urine specific gravity was measured as the ratio of urine density compared with water density.

Measure: Change From Baseline Values in Urine Specific Gravity Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). Baseline value is defined as the last available recorded value up to and including the date of first Maintenance Phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values in Urine pH Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. All Maintenance Phase adverse events (start date occurring on or after the date of first dose of randomized study treatment) leading to withdrawal have been presented.

Measure: Number of Participants Who Discontinued or Withdrawn Due to AEs Over Time Including Week 48

Time: Up to Week 48

Description: Blood samples were collected at Baseline and at Week 48 to assess fasting lipids which included total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Baseline value is defined as the last available recorded fasting value up to and including the date of first Maintenance Phase dose of IP. Percentage change from baseline is calculated as: value at Week 48 (if collected while fasting) minus Baseline value divided by Baseline value multiplied by 100.

Measure: Percentage Change From Baseline in Fasting Lipids Overtime Including Week 48

Time: Baseline (Day 1) and at Week 48

Description: Plasma samples were collected and analyzed from participants who met confirmed virologic withdrawal criteria. Phenotypic Resistance data for following drugs :CAB,dolutegravir(DTG),elvitegravir (EVG), raltegravir(RAL),delavirdine(DLV),efavirenz(EFV),etravirine(ETR),nevirapine(NVP),RPV,lamivudine(3TC),abacavir(ABC),emtricitabine(FTC),tenofovir(TDF),zidovudine(ZDV),stavudine(d4T),didanosine(ddI),atazanavir(ATV),darunavir(DRV),fosamprenavir(FPV),indinavir(IDV),lopinavir(LPV),nelfinavir(NFV),ritonavir(RTV), saquinavir(SQV) and tipranavir (TPV) in participants meeting CVF criteria is presented.Phenotypic resistance, partially sensitive, and Sensitive were defined based on fold change(FC) value from Monogram as:resistance (FC>clinical higher cutoff/biologic cutoff),partially sensitive (FC=clinical higher cutoff and > clinical lower cutoff),sensitive(FC<=clinical lower cutoff/biologic cutoff). The CVF population comprised of all participants in ITT-E population who met CVF criteria

Measure: Number of Participants With Phenotypic Resistance Through Week 48

Time: Week 48

Description: Plasma samples were collected and analyzed from participants who met confirmed virologic withdrawal criteria. Genotypic Resistance data for the following drugs: DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV, DRV, FPV, IDV, LPV, NFV, RTV, SQV and TPV in participants meeting CVF criteria has been presented.

Measure: Number of Participants With Genotypic Resistance Through Week 48

Time: Week 48

Description: AUC values are Bayesian pharmacokinetic (PK) parameter estimates obtained from a population PK meta-analysis of the data collected from studies 201584 and 201585# NCT02951052. Blood samples from the current study 201584 were collected at indicated time points to analyse concentration in plasma for CAB LA. The PK Population includes all participants who received CAB and / or RPV and undergo PK sampling during the study, and provide CAB and /or RPV plasma concentration data.

Measure: Area Under the Curve (AUC) for CAB LA

Time: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5, 41, 2 hours post-dose at Weeks 4 and 48

Description: AUC values are Bayesian PK parameter estimates obtained from a population PK meta-analysis of the data collected from studies 201584 and 201585# NCT02951052. Blood samples from the current study 201584 were collected at indicated time points to analyse concentration in plasma for RPV LA

Measure: AUC for RPV LA

Time: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5, 41, 2 hours post-dose at Weeks 4 and 48

Description: Blood samples were collected at indicated time points for PK analysis of CAB LA.

Measure: Plasma Trough Concentration (Ctrough) for CAB LA Evaluable

Time: Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected at indicated time points for PK analysis of RPV LA.

Measure: Ctrough for RPV LA Evaluable

Time: Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples will be collected at indicated time points for PK analysis of CAB LA.

Measure: Maximum Concentration (Cmax) in Plasma for CAB LA Evaluable at Week 41

Time: Week 41- 1 Week post dose

Description: Blood samples will be collected at indicated time points for PK analysis of RPV LA.

Measure: Cmax in Plasma for RPV LA Evaluable at Week 41

Time: Week 41- 1 Week post dose

Description: Blood samples were planned to be collected at indicated time points for PK analysis of CAB LA and RPV LA. Demographic parameters including, but not limited to, age, sex, race, body weight, body mass index, and relevant laboratory parameters were planned to be evaluated as potential predictors of inter subject variability for pharmacokinetic parameters.

Measure: Number of Participants With Different Demographic Parameters for Inter-subject Variability

Time: Up to Week 48

Description: PIN questionnaire explores bother of pain at injection site and injection site reactions (ISR),anxiety before and after injection, willingness to receive HIV injectable treatment and satisfaction with mode of treatment administration of individuals receiving injection and perceptions associated with receiving injections.This measure contains 21 items: pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside clinical trial. Scores range from 1 to 5; questions are phrased to ensure that 1:most favorable perception of vaccination, and 5:most unfavorable.Dimension scores include bother from ISR, leg movement, sleep and acceptability.Score of a domain is calculated as mean of all items with domain.Higher scores represent worse perception of injection.LOCF was primary method of analysis

Measure: Change From Week 5 in Dimension Scores Using Perception of Injection Questionnaire (PIN)-Last Observation Carried Forward (LOCF)

Time: Weeks 5 and at Weeks 41 and 48

Description: PIN questionnaire explores bother of pain at injection site and injection site reactions (ISR),anxiety before and after injection, willingness to receive HIV injectable treatment, following visit and satisfaction with mode of treatment administration of individuals receiving injection and perceptions associated with receiving injections.This measure contains 21 items: pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside clinical trial. Scores range from 1 to 5; questions are phrased to ensure that 1:most favorable perception of vaccination, and 5:most unfavorable.Dimension scores include bother from ISR, leg movement, sleep and acceptability.Score of a domain is calculated as mean of all items with domain.Higher scores represent worse perception of injection.LOCF was primary method of analysis.

Measure: Percentage of Participants With Extremely or Very Acceptable Pain and Local Reaction: Acceptability Score on PIN Questionnaire

Time: Weeks 5, 41 and 48

Description: The HATQoL questionnaire was used to assess health related QoL (HRQoL). It comprises of three dimensions: life satisfaction (LISAT), medication worries (MEDWO) and disclosure worries (DISWO). For LISAT domain, each question is scored as 1-5, where 5 corresponds to satisfaction 'all of time' and 1 as 'none of time'. Total score for the LISAT domain (sum of item scores for questions 1a to 1d) is transformed to a 0-100 scale using formula:[100 divided by (20 minus 4)]*(raw total score for LISAT minus 4). Higher the LISAT score, greater satisfaction to life. Transformed dimension score for each domain was summarized and analyzed. LOCF was used as primary method of analysis. Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI. Baseline value is defined as the last available value up to and including the date of first Maintenance phase dose of IP. Change from Baseline value is calculated as value at post-dose visit minus Baseline value.

Measure: Change From Baseline in Life Satisfaction (LISAT) Using HIV/AIDs-targeted Quality of Life (HATQoL) Questionnaire

Time: Baseline (Day 1) and at Weeks 24 and 48

Description: The HATQoL questionnaire was used to assess HRQoL. It comprises of three dimensions: LISAT, MEDWO and DISWO. For the MEDWO domain, each question is scored as 1-5, where 5 is associated with medication worry 'none of the time' and 1 as 'all of the time'. The total score for the MEDWO domain (sum of item scores for questions 2a to 3e) is transformed to a 0-100 scale using formula: [100 divided by (25 minus 5)]* (raw total score for MEDWO minus 5). Higher MEDWO scores correspond to lower medication worries. Transformed dimension score for each domain was summarized and analyzed. LOCF was used as primary method of analysis. Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI. Baseline value is defined as the last available value up to and including the date of first Maintenance phase dose of IP. Change from Baseline value is calculated as value at post-dose visit minus Baseline value.

