SNPMiner Trials by Shray Alag


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Report for Mutation Q148H

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 5 clinical trials

Clinical Trials


1 A Pilot Study of Highly Active Antiretroviral Therapy Using Isentress (Raltegravir) and Epzicom (Abacavir/Lamivudine) in Antiretroviral Naive HIV-Infected Subjects

To evaluate the efficacy and safety of Raltegravir and Epzicom over 48 weeks in ART-naive HIV-infected subjects.

NCT00740064 HIV Infections Drug: Raltegravir and Abacavir/Lamivudine
MeSH: HIV Infections

Exclusion Criteria: - Screening HIV-1 genotype indicating the presence of any of the following mutations: K65R, L74V, and Y115F 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 ABC and 3TC resistance, and mutations Q148H/R/K and N155H associated with RTG resistance. --- K65R --- --- L74V --- --- Y115F --- --- M41L --- --- D67N --- --- K70R --- --- K219Q --- --- Q148H ---

Primary Outcomes

Measure: To evaluate the efficacy and safety of RTG and ABC/3TC over 48 weeks in ART-naive HIV-infected subjects.

Time: 48 weeks

Secondary Outcomes

Measure: To assess the immunologic response, changes in fasting lipids, renal function, and development of resistance of the study regimen

Time: 48 weeks

2 A Pilot Efficacy and Safety Trial of Raltegravir Plus Darunavir/Ritonavir for Treatment-Naive HIV-1-Infected Subjects

The purpose of this study is to assess the effectiveness and safety of an antiretroviral therapy (ART) regimen consisting of raltegravir (RAL) and darunavir (DRV)/ritonavir (RTV) as first-line therapy in treatment-naïve participants.

NCT00830804 HIV-1 Infections Drug: Raltegravir Drug: Darunavir/Ritonavir

- Screening HIV genotype obtained any time prior to study entry with more than one DRV resistance-associated mutation [RAM] (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, I84V, and L89V) or L76V alone - Known major integrase inhibitor RAM(s), including N155H, Q148H/R/K, Y143C/R, and G140S - Severe renal insufficiency requiring hemodialysis or peritoneal dialysis - Treatment with immunomodulators within 30 days prior to study entry. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- I54M --- --- T74P --- --- I84V --- --- L89V --- --- L76V --- --- N155H --- --- Q148H ---

Primary Outcomes

Description: Virologic failure is defined as: at week 12, confirmed plasma HIV-1 RNA >= 1000 copies/ml or confirmed rebound from the week 4 value by >0.5 log10 copies/ml (for subjects with week 4 value <= 50 copies/ml, confirmed rebound to >50 copies/ml); at week 24 or later, confirmed value > 50 copies/ml. Viral load confirmation was scheduled 7-35 days after initial virologic failure. The proportion was estimated using Kaplan-Meier method. An adaptation of Greenwood's variance estimate was used in constructing the confidence interval.

Measure: Proportion of Participants With Virologic Failure After Initiating RAL Plus DRV/RTV at or Prior to Week 24

Time: From start of study treatment to week 24

Secondary Outcomes

Description: The proportion of participants with virologic failure (see primary outcome measure for definition) and/or premature treatment discontinuation/modification and/or death was estimated using Kaplan-Meier method. An adaptation of Greenwood's variance estimate was used in constructing the confidence interval.

Measure: Proportion of Participants With Virologic Failure or Off Study Treatment Regimen or Death at or Prior to Week 24

Time: From start of study treatment to Week 24

Description: Results report the week 1 change from baseline (week 1 - baseline) in HIV-1 RNA. Baseline HIV-1 RNA was computed as the mean of the log10 HIV-1 RNA values at pre-entry and study entry.

Measure: Change in Plasma HIV-1 RNA From Baseline to Week 1

Time: Baseline and week 1

Description: Results report the percentage of participants with plasma HIV-1 RNA < 50 copies/ml or <200 copies/ml at week 24.

Measure: Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/ml or <200 Copies/ml at Week 24

Time: From start of study treatment to week 24

Description: Results report the percentage of participants with plasma HIV-1 RNA <50 copies/ml or <200 copies/ml at week 48.

Measure: Proportion of Participants With Plasma HIV-1 RNA <50 Copies/ml or <200 Copies/ml at Week 48

Time: From start of study treatment to week 48

Description: Signs, symptoms and laboratory values were graded according to the Division of AIDS Adverse Event Grading System. Results report the percentage of participants who had grade 3 or higher events, or events of any grade which led to a permanent change or discontinuation of study treatment, which occurred any time from start of treatment to end of treatment.

Measure: Proportion of Participants Who Experienced Signs/Symptoms or Laboratory Toxicities Grade 3 or Higher, or of Any Grade Which Led to a Permanent Change or Discontinuation of Study Treatment

Time: From start of study treatment to week 52

Description: Results report the number of participants who had resistance to non-nucleoside reverse transciptase inhibitors (NNRTI), nucleoside reverse transciptase inhibitors (NRTI) and protease inbitors (PI) based on genotypic resistance testing done prior to participant's entry into the study. Participants are classified into one (and only one category) based on the maximum number of drug class resistance seen for the participant.