Measure: Change From Baseline in HIV Medication, MEDWO Using HATQoL

Time: Baseline and at Weeks 24 and 48

Description: The HATQoL questionnaire was used to assess HRQoL. It comprises of three dimensions: LISAT, MEDWO and DISWO. For the DISWO domain, each question is scored as 1-5, where 5 is associated with disclosure worry 'none of the time' and 1 as 'all of the time'. The total score for the DISWO domain (sum of item scores for questions 3a to 3e) is transformed to a 0-100 scale using formula: [100 divided by (25 minus 5)]* (raw total score for DISWO minus 5). Higher DISWO total scores correspond to lower disclosure worries. Transformed dimension score for each domain was summarized and analyzed. LOCF was used as primary method of analysis. Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI. Baseline value is defined as the last available value up to and including the date of first Maintenance phase dose of IP. Change from Baseline value is calculated as value at post-dose visit minus Baseline value.

Measure: Change From Baseline in DISWO Using HATQoL

Time: Baseline and at Weeks 24 and 48

Description: The SF-12 questionnaire consists of 7 questions which measures degree of general health status and mental health distress. Each question is scored 0-5, except for question 2 scored 0-3. HRQoL using SF-12 for physical component summary (PCS) and mental component summary (MCS) were assessed for two treatment groups.Missing component scores was imputed using LOCF.PCS/MCS are calculated using computer software purchased from QualityMetric (http://www.qualitymetric.com).The higher the score, the better will be the health status.Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI. Baseline value is defined as the last available recorded value up to and including the date of first Maintenance phase dose of IP. Change from Baseline value is calculated as value at post-dose visit minus Baseline value.

Measure: Change From Baseline in Health Status Using 12-item Short Form Survey (SF-12)

Time: Baseline and at Weeks 24 and 48

Description: HIVTSQs (status version) total treatment satisfaction score is computed with 1-11 items. Items 1-11 are summed to produce score with possible range of 0 to 66. Higher the score, greater improvement in satisfaction with treatment; lower score, greater the deterioration in satisfaction with treatment. A score of 0 represents no change. LOCF was primary method of analysis. Baseline value is defined as the last available value up to and including the date of first Maintenance phase dose of IP. Change from Baseline value is calculated as value at post-dose visit minus Baseline value. Adjusted mean and 95% CI of adjusted mean values has been presented.

Measure: Change From Baseline in Total Treatment Satisfaction Using HIV Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4b, 24 and 44

Time: Baseline and at Weeks 4b, 24 and 44

Description: HIVTSQc (change version) total treatment satisfaction score is computed with 1-11 items. Items 1-11 are summed to produce score with possible range:-33 to 33. Higher scores represent greater improvement in treatment satisfaction compared to satisfaction with treatment received during the induction phase; lower scores representedeterioration in satisfaction with treatment. A score of 0 represents no change. LOCF was primary method of analysis. Baseline value is defined as the last available value up to and including the date of first Maintenance phase dose of IP. Change from Baseline value is calculated as value at post-dose visit minus Baseline value.

Measure: Change in Treatment Satisfaction Over Time Using HIVTSQc at Week 48

Time: Week 48

Description: HIVTSQs (status version) is a 12 item questionnaire. The individual item scores are ratedas 6 (very satisfied, convenient, flexible, etc.) to 0 (very dissatisfied, inconvenient, inflexible, etc.). Higher scores represent greater treatment satisfaction as compared to the past few weeks. LOCF was used as primary method of analysis. Baseline value is defined as the last available value up to and including the date of first Maintenance phase dose of IP. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline in Individual Item Scores of HIVTSQs at Weeks 4b, 24 and 44

Time: Baseline and at Weeks 4b, 24 and 44

Description: ACCEPT questionnaire is generic medication acceptance measure assessing how participants weigh advantages and disadvantages of long-term medication. It consists 25 items, capturing six dimensions. 3 questions focusing on general acceptance of study medication were analyzed. Items scores are rated as 1-5 :1-totally disagree,2-somewhat disagree,3-somewhat agree,4-totally agree and 5-I don't know. The acceptance domain score (ranging from 0 to 100) is calculated using the following formula:100*(mean of recoded items in dimension minus 1) divided by 2.LOCF was primary method of analysis. Measure type is mean for adjusted mean and dispersion measure: 95% CI. Baseline value is defined as the last available value up to and including the date of first Maintenance phase dose of IP. Change from Baseline value is calculated as value at post-dose visit minus Baseline value.

Measure: Change From Baseline in Treatment Acceptance at Weeks 8, 24 and 48 Using "General Acceptance" Dimension of the Chronic Treatment Acceptance (ACCEPT) Questionnaire

Time: Baseline and at Weeks 8, 24 and 48

Description: The NRS questionnaire is used to assess the tolerability of injections in CAB LA+RPV LA arm only. The questionnaire consists of one single question and will assess maximum level of pain experienced with the most recent injections ranking from no pain (0) to extreme pain (10). Missing scores was imputed using LOCF.

Measure: Change From 4b in Tolerability of Injection at Weeks 5, 40 and 41 Using Numeric Rating Scale (NRS) Within CAB LA+RPV LA Arm

Time: Weeks 4b, 5, 40 and 41

17 A Phase III, Randomized, Multicenter, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current INI- NNRTI-, or PI-based Antiretroviral Regimen in HIV-1-infected Adults Who Are Virologically Suppressed

The Antiretroviral Therapy as Long Acting Suppression (ATLAS) study is being conducted to establish if human immunodeficiency virus type-1 (HIV-1) infected adult subjects with current viral suppression on a regimen with 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a third agent, remain suppressed upon switching to a two-drug intramuscular (IM) long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). This is a Phase 3, multi-phase, randomized, open label, active-controlled, multicenter, parallel-group, non-inferiority study in HIV-1, antiretroviral therapy (ART)-adult subjects who are stably suppressed on a current antiretroviral (ARV) regimen. This study is designed to demonstrate the non-inferior antiviral activity of switching to a two drug CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks (Q4W: monthly) compared with maintenance of current ARV regimen containing 2 NRTIs plus an INI, NNRTI, or a PI. Eligible subjects will be randomized (1:1) into the Maintenance Phase at Day 1 to either continue current ART or switch to initiate oral therapy with CAB 30 mg + RPV 25 mg once daily for 4 Weeks followed by Q4 weekly (monthly) CAB LA + RPV LA injections. Following the Maintenance phase at Week 52, subjects who were randomized to continue their current ART regimen will be given an option to switch to CAB LA + RPV LA injections. Those subjects would transition to LA dosing, beginning with 4 weeks oral CAB + RPV therapy at Week 52, and receive the first IM CAB LA + RPV LA injections at Week 56.

NCT02951052 Infection, Human Immunodeficiency Virus HIV Infections Drug: Cabotegravir (CAB) tablet Drug: Rilpivirine (RPV) tablet Drug: Cabotegravir - Injectable Suspension (CAB LA) Drug: Rilpivirine - Injectable Suspension (RPV LA) Drug: 2 NRTIs plus an INI, NNRTI, or PI
MeSH: Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome

- Any evidence of primary resistance based on the presence of any major known INI or NNRTI resistance-associated mutation, except for K103N, (International AIDS Society [IAS]-USA, 2015) by any historical resistance test result. --- K103N ---

Primary Outcomes

Description: Number of participants with virologic failure endpoint (HIV-1 RNA>=50 c/mL) as per Food and Drug Administration (FDA) snapshot algorithm at Week 48 was assessed to demonstrate the non-inferior antiviral activity of switching to intramuscular (IM) CAB LA+RPV LA every 4 weeks compared to continuation of current ART regimen over 48 weeks in HIV-1 infected ART-experienced participants. The HIV-1 RNA >=50 copies/mL per snapshot algorithm was determined by the last available on-treatment HIV-1 RNA measurement within the analysis visit window of interest.

Measure: Number of Participants With Virologic Failure (HIV-1 Ribonucleic Acid [RNA] >=50 Copies Per Millilter [mL]) Using Snapshot Algorithm at Week 48

Time: Week 48

Secondary Outcomes

Description: Plasma samples were collected for quantitative analysis of HIV-1 RNA. Number of participants with plasma HIV-1 RNA <50 copies/mL at Week 48 using FDA snapshot algorithm was assessed to demonstrate antiviral and immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to continuation of current ART. The HIV-1 RNA <50 copies/mL per snapshot algorithm was determined by the last available on-treatment HIV-1 RNA measurement within the analysis visit window of interest.

Measure: Number of Participants With HIV-1 RNA <50 Copies/mL Using Snapshot Algorithm at Week 48

Time: Week 48

Description: Number of participants with plasma HIV-1 RNA <200 copies/mL at Week 48 using the snapshot algorithm was assessed based on the antiviral and immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to continuation of current ART.

Measure: Number of Participants With HIV-1 RNA <200 Copies/mL Using Snapshot Algorithm at Week 48

Time: Week 48

Description: The CVF is defined as rebound as indicated by two consecutive plasma HIV-1-RNA levels >=200 copies/mL after prior suppression to <200 copies/mL. The outcome displays only visits during which at least one new CVF occurs. Plasma samples were collected for quantitative analysis of HIV-1 RNA.

Measure: Number of Participants With Confirmed Virologic Failure (CVF)

Time: Weeks 8, 12, 20, 24, 32 and 40

Description: Logarithm to base 10 (log10) values for plasma HIV-1 RNA has been presented.

Measure: Absolute Values for Plasma HIV-1 RNA at Week 48

Time: Week 48

Description: Plasma for quantitative HIV-1 RNA were collected at indicated time points. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as: HIV-1 RNA(log 10) at Week 48 - HIV-1 RNA(log 10) at Baseline.

Measure: Change From Baseline Values for Plasma HIV-1 RNA

Time: Baseline and Week 48

Description: Blood samples were collected and CD4+ cell count assessment by flow cyclometry was carried out to evaluate the immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to current ART.

Measure: Absolute Values for CD4+ Lymphocyte Count at Week 48

Time: Week 48

Description: Blood samples were collected and CD4+ cell count assessment by flow cyclometry was carried out to evaluate the immunologic activity of switching to IM CAB LA+RPV LA every 4 weeks compared to current ART.Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value at Week 48 minus Baseline value.

Measure: Change From Baseline Values for CD4+ Lymphocyte Count at Week 48

Time: Baseline (Day 1) and Week 48

Description: Disease progression was defined as HIV-associated conditions, acquired immunodeficiency syndrome (AIDS), and death through 48 Weeks. Data of participants who experienced disease progression to Centers for Disease Control and Prevention (CDC) Stage III or death has been presented.

Measure: Number of Participants With Disease Progression

Time: Up to Week 48

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. Safety Population comprised of all randomized participants who received at least one dose of IP during the maintenance phase of the study (on or after Day 1 visit). Participants will be assessed according to actual treatment received.

Measure: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

Time: Up to Week 48

Description: Severity of adverse events (AEs) were defined as per The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table) Version 2.0, November 2014. Severity grades for AEs were as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Potentially life-threatening) and Grade 5 were all deaths related to an AE.

Measure: Number of Participants With Severity of Adverse Events

Time: Up to Week 48

Description: Blood samples were collected for the analysis of hematology parameters including basophil, eosinophils, leukocytes, lymphocytes, neutrophils, monocytes, and platelets at indicated time points.

Measure: Absolute Values for Hematology Parameters Over Time Including Week 48: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameter including erythrocyte mean corpuscular volume at indicated time points.

Measure: Absolute Values for Hematology Parameters: Erythrocyte Mean Corpuscular Volume

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameters including erythrocytes at indicated time points.

Measure: Absolute Values for Hematology Parameters: Erythrocytes

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated time points.

Measure: Absolute Values for Hematology Parameters: Hemoglobin

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameters including hematocrit at indicated time points.

Measure: Absolute Values for Hematology Parameters: Hematocrit

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameters including basophil, eosinophils, leukocytes, lymphocytes, neutrophils, monocytes, and platelets at indicated timepoints. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.

Measure: Change From Baseline for Hematology Parameters: Basophil, Eosinophils, Leukocytes, Lymphocytes, Neutrophils, Monocytes, and Platelets

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameter including erythrocyte mean corpuscular volume at indicated timepoints. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.

Measure: Change From Baseline for Hematology Parameters: Erythrocyte Mean Corpuscular Volume

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameters including erythrocytes at indicated timepoints. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.

Measure: Change From Baseline for Hematology Parameters: Erythrocytes

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameters including hematocrit at indicated timepoints. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.

Measure: Change From Baseline for Hematology Parameters: Hematocrit

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated timepoints. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline was defined as post-dose visit value minus Baseline value.

Measure: Change From Baseline for Hematology Parameters: Hemoglobin

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CK at indicated time points.

Measure: Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) and Creatinine Kinase (CK)

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-albumin at indicated time points.

Measure: Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin at indicated time points.

Measure: Absolute Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters which includes total CO2, chloride, glucose, phosphate, potassium, sodium and urea at indicated time points.

Measure: Absolute Values for Clinical Chemistry Parameters: Total Carbon-dioxide (CO2), Chloride, Glucose, Phosphate, Potassium, Sodium and Urea Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-lipase at indicated time points.

Measure: Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-creatinine clearance at indicated timepoints. Glomerular filtration rate (GFR) will be estimated by the central laboratory using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).

Measure: Absolute Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters (ketones, glucose, bilirubin, occult blood, nitrite and blood protein) can be read as positive, trace, 1+, 2+, 3+ and 4+ indicating proportional concentrations in the urine sample. The urine parameters were graded according to Division of AIDS (DAIDS) scale where Grade 1 indicates mild (trace to 1+), Grade 2 indicates moderate (2+) and Grade 3 indicates severe (3+ or higher). Only participants with abnormal findings for urinalysis at any visit has been presented.

Measure: Number of Participants With Abnormal Urinalysis Parameters Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48.

Description: Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0).

Measure: Number of Participants With Urine Potential of Hydrogen (pH) Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CK. Baseline values is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline in Clinical Chemistry Parameters Over Time Including Week 48: ALT, ALP, AST and CK

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-albumin. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Albumin

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48: Bilirubin, Direct Bilirubin and Creatinine

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters which includes total CO2, chloride, glucose, phosphate, potassium, sodium and urea. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameters Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-lipase. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Lipase

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter-creatinine clearance. GFR will be estimated by the central laboratory using the CKD-EPI. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameter Over Time Including Week 48: Creatinine Clearance.

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of fasting lipid parameters- total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Fasting Lipid Panel Over Time Including Week 48

Time: Baseline (Day 1) and at Week 48

Description: Urine biomarker samples were collected for the analysis of urine albumin/creatinine ratio and urine protein/creatinine ratio.Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values in Urine Albumin/Creatinine Ratio and Urine Protein/Creatinine Ratio Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: Urine biomarker samples were collected for the analysis of urine creatinine. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values in Urine Creatinine Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: Urine biomarker samples were collected for the analysis of urine phosphate. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values in Urine Phosphate Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: Urine biomarker samples were collected for the analysis of urine retinol binding protein. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values in Urine Retinol Binding Protein Over Time Including Week 48

Time: Baseline (Day 1) and at Week 48

Description: Urine biomarker samples were collected for the analysis of urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The dipstick test gives results in a semi-quantitative manner. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. The urine specific gravity was measured as the ratio of urine density compared with water density.

Measure: Change From Baseline Values in Urine Specific Gravity Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). The dipstick test gives results in a semi-quantitative manner. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values in Urine pH Over Time Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 24 and 48

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

Measure: Number of Participants Who Discontinued or Withdrawn Due to AEs Over Time Including Week 48

Time: Up to Week 48

Description: Blood samples were collected at Baseline and at Week 48 to assess fasting lipids which included total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Percentage change from Baseline is calculated as: value at Week 48 minus Baseline value divided by Baseline value multiplied by 100.

Measure: Percentage Change From Baseline in Fasting Lipids Overtime Including Week 48

Time: Baseline (Day 1) and at Week 48

Description: Plasma samples were collected and analyzed from participants who met confirmed virologic withdrawal criteria.The CVF population comprised of all participants in ITT-E population who met CVF criteria.Phenotypic Resistance data for following drugs:CAB,dolutegravir(DTG),elvitegravir(EVG), raltegravir(RAL),delavirdine(DLV),efavirenz(EFV),etravirine(ETR),nevirapine(NVP),RPV,lamivudine(3TC),abacavir(ABC),emtricitabine(FTC),tenofovir(TDF),zidovudine(ZDV),stavudine(d4T),didanosine(ddI), atazanavir(ATV),darunavir(DRV),fosamprenavir(FPV),indinavir(IDV),lopinavir(LPV),nelfinavir(NFV),rito-navir(RTV),saquinavir(SQV) and tipranavir(TPV) in participants meeting CVF criteria is presented.Phenotypic resistance, partially sensitive, and Sensitive were defined based on fold change(FC) value from Monogram as:resistance(FC>clinical higher cutoff/biologic cutoff),partially sensitive(FC <=clinical higher cutoff and > clinical lower cutoff),sensitive(FC <= clinical lower cutoff/biologic cutoff).