Measure: Number of Participants With Pretreatment Drug Resistance

Time: At screening

Description: Results report the number of participants who had integrase resistance mutation(s) detected at the time of virologic failure.

Measure: Number of Participants With Integrase Drug Resistance at Virologic Failure

Time: From 12 weeks after starting study treatment to week 52

Description: Results report the number of participants who had protease resistance mutation(s) detected at the time of virologic failure.

Measure: Number of Participants With Protease Drug Resistance at Virologic Failure

Time: From 12 weeks after starting study treatment to week 52

Description: At each study visit, adherence was measured in terms of the number of missed doses each participant had over a 4-day recall for each drug. Adherence for all study visit weeks were combined for an overall measure of adherence. Participants who had zero missed doses on all weeks in all drugs while on study were classified as having an overall "perfect" adherence.

Measure: Number of Participants With Perfect Overall Adherence by Self Report

Time: From one week after starting study treatment to week 52

Description: Results report the week 24 change from week 0 (week 24 - week 0) fasting total cholesterol, high-density lipoprotein and triglyceride.

Measure: Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 24

Time: From start of study treatment through week 24

Description: Results report the week 24 change from week 0 (week 24 - week 0) fasting low-density lipoprotein (LDL). For participants whose calculated fasting LDL and direct fasting LDL were both reported, only the calculated fasting LDL was used. Direct fasting LDL was reported when the participant had high fasting triglyceride.

Measure: Change in Fasting Low-density Lipoprotein at Week 24

Time: From start of study treatment through week 24

Description: Results report the week 48 change from week 0 (week 48 - week 0) fasting total cholesterol, high-density lipoprotein and triglyceride.

Measure: Changes in Fasting Total Cholesterol, High-density Lipoprotein and Triglyceride at Week 48

Time: From start of study treatment through week 48

Description: Results report the week 48 change from week 0 (week 48 - week 0) fasting low-density lipoprotein (LDL). For participants whose calculated fasting LDL and direct fasting LDL were both reported, only the calculated fasting LDL was used. Direct fasting LDL was reported when the participant had high fasting triglyceride.

Measure: Change in Fasting Low-density Lipoprotein at Week 48

Time: From start of study treatment through week 48

Description: Results report the week 48 change from baseline (week 48 - baseline) in CD4 count. Baseline CD4 count was computed as the mean of CD4 count values at pre-entry and study entry.

Measure: Change in CD4 Count at Week 48

Time: From start of study treatment through week 48

Description: Plasma trough concentrations (ng/ml) of Raltegravir (RAL) below the detection limit (10 ng/ml) were replaced by half the corresponding lower limit of quantitation. Geometric mean of trough concentrations obtained within the prescribed trough time (within 9-15 hours after the last RAL dose) was computed for each participant. For participants who experienced virologic failure (see primary outcome measure definition), only those concentrations on or before virologic failure confirmation were used in the geometric mean computation.

Measure: Plasma Trough Concentration of Raltegravir

Time: From start of study treatment to week 52

Description: Plasma trough concentrations (ng/ml) of Darunavir (DRV) below the detection limit (50 ng/ml) were replaced by half the corresponding lower limit of quantitation. Geometric mean of trough concentrations obtained within the prescribed trough time (within 20-28 hours after the last DRV dose) was computed for each participant. For participants who experienced virologic failure (see primary outcome measure definition), only those concentrations on or before virologic failure confirmation were used in the geometric mean computation.

Measure: Plasma Trough Concentration of Darunavir

Time: From start of study treatment to week 52

3 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

- No mutation (either on pre-ART genotype or on DNA genotype at screening) among the following: T66K, G118R, V151L, S153F/Y, R263K, T66K + L74M, E92Q + N155H, Q148R +N155H, Q148H/K/R with at least one mutation of L74I or E138A/K/T or G140A/C/S - Negative HBs Ag - Informed consent form signed by patient and investigator - A specific consent for the pharmacokinetic substudy will be signed by the 10 patients of the pilot phase of the trial who will be randomized to the Dolutegravir + Rilpivirine arm and will volunteer for this PK study - Patient covered with health insurance - Effective contraception Exclusion Criteria: - HIV-2 infection - Dialysis or severe renal failure (creatinine clearance < 30 ml/min) - History of decompensated liver disease - History of HIV-associated neurocognitive disorders - AST or ALT > 5 x ULN - Positive HBc Ac and negative HBs Ac - Patient receiving a proton pump inhibitor that cannot be switched to another anti-secretory drug - Current pregnancy or breastfeeding - Patient involved in another research that precludes enrolment in another trial - Patient under guardianship, or deprived of liberty by a court or administrative decision. --- T66K --- --- G118R --- --- V151L --- --- S153F --- --- R263K --- --- T66K --- --- L74M --- --- E92Q --- --- N155H --- --- Q148R --- --- Q148H ---

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

4 Darunavir/Cobicistat and Dolutegravir to Maintain Virologic Suppression and Reduce NRTI-associated Toxicity (The 'deNUC' Study; TMC114HIV2030)

This is a clinical research study to see if switching to Darunavir/Cobicistat ((PREZCOBIX™, DRV/COBI ) and Dolutegrivir (Tivicay®, DTG) in HIV-infected individuals with undetectable HIV viral load on nucleos(t)ide reverse transcriptase inhibitor (NRTI)-containing therapy will be effective in maintaining virologic suppression at 48 weeks of treatment.