Measure: Number of Participants With Phenotypic Resistance Through Week 48

Time: At the time of CVF

Description: Plasma samples were collected and analyzed from participants who met confirmed virologic withdrawal criteria. Genotypic Resistance data for the following drugs: DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV, DRV, FPV, IDV, LPV, NFV, RTV, SQV and TPV in participants meeting CVF criteria has been presented.

Measure: Number of Participants With Genotypic Resistance Through Week 48

Time: At the time of CVF

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

Measure: Number of Participants With AEs by Using Baseline Third Agent Treatment Class Overtime Including Week 48

Time: Up to Week 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).

Measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: ALT, ALP, AST and CK

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter: albumin to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).

Measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Albumin

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter: bilirubin, direct bilirubin and creatinine to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).

Measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Bilirubin, Direct Bilirubin and Creatinine

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter: creatinine clearance to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). GFR will be estimated by the central laboratory using the CKD-EPI.

Measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Creatinine Clearance

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter: lipase to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).

Measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Lipase

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters: CO2, chloride, glucose, phosphate, potassium, sodium and urea to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).

Measure: Absolute Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of fasting lipid panel: triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI).

Measure: Absolute Values for Fasting Lipid Panel Using Baseline Third Agent Treatment Class Overtime Including Week 48

Time: Baseline (Day 1) and at Week 48

Description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.

Measure: Number of Participants Discontinued or Withdrawn Due to AEs When Baseline Third Agent Treatment Class Was Used Over Time Including Week 48

Time: Up to Week 48

Description: Blood samples will be collected at indicated time points for pharmacokinetic (PK) analysis of CAB LA. PK population includes all participants who received CAB and / or RPV and underwent PK sampling during the study, and provided CAB and /or RPV plasma concentration data.

Measure: Plasma Trough Concentration (Ctrough) for CAB LA Evaluable

Time: Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples will be collected at indicated time points for PK analysis of RPV LA.

Measure: Ctrough for RPV LA Evaluable

Time: Pre-dose at Weeks 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: AUC values are Bayesian PK parameter estimates obtained from a population PK meta-analysis of the data collected from studies 201585 and 201584 # NCT02938520. Blood samples from the current study 201585 were collected at indicated time points to analyze concentration in plasma for CAB LA.

Measure: Area Under the Curve (AUC) for CAB LA

Time: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5 and 41

Description: AUC values are Bayesian PK parameter estimates obtained from a population PK meta-analysis of the data collected from studies 201585 and 201584 # NCT02938520. Blood samples from the current study 201585 were collected at indicated time points to analyze concentration in plasma for RPV LA.

Measure: AUC for RPV LA

Time: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48; 1 Week post-dose at Weeks 5 and 41

Description: Blood samples will be collected at indicated time points for PK analysis of CAB LA.

Measure: Maximum Concentration (Cmax) in Plasma for CAB LA Evaluable at Week 41

Time: Week 41- 1 Week post dose

Description: Blood samples will be collected at indicated time points for PK analysis of RPV LA.

Measure: Cmax in Plasma for RPV LA Evaluable at Week 41

Time: Week 41- 1 Week post dose

Description: Percentage of participants with virologic failure endpoint as per FDA snapshot algorithm at Week 48 was assessed based on the non-inferior antiviral activity of switching IM CAB LA+RPV LA every 4 weeks compared to continuation of current ART regimen over 48 weeks in HIV-1 infected ART-experienced participants. The HIV-RNA >=50 copies/mL per snapshot algorithm was determined using a Cochran-Mantel Haenszel test stratified by baseline third agent class: INI, NNRTI, or PI.

Measure: Percentage of Participants With a Virologic Failure Using Snapshot Algorithm by Baseline Third Agent

Time: Week 48

Description: Percentage of participants with HIV-1 RNA < 50copies/mL endpoint as per FDA snapshot algorithm at Week 48 was assessed based on the non-inferior antiviral activity of switching IM CAB LA+RPV LA every 4 weeks compared to continuation of current ART regimen over 48 weeks in HIV-1 infected ART-experienced participants. The HIV-RNA <50 copies/mL per snapshot algorithm was determined using a Cochran-Mantel Haenszel test stratified by baseline third agent class: INI, NNRTI, or PI.

Measure: Percentage of Participants With Plasma HIV-1 RNA <50copies/mL Using Snapshot Algorithm by Baseline Third Agent

Time: Week 48

Description: Severity of AEs were defined as per The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table). Severity grades for AEs were as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Potentially life-threatening) and Grade 5 were all deaths related to an AE.

Measure: Number of Participants With Severity of Adverse Events by Baseline Third Agents

Time: Up to Week 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters: ALT, ALP, AST and CK to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: ALT, ALP, AST and CK

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter: albumin to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Albumin

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter: bilirubin, direct bilirubin and creatinine to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Bilirubin, Direct Bilirubin and Creatinine

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter: creatinine clearance to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). GFR will be estimated by the central laboratory using the CKD-EPI. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Creatinine Clearance

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameter: lipase to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48: Lipase

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of clinical chemistry parameters: CO2, chloride, glucose, phosphate, potassium, sodium and urea to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Clinical Chemistry Parameters Using Baseline Third Agent Treatment Class Overtime Including Week 48

Time: Baseline (Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48

Description: Blood samples were collected for the analysis of fasting lipid panel: triglycerides, total cholesterol, HDL cholesterol and LDL cholesterol to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline Values for Fasting Lipid Panel Using Baseline Third Agent Treatment Class Overtime Including Week 48

Time: Baseline (Day 1) and at Week 48

Description: Plasma samples were collected from participants who met confirmed virologic withdrawal criteria to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Genotypic Resistance data for the following drugs: DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV, DRV, FPV, IDV, LPV, NFV, RTV, SQV and TPV in participants meeting CVF criteria has been presented.

Measure: Number of Participants With Genotypic Resistance Using Baseline Third Agent Through Week 48

Time: At the time of CVF

Description: Plasma samples were collected from participants who met confirmed virologic withdrawal criteria to assess the impact of Baseline third agent treatment class (PI, NNRTI and INI). Phenotypic Resistance data for the following drugs: CAB, DTG, EVG, RAL, DLV, EFV, ETR, NVP, RPV, 3TC, ABC, FTC, TDF, ZDV, d4T, ddI, ATV, DRV, FPV, IDV, LPV, NFV, RTV, SQV and TPV in participants meeting CVF criteria has been presented. Phenotypic resistance, partially sensitive, and Sensitive were defined based on FC value from Monogram as: resistance (FC>clinical higher cutoff/biologic cutoff), partially sensitive (FC <=clinical higher cutoff and > clinical lower cutoff), sensitive (FC <= clinical lower cutoff/biologic cutoff).

Measure: Number of Participants With Phenotypic Resistance Using Baseline Third Agent Through Week 48

Time: At the time of CVF

Description: The PIN questionnaire explores the bother of pain at the injection site and injection site reactions (ISR), anxiety before and after injection, willingness to receive an HIV injectable treatment the following visit and satisfaction with the mode of treatment administration of individuals receiving injection and perceptions of individuals associated with receiving injections.This measure contains 21 items that measure pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside of a clinical trial.Scores range from 1 to 5, and questions are phrased in such a way as to ensure that 1 always equated with the most favourable perception of vaccination, and 5 the most unfavourable.Dimension scores include bother from ISR, leg movement, sleep and acceptability.The score of a domain is calculated as the mean of all items with the domain.Higher scores represent worse perception of injection. LOCFwas used as primary method of analysis

Measure: Change From Week 5 in Dimension Scores Using Percerption of Injection Questionnaire (PIN)-Last Observation Carried Forward (LOCF) in Q4W Arm

Time: Week 5 and at Weeks 41 and 48

Description: The PIN questionnaire explores the bother of pain at the injection site and injection site reactions(ISR), anxiety before and after injection, willingness to receive an HIV injectable treatment the following visit and satisfaction with the mode of treatment administration of individuals receiving injection and perceptions of individuals associated with receiving injections.This measure contains 21 items that measure pain at injection site, local site reactions, impact on functioning and willingness to pursue injectable treatment outside of a clinical trial.Scores range from 1 to 5, and questions are phrased in such a way as to ensure that 1 always equated with the most favourable perception of vaccination, and 5 the most unfavourable.Dimension scores include bother from ISR, leg movement, sleep and acceptability.The score of a domain is calculated as the mean of all items with the domain.Higher scores represent worse perception of injection. LOCF was used as primary method of analysis

Measure: Percentage of Participants With Extremely or Very Acceptable Pain and Local Reaction: Acceptability Score on PIN Questionnaire in Q4W Arm

Time: Weeks 5, 41 and 48

Description: The HATQoL questionnaire was used to assess the health related QoL (HRQoL). It comprises of three dimensions: LISAT, medication worries (MEDWO) and disclosure worries (DISWO). The total imputed value score for LISAT is calculated on a 0-100 scale using the formula: LISAT 100=[100 divided by (20 minus 4)]*(LISAT minus 4). A response of 5 in LISAT score shows satisfaction all of the time and 1 as none of the time. The higher the score, the greater satisfaction to life and the less worry. The transformed dimension score for each domain was summarized and analyzed. LOCF was used as primary method of analysis. Measure type was considered as mean for adjusted mean and dispersion measure as 95% confidence interval (CI).Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline in Life Satisfaction (LISAT) Using HIV/AIDs-targeted Quality of Life (HATQoL) Questionnaire

Time: Baseline (Day 1) and at Weeks 24 and 48

Description: The HATQoL questionnaire was used to assess the health related QoL (HRQoL). It comprises of three dimensions: LISAT, medication worries (MEDWO) and disclosure worries (DISWO). The total imputed value score for MEDWO is calculated on a 0-100 scale using the formula: MEDWO 100=[100 divided by (20 minus 5)]*(MEDWO minus 5). A response of 1 in MEDWO score shows less medication worries all of the time and 5 as none of the time. The higher the score, the greater satisfaction to life and the less worry. The transformed dimension score for each domain was summarized and analyzed. LOCF was used as primary method of analysis. Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline in HIV Medication, MEDWO Using HATQoL

Time: Baseline and at Weeks 24 and 48

Description: The HATQoL questionnaire was used to assess the health related QoL (HRQoL). It comprises of three dimensions: LISAT, medication worries (MEDWO) and disclosure worries (DISWO). The total imputed value score for DISWO is calculated on a 0-100 scale using the formula: DISWO 100=[100 divided by (20 minus 5)]*(DISWO minus 5). A response of 1 in DISWO score shows less medication worries all of the time and 5 as none of the time. The higher the score, the greater satisfaction to life and the less worry. The transformed dimension score for each domain was summarized and analyzed. LOCF was used as primary method of analysis. Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline in DISWO Using HATQoL

Time: Baseline and at Weeks 24 and 48

Description: The SF-12 questionnaire consists of 7 questions which measures the degree of general health status and mental health distress. Each question is scored 0-5, except for question 2 scored 0-3. The HRQoL using SF-12 for the total score, physical component summary (PCS) and the mental component summary (MCS) were assessed for the two treatment groups. Missing Total or the component scores was imputed using LOCF. The PCS/MCS are calculated using computer software purchased from QualityMetric (http://www.qualitymetric.com). The higher the score, the better will be the health status. Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline in Health Status Using 12-item Short Form Survey (SF-12)

Time: Baseline and at Weeks 24 and 48

Description: The HIVTSQ for total treatment satisfaction score is computed with 1-11 items. These 1-11 items are summed to produce a score with a possible range of -33 to 33. The item 12 in the scale will be calculated as an individual score.The higher the score, the greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment.A score of 0 represents no change. A maximum of 5 items can be missing, the missing scores will be imputed with the mean of the completed item scores. If 6 or more items are missing, then the overall treatment satisfaction scale score should not be computed and will remain missing.LOCF was used as primary method of analysis. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. Data has been presented with respect to actual treatment received to the participants

Measure: Change From Baseline in Total Treatment Satisfaction Using HIV Treatment Satisfaction Questionnaire (HIVTSQs) at Weeks 4b, 24 and 44

Time: Baseline and at Weeks 4b, 24 and 44

Description: The HIVTSQ for total treatment satisfaction score is computed with 1-11 items. These 1-11 items are summed to produce a score with a possible range of -33 to 33. The item 12 in the scale will be calculated as an individual score.The higher the score, the greater the improvement in satisfaction with treatment; the lower the score, the greater the deterioration in satisfaction with treatment.A score of 0 represents no change. A maximum of 5 items can be missing, the missing scores will be imputed with the mean of the completed item scores. If 6 or more items are missing, then the overall treatment satisfaction scale score should not be computed and will remain missing.LOCF was used as primary method of analysis. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. Data has been presented with respect to actual treatment received to the participants

Measure: Change in Treatment Satisfaction Over Time Using HIVTSQ Change (HIVTSQc) at Week 48 in Q4W Arm

Time: Week 48

Description: The ACCEPT questionnaire is a generic medication acceptance measure assessing how participants weigh advantages and disadvantages of long-term medication.The questionnaire consists of 25 items that capture six dimensions.3 questions that focus on general acceptance of study medication will be analyzed.Items on the scale are rated as 1-5 scores:1:totally disagree,2:somewhat disagree,3:somewhat agree, 4:totally agree and 5:I don't know.Total score of the dimension is calculated as the mean of the recoded items of the dimension and then linearly transformed to be on a scale from 0 to 100:score:Total Score=(mean of the recoded items in the dimension minus1)divided by2*100.LOCF was used as primary method of analysis.Measure type was considered as mean for adjusted mean and dispersion measure as 95% CI.Baseline value is defined as the latest pre-treatment assessment with a non-missing value.Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value

Measure: Change From Baseline in Treatment Acceptance at Weeks 8, 24 and 48 Using "General Acceptance" Dimension of the Chronic Treatment Acceptance (ACCEPT) Questionnaire

Time: Baseline and at Weeks 8, 24 and 48

Description: The NRS questionnaire is used to assess the tolerability of injections in CAB LA+RPV LA arm only. The questionnaire consists of one single question and will assess maximum level of pain experienced with the most recent injections ranking from no pain (0) to extreme pain (10). Missing scores was imputed using LOCF.

Measure: Change From 4b in Tolerability of Injection at Week 5, 40 and 41 Using Numeric Rating Scale (NRS) Within CAB LA+RPV LA Arm

Time: Weeks 4b, 5, 40 and 41

Description: HIVTSQc is a 12 item questionnaire. The individual treatment change item scores on HIVTSQc scale are rated as +3 ('much more satisfied', 'much more convenient', 'much more flexible',etc.) to -3 ('much less satisfied', 'much less convenient', 'much less flexible', etc.). The higher the score, the greater the improvement in satisfaction with each aspect of treatment and the lower the score, the greater the deterioration in satisfaction with each aspect of treatment. LOCF was used as primary method of analysis. Baseline value is defined as the latest pre-treatment assessment with a non-missing value. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value.

Measure: Change From Baseline in Individual Item Scores of HIVTSQc at Weeks 4b, 24 and 44

Time: Baseline and Weeks 4b, 24 and 44

Description: Blood samples were planned to be collected at indicated time points for PK analysis of CAB LA and RPV LA. Demographic parameters including, but not limited to, age, sex, race, body weight, body mass index, and relevant laboratory parameters were planned to be evaluated as potential predictors of inter subject variability for pharmacokinetic parameters.

Measure: Number of Participants With Different Demographic Parameters for Inter-subject Variability

Time: Upto Week 48

18 A Phase IIIb, Randomized, Multicenter, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Long-acting Cabotegravir Plus Long-acting Rilpivirine Administered Every 8 Weeks or Every 4 Weeks in HIV-1-infected Adults Who Are Virologically Suppressed

This Antiretroviral Therapy as Long Acting Suppression every 2 Months (ATLAS-2M) study is designed to demonstrate the non-inferior antiviral activity and safety of CAB LA + RPV LA administered every 8 weeks (Q8W) compared to CAB LA + RPV LA administered every 4 weeks (Q4W) over a 48-week treatment period in approximately 1020 adult HIV-1 infected subjects. Subjects will be divided in 2 groups; Group 1 will include subjects receiving current anti-retroviral (ART) standard of care (SOC) therapy whereas group 2 will include subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in both groups will be randomized to receive CAB LA + RPV LA Q4W or Q8W. The study will be carried out in 3 phases including screening phase, maintenance phase and extension phase. Subjects choosing not to enter the Extension phase can complete their study participation at the Week 100 visit and enter into the 52-week Long-Term Follow-Up (LTFU) Phase as required.

NCT03299049 HIV Infections Drug: Cabotegravir Tablets Drug: Rilpivirine Tablets Drug: Cabotegravir Injectable Suspension Drug: Rilpivirine Injectable Suspension
MeSH: HIV Infections

- Any evidence of primary resistance based on the presence of any major known Integrase inhibitor (INI) or Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutation, except for K103N by any historical resistance test result. --- K103N ---

Primary Outcomes

Description: Virologic outcome for each subject will be calculated according to the food and drug administration's (FDA) Snapshot algorithm. As defined by the Snapshot algorithm, HIV-RNA >=50 copies/mL is determined by the last available HIV-1 RNA measurement while the subject is on treatment within the analysis visit window of interest.

Measure: Percentage of subjects with plasma HIV ribonucleic acid (RNA) >=50 copies per milliliter (copies/mL) at Week 48

Time: Week 48

Secondary Outcomes

Description: The antiviral and immunologic activity of CAB LA + RPV LA Q8W will be compared to CAB LA + RPV LA Q4W at Week 24, Week 48 and Week 96 using the FDA Snapshot algorithm. Subjects with last available HIV-1 RNA measurement <50 copies/mL while the subject is on treatment within the analysis visit window of interest are classified as responders; subjects without evaluable HIV-RNA data for the visit of interest or who change treatment not permitted per protocol before the analysis window are considered non-responders.

Measure: Percentage of subjects with plasma HIV-1 RNA <50 copies/mL

Time: Up to Week 96

Description: CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 copies/mL after prior suppression to <200 copies/mL. CVF will be analyzed through Week 24, Week 48 and Week 96 as a measure of antiviral and immunologic activity of CAB LA and RPV LA.

Measure: Percentage of subjects with protocol-defined confirmed virologic failure (CVF)

Time: Up to Week 96

Description: Virologic outcome for each subject will be calculated according to the FDA Snapshot algorithm. As defined by the Snapshot algorithm, HIV-RNA >=50 copies/mL is determined by the last available HIV-1 RNA measurement while the subject is on treatment within the analysis visit window of interest.

Measure: Percentage of subjects with HIV-RNA >=50 copies/mL

Time: Up to Week 96

Description: Change from Baseline in viral load will be assessed over time including Week 48 and Week 96.

Measure: Change from Baseline in viral load

Time: Baseline and Up to Week 96

Description: Lymphocyte subsets will be collected for assessment by flow cytometry at specific time points including Week 48 and Week 96.

Measure: Change from Baseline in cluster of differentiation (CD)4+ cell counts

Time: Baseline and Up to Week 96

Description: An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.

Measure: Number of subjects with Adverse events (AEs) and serious AEs

Time: Up to Week 96

Description: Clinical chemistry parameters including blood urea nitrogen (BUN), creatinine, glucose, sodium, potassium, chloride, total carbon-di-oxide (CO2), lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, phosphate, total bilirubin, albumin, creatine phosphokinase and lipid panel will be analyzed as a measure of safety.

Measure: Number of subjects with abnormal clinical chemistry values

Time: Up to Week 96

Description: Clinical hematology parameters including platelet count, red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscle volume (MCV), neutrophils, lymphocytes, monocytes, eosinophils and basophils will be analyzed as a measure of safety.

Measure: Number of subjects with abnormal clinical hematology values

Time: Up to Week 96

Description: Subjects who discontinue treatment due to AEs will be analyzed as a measure of safety.

Measure: Percentage of subjects who discontinue treatment due to AEs

Time: Up to Week 96

Description: Change from Baseline in albumin will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in albumin

Time: Baseline and up to Week 96

Description: Change from Baseline in Alkaline phosphatase, ALT, AST, creatine phosphokinase, lipase will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in Alkaline phosphatase, ALT, AST, creatine phosphokinase, lipase

Time: Baseline and up to Week 96

Description: Change from Baseline in total bilirubin and creatinine will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in total bilirubin and creatinine

Time: Baseline and up to Week 96

Description: Change from Baseline in glucose, sodium, potassium, total CO2, BUN, chloride, phosphate will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in glucose, sodium, potassium, total CO2, BUN, chloride, phosphate

Time: Baseline and up to Week 96

Description: Change from Baseline in total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in total cholesterol, High density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides

Time: Baseline and Up to Week 96

Description: Change from Baseline in creatinine clearance will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in creatinine clearance

Time: Baseline and Up to Week 96

Description: Change from Baseline in basophils, eosinophils, monocytes, lymphocytes, neutrophils and platelet count will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in basophils, eosinophils, monocytes, lymphocytes, neutrophils and platelet count

Time: Baseline and Up to Week 96

Description: Change from Baseline in hematocrit levels will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in hematocrit levels

Time: Baseline and Up to Week 96

Description: Change from Baseline in hemoglobin levels will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in hemoglobin levels

Time: Baseline and Up to Week 96

Description: Change from Baseline in RBC count will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in RBC count

Time: Baseline and Up to Week 96

Description: Change from Baseline in WBC count will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in WBC count

Time: Baseline and Up to Week 96

Description: Change from Baseline in MCV levels will be assessed up to long-term follow-up visits as a measure of safety.

Measure: Change from Baseline in MCV levels

Time: Baseline and Up to Week 96

Description: Whole venous blood samples will be obtained from each subject for analysis of potential genotypic resistance to CAB, RPV.

Measure: Number of incidences of treatment emergent genotypic resistance

Time: Up to Week 96

Description: Whole venous blood samples will be obtained from each subject for analysis of potential phenotypic resistance to CAB, RPV.

Measure: Number of incidences of treatment emergent phenotypic resistance

Time: Up to Week 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: Trough plasma concentration (Ctrough) of CAB LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: Ctrough of RPV LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: Ctrough of CAB LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: Ctrough of RPV LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: Maximum plasma concentration (Cmax) of CAB LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: Cmax of RPV LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: Cmax of CAB LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: Cmax of RPV LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: Area under the curve (AUC) of CAB LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: AUC of RPV LA: Q4W dosing

Time: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.

Measure: AUC of CAB LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.

Measure: AUC of RPV LA: Q8W dosing

Time: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96

Description: Demographic parameters including, but not limited to, age, sex, race, body weight, body mass index, and relevant laboratory parameters will be evaluated as potential predictors of inter participant variability for pharmacokinetic parameters.

Measure: Number of subjects with different demographic parameters: For inter-participant variability

Time: Up to Week 96

Description: Demographic parameters including, but not limited to, age, sex, race, body weight, body mass index, and relevant laboratory parameters will be evaluated as potential predictors of inter participant variability for pharmacokinetic parameters.

Measure: Number of subjects with different demographic parameters: For intra participant variability

Time: Up to Week 96

Description: The HAT-QoL is a 42-item questionnaire grouped into nine dimensions, assessing overall function and well-being. A shorter version of this original HAT-QoL will be used in the present study which will contain 14-items grouped into the three following dimensions: "life satisfaction", "disclosure worries" and "HIV medication". All items use a ''past 4 weeks'' timeframe and a Likert response scale from 1=''all of the time'' to 5=''none of the time''.

Measure: Change from Baseline in health related quality of life (HRQoL) of subjects using the HIV/Acquired immunodeficiency syndrome (AIDS) Targeted Quality of Life (HAT-QoL) questionnaire

Time: Baseline and up to Week 48

Description: HIVTSQ is a 10-item questionnaire which is used specifically to measure satisfaction with medication for people infected with HIV.

Measure: Change from Baseline in total "treatment satisfaction" score of the HIV Treatment Satisfaction Status Questionnaire (HIVTSQs)

Time: Baseline and up to Week 48

Description: HIVTSQ is a 10-item questionnaire which is used specifically to measure satisfaction with medication for people infected with HIV.

Measure: Change from Baseline in individual item score of HIVTSQs

Time: Baseline and Up to Week 48

Description: HIVTSQc is the change version of original HIVTSQs. HIVTSQc enhances the sensitivity by allowing those who were satisfied at Baseline to express even greater satisfaction at follow-up.

Measure: Change in treatment satisfaction using the HIV Treatment Satisfaction Change Questionnaire (HIVTSQc)

Time: Week 48

Description: Change from Week 8 in dimension score which assess Bother of Injection Site Reactions (ISRs), Leg movement, Sleep, and Injection Acceptance will be evaluated using PIN questionnaire. This measure contains 21 items and scores range from 1 to 5 where 1= the most favorable perception of vaccination while 5= the most unfavorable.

Measure: Change from Week 8 in Dimension scores using the Perception of injection questionnaire (PIN)

Time: Week 8 and up to Week 48

Description: Change from Week 8 in individual item scores which assess pain during injection, anxiety before and after injection, willingness to be injected in the future and overall satisfaction with mode of administration over time will be evaluated using the PIN questionnaire. This measure contains 21 items and scores range from 1 to 5 where 1= the most favorable perception of vaccination while 5= the most unfavorable.

Measure: Change from Week 8 in individual item score using PIN

Time: Week 8 and Up to Week 48

Description: The ACCEPT questionnaire, a 25 item questionnaire, is a generic medication acceptance measure assessing how patients weigh advantages and disadvantages of long-term medications. The study will use three questions that focus on general acceptance of study medication.

Measure: Change from Baseline in treatment acceptance using the "General acceptance" dimension of the Chronic Treatment Acceptance (ACCEPT) questionnaire

Time: Baseline and up to Week 48

Description: Lymphocyte subsets will be collected for assessment by flow cytometry at specific time points including Week 48 and Week 96.

Measure: CD4+ cell counts

Time: Baseline and up to Week 96

Description: The preference questionnaire will include 3 questions evaluating preference of HIV treatment and the attributes supporting this preference. It will assess will assess whether subjects prefer the CAB LA + RPV LA injectable treatment.

Measure: Number of subjects preferring CAB LA+ RPV LA injectable treatment, using preference questionnaire

Time: Week 48

Description: The preference questionnaire will include 3 questions evaluating preference of HIV treatment and the attributes supporting this preference. It will assess will assess whether subjects prefer the CAB LA + RPV LA Q8W injectable treatment.

Measure: Number of subjects preferring CAB LA + RPV LA Q8W, using preference questionnaire

Time: Week 48

19 A Qualitative Hybrid III Implementation Study to Identify and Evaluate Strategies for Successful Implementation of the Cabotegravir + Rilpivirine Long-acting Injectable Regimen in the US

Chronic human immunodeficiency virus (HIV) infection in adults continues to be characterized by increased development of resistant virus, increased transmission of resistant virus and issues associated with the long-term toxicity of anti-retroviral therapy (ART), despite advances in development of new ART, which provides extensive insight in management of HIV-infected individuals. Cabotegravir (CAB) is a potent integrase inhibitor (INI) and rilpivirine (RPV) is a potent non-nucleoside reverse transcriptase inhibitor (NNRTI). A two-drug regimen (DR)with CAB plus RPV long acting (LA) product offers many potential advantages over daily oral regimens including better tolerability, improved compliance, adherence, less likely to develop resistance, and overall treatment satisfaction in virologically suppressed subjects. This is a single-arm, open-label, multicenter, short term facilitation study to evaluate the effect of an implementation strategy on the degree of acceptability, appropriateness, feasibility, fidelity and sustainability of clinical practices to deliver the CAB+RPV LA regimen to HIV infected subjects and to also measure subject satisfaction by recording timeliness of visits, length of visit and their education. Approximately 135 subjects will be enrolled in the study and the total duration of the study will be approximately 52-weeks.

NCT04001803 HIV Infections Drug: CAB LA+RPV LA
MeSH: HIV Infections

- Any evidence of primary resistance based on the presence of any major known INI or NNRTI resistance-associated mutation, except for K103N, (International acquired immune deficiency syndrome [AIDS] Society [IAS]-USA) by any historical resistance test result. --- K103N ---

Primary Outcomes

Description: The responses for acceptability will be measured on a Likert scale ranging from 0 to 5 with higher values representing better outcomes.

Measure: Change from Baseline in the acceptability of intervention measure (AIM) questionnaire in staff study subjects based on Likert scale

Time: Baseline and 4 months

Description: The responses for acceptability will be measured on a Likert scale ranging from 0 to 5 with higher values representing better outcomes.

Measure: Change from Baseline for AIM in staff study subjects

Time: Baseline and 12 months

Description: The responses for acceptability will be measured on a Likert scale ranging from 0 to 5 with higher values representing better outcomes.

Measure: Change from Baseline for AIM in subjects with HIV infection at 4 months

Time: Baseline and 4 months

Description: The responses for acceptability will be measured on a Likert scale ranging from 0 to 5 with higher values representing better outcomes.

Measure: Change from Baseline for AIM in subjects with HIV infection

Time: Baseline and 12 months

Description: The responses for appropriateness will be measured on a Likert scale ranging from 0 to 5 with higher values representing better outcomes.

Measure: Change from Baseline for intervention appropriateness measure (IAM) in staff study subjects at 4 months

Time: Baseline and 4 months

Description: The responses for appropriateness will be measured on a Likert scale ranging from 0 to 5 with higher values representing better outcomes.

Measure: Change from Baseline for IAM in staff study subjects

Time: Baseline and 12 months

Description: The responses for appropriateness will be measured on a Likert scale ranging from 0 to 5 with higher values representing better outcomes.

Measure: Change from Baseline for IAM in subjects with HIV infection

Time: Baseline and 12 months

Description: The responses for appropriateness will be measured on a Likert scale ranging from 0 to 5 with higher values representing better outcomes.

Measure: Change from Baseline for IAM in subjects with HIV infection at 4 months

Time: Baseline and 4 months

Description: The responses for appropriateness will be measured on a Likert scale ranging from 0 to 5 with higher values representing better outcomes.

Measure: Change from Baseline for feasibility of intervention measure (FIM) in staff study subjects at 4 months

Time: Baseline and 4 months

Description: The responses for feasibility will be measured on a Likert scale ranging from 0 to 5 with higher values representing better outcomes.

Measure: Change from Baseline for FIM in staff study subjects

Time: Baseline and 12 months

Secondary Outcomes

Description: The organizational facilitators and barriers are assessed using consolidated framework for implementation research (CFIR). CFIR comprises of 39 constructs organized into 5 domains.

Measure: Change from Baseline for facilitators using semi-structure interview (SSI) in staff study subjects at 4 months

Time: Baseline and 4 months

Description: The organizational facilitators and barriers are assessed using consolidated framework for implementation research (CFIR). CFIR comprises of 39 constructs organized into 5 domains.

Measure: Change from Baseline for facilitators using SSI in staff study subjects

Time: Baseline and 12 months

Description: The organizational facilitators and barriers are assessed using CFIR. CFIR comprises of 39 constructs organized into 5 domains.

Measure: Change from Baseline for barriers using SSI in staff study subjects at 4 months

Time: Baseline and 4 months

Description: The organizational facilitators and barriers are assessed using CFIR. CFIR comprises of 39 constructs organized into 5 domains.

Measure: Change from Baseline for barriers using SSI in staff study subjects

Time: Baseline and 12 months

Description: The organizational facilitators and barriers are assessed using CFIR. CFIR comprises of 39 constructs organized into 5 domains.

Measure: Change from Baseline for facilitators using SSI in subjects with HIV infection

Time: Baseline and 12 months

Description: The organizational facilitators and barriers are assessed using CFIR. CFIR comprises of 39 constructs organized into 5 domains.

Measure: Change from Baseline for barriers using SSI in subjects with HIV infection

Time: Baseline and 12 months

Description: The barriers will be assessed by short-term facilitation like coaching calls which will include combination of structured and open-ended questions.

Measure: Number of barriers assessed among clinics using short-term facilitation

Time: Up to 6 months

Description: The facilitators will be assessed by short-term facilitation like coaching calls which will include combination of structured and open-ended questions.

Measure: Number of facilitators assessed among clinics using short-term facilitation

Time: Up to 6 months

Description: The best practice sharing among clinics will be assessed by short-term facilitation like coaching calls which will include combination of structured and open-ended questions.

Measure: Number of best practices sharing assessed among clinics using short-term facilitation

Time: Up to 6 months

Description: The use of support materials/toolkit will be assessed using survey responses to a series of questions.

Measure: Change from Baseline for the use of support materials/tool kit of staff study subjects at 4 months

Time: Baseline and 4 months

Description: The use of support materials/toolkit will be assessed using survey responses to a series of questions.

Measure: Change from Baseline for the use of support materials/tool kit of staff study subjects

Time: Baseline and 12 months

Description: The use of support materials/toolkit will be assessed using survey responses to a series of questions.

Measure: Change from Baseline for the use of support materials/toolkit of subjects with HIV infection at 4 months

Time: Baseline and 4 months

Description: The use of support materials/toolkit will be assessed using survey responses to a series of questions.

Measure: Change from Baseline for the use of support materials/toolkit of subjects with HIV infection

Time: Baseline and 12 months

Description: The use of support materials/toolkit will be assessed through SSI.

Measure: Number of support materials/toolkit used by staff study subjects

Time: Up to 12 months

Description: The implementation of fidelity will be assessed using SSI from the validated CFIR framework.

Measure: Number of subjects receiving injections within target window at 4 months

Time: Baseline and 4 months

Description: The implementation of fidelity will be assessed using SSI from the validated CFIR framework.

Measure: Number of subjects receiving injections within target window

Time: Up to 12 months

Description: The implementation sustainability in staff study subjects will be assessed using PSAT tool. This tool evaluates the capability of clinics to maintain processes developed to administer CAB+RPV injection in routine clinical settings after conclusion of the study.

Measure: Implementation sustainability assessed in staff study subjects using program sustainability assessment tool (PSAT)

Time: At month 12

Description: Subject survey responses will be assessed to measure subject satisfaction by calculating timelines of visit, length of visit and subject education.

Measure: Number of survey responses with subject satisfaction at month 1

Time: At month 1

Description: Subject survey responses will be assessed to measure subject satisfaction by calculating timelines of visit, length of visit and subject education.

Measure: Number of survey responses with subject satisfaction at month 4

Time: At month 4

Description: Subject survey responses will be assessed to measure subject satisfaction by calculating timelines of visit, length of visit and subject education.

Measure: Number of survey responses with subject satisfaction at month 12

Time: At months 12

Description: The timeliness of visit for each subject will be assessed using SSI responses.

Measure: Change from Baseline in subject's timeliness of visit

Time: Baseline and at month 12

Description: The length of hospital visit for each subject will be assessed using SSI responses

Measure: Change from Baseline in subject's length of visit

Time: Baseline and at month 12

Description: The subject's knowledge about CAB + RPV LA treatment will be assessed using SSI responses

Measure: Change from Baseline in subject's knowledge about the CAB + RPV LA treatment

Time: Baseline and at month 12

Description: The length of subject visit will be assessed from arrival until departure from clinic.

Measure: Length of subject visit

Time: At month 1

Description: The length of subject visit will be assessed from arrival until departure from clinic.

Measure: Length of subject visit

Time: At month 5

Description: The length of subject visit will be assessed from arrival until departure from clinic.

Measure: Length of subject visit

Time: At month 11

Description: Plasma samples will be collected from the subject at specific time points. The Abbott RealTime HIV-1 Assay lower limit of detection (LLOD) 40 c/mL, will be used.

Measure: Number of subjects with plasma HIV-1 Ribo Nucleic Acid (RNA)<50 copies/milliliter (c/mL)

Time: Up to 12 months

Description: CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 c/mL after prior suppression to <200 c/mL.

Measure: Number of subjects with confirmed virologic failure (CVF)

Time: Up to 12 months

Description: Blood samples will be collected and used for the analysis of genotypic resistance in subjects with CVF.

Measure: Number of subjects with treatment emergent genotypic resistance to CAB and RPV

Time: Up to 12 months

Description: Blood samples will be collected and used for the analysis of phenotypic resistance in subjects with CVF.

Measure: Number of subjects with phenotypic resistance to CAB and RPV

Time: Up to 12 months

Description: An AE is any untoward medical occurrence in a subject or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect and other situations which involve medical or scientific judgment, and is associated with liver injury and impaired liver function.

Measure: Number of subjects with adverse events (AEs) and serious adverse events (SAEs)

Time: Up to 12 months

Description: An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of subjects who will discontinue the treatment due to AEs will be reported.

Measure: Number of subjects who discontinue treatment due to AEs over time

Time: Up to 12 months

Description: Blood samples will be collected to measure platelets, red blood cells (RBC) count, white blood cells (WBC) count (absolute), hemoglobin, hematocrit, mean corpuscular volume (MCV), neutrophils, lymphocytes, monocytes, eosinophils and basophils.

Measure: Number of subjects with abnormal hematology findings

Time: Up to 12 months

Description: Blood samples will be collected to measure blood urea nitrogen (BUN), creatinine, glucose, sodium, potassium, chloride, Total carbon dioxide (CO2), lipase, phosphate, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, albumin, creatine phosphokinase (CK) and creatinine clearance.

Measure: Number of subjects with abnormal clinical chemistry findings

Time: Up to 12 months

Description: Urine samples will be collected and analyzed from subjects at indicated time points.

Measure: Number of subjects with abnormal urinalysis

Time: Up to 12 months

Description: The ISRs will be assessed through-out the study. All ISRs that are either serious, grade 3 or higher or persisting beyond 2 weeks will be discussed with the Medical Monitor to determine etiology and assess appropriate continued study participation.

Measure: Number of subjects with injection site reactions (ISRs) over time

Time: Up to 12 months

Description: Blood samples will be collected to measure hematology parameters including: platelet count, WBC count, basophil count, eosinophil count, lymphocyte count , monocyte count and neutrophil count.

Measure: Change from Baseline in hematology parameters of platelet count, WBC count, basophil count, eosinophil count, lymphocyte count , monocyte count and neutrophil count (all 10^9 cells/Liter)

Time: Baseline and Up to 12 months

Description: Blood samples will be collected to measure RBC count.

Measure: Change from Baseline in hematology parameters-RBC count

Time: Baseline and Up to 12 months

Description: Blood samples will be collected to measure Hemoglobin.

Measure: Change from Baseline in hematology parameters- Hemoglobin

Time: Baseline and Up to 12 months

Description: Blood samples will be collected to measure hematocrit.

Measure: Change from Baseline in hematology parameter-hematocrit

Time: Baseline and Up to 12 months

Description: Blood samples will be collected to measure MCV.

Measure: Change from Baseline in hematology parameter-MCV

Time: Baseline and Up to 12 months

Description: Blood samples will be collected to measure sodium, potassium, carbon-dioxide, chloride, and glucose.

Measure: Change from Baseline in clinical laboratory parameters of sodium, potassium, carbon-dioxide, chloride and glucose (all millimoles per liter)

Time: Baseline and Up to 12 months

Description: Blood samples will be collected to measure creatinine and total bilirubin

Measure: Change from Baseline in clinical laboratory parameters of creatinine and total bilirubin

Time: Baseline and Up to 12 months

Description: Blood samples will be collected to measure ALT, ALP and AST.

Measure: Change from Baseline in clinical laboratory parameters of ALT, ALP and AST

Time: Baseline and Up to 12 months

Description: Blood samples will be collected to measure Creatine phosphokinase.

Measure: Change from Baseline in clinical laboratory parameter-Creatine phosphokinase

Time: Baseline and Up to 12 months

Description: Blood samples will be collected to measure Creatinine clearance

Measure: Change from Baseline in clinical laboratory parameter-Creatinine clearance

Time: Baseline and Up to 12 months

Description: Blood samples will be collected to measure lipase.

Measure: Change from Baseline in clinical laboratory parameter-lipase

Time: Baseline and Up to 12 months

Description: Blood samples will be collected to measure BUN.

Measure: Change from Baseline in clinical laboratory parameters-BUN

Time: Baseline and Up to 12 months

Description: Urine samples will be collected at the specified timepoints, for assessment of urine albumin to creatinine ratio.

Measure: Change from Baseline in urinalysis parameters, urine albumin to creatinine ratio

Time: Baseline and Up to 12 months

Description: Urine samples will be collected at the specified timepoints, for assessment of urine protein to creatinine ratio.

Measure: Change from Baseline in urinalysis parameters, urine protein to creatinine ratio

Time: Baseline and Up to 12 months

Description: Urine samples will be collected at the specified timepoints, for assessment of urine phosphate.

Measure: Change from Baseline in urinalysis parameters, urine phosphate

Time: Baseline and Up to 12 months


HPO Nodes