NCT02499978 HIV/AIDS Drug: Darunavir/Cobicistat Drug: Dolutegravir

Prohibited protease mutations: V11I, V32I, L33F, I47V/A/L, I50V, I54T/S/L/M, T74P, L76V, V82F, I84V, or L89V Prohibited INSTI mutations: E92Q, E92K/A, G140S/A/C, Q148H/R/K or Q148 substitution plus any of the following: L74I/M, E138A/D/K/T, G140A/S, Y143H/R, E157Q, G163E/K/Q/R/S, or G193E/R. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54T --- --- T74P --- --- L76V --- --- V82F --- --- I84V --- --- L89V --- --- E92Q --- --- E92K --- --- G140S --- --- Q148H ---

Primary Outcomes

Description: Compare between arms the proportion of patients maintaining virologic suppression (i.e., no confirmed HIV RNA levels ≥200 copies/mL) at Week 24

Measure: Virologic suppression (24 weeks)

Time: 24 weeks

Secondary Outcomes

Description: Evaluate the proportion of participants who maintain virologic suppression 24 weeks post-switch (i.e. at 24 weeks in the immediate switch arm and at 48 weeks in the delayed switch arm)

Measure: Virologic Suppression (48 weeks)

Time: 48 weeks

5 Efficacy and Safety of a Simplification Strategy Based on Dolutegravir and Darunavir / Cobicistat vs Optimized Treatment in Suppressed HIV-1-infected Patients Carrying Archived Multidrug Resistance Mutations.

The availability of antiretroviral therapy has led to a reduction in morbidity and mortality in patients with chronic HIV infection. The treatment, however, is not free of side effects, has potential interactions with other medications, is expensive and can be complex, especially in those patients who are very experienced and with mutations that give them resistance to multiple drugs. For this reason, the development of simplification strategies that avoid unnecessary exposure to antiretroviral agents remains of great interest. This is a simplification study, in which the investigators try to evaluate that with less medication the investigator can maintain the same virological control of the disease. This would mean a lower burden of medication for patients, facilitating its administration and reducing the number of unwanted side effects. Specifically, the investigators intend to evaluate the treatment with Darunavir / cobicistat plus Dolutegravir as a simplification strategy, since both drugs are taken once a day, have a powerful antiviral activity, even against antiretroviral resistant viruses, and are among the best tolerated (with fewer side effects). The results reported in some observational studies suggest that two-drug therapy (bitherapy) as a simplification strategy could also be safe and effective, however, as far as the investigators know, there are no data and clinical trials that specifically evaluate darunavir / cobicistat plus dolutegravir as a strategy of simplification.

NCT03683524 HIV-1 Infection Drug: Dolutegravir (DTG) plus Darunavir/cobicistat (DRV/cobi). Drug: Current ART

T66I, 74M, E92Q, T97A, F121Y, E138A/K, G140A/S, Y143R/H/C, S147G, Q148H/K/R, N155H AND R263K) in historical genotyping tests. --- T66I --- --- E92Q --- --- T97A --- --- F121Y --- --- E138A --- --- G140A --- --- Y143R --- --- S147G --- --- Q148H ---

Primary Outcomes

Description: HIV-1 RNA < 50 copies/mL using a Time to Loss of Virological Response (TLOVR).

Measure: Plasma HIV-1 RNA < 50 copies/mL at 48 weeks

Time: week 48

Secondary Outcomes

Description: Percentage of patients developing ART-associated adverse events leading to treatment discontinuation.

Measure: Percentage of patients developing ART-associated adverse events

Time: Since baseline to week 48

Description: CD4+ cell count changes

Measure: Changes in CD4+ cell count

Time: Since baseline to week 48

Description: Emergence of new mutations in HIV-1 protease and integrase assessed with a genotyping test (attempted on any post Day 1 sample with HIV-1 RNA ≥ 50 copies/mL).

Measure: Emergence of new mutations in HIV-1 protease and integrase

Time: Baseline and in case of virological failure, defined as ≥ 50 copies/mL in 2 consecutive determinations or a single HIV-1 RNA values > 1000 copies/mL. We can observe a virological failure throughout the study (from baseline to week 48)

Description: HIV-1 RNA< 50 copies/mL at 24 weeks by TLOVR

Measure: Plasma HIV-1 RNA < 50 copies/mL at 24 weeks

Time: Week 24

Description: HIV-1 RNA < 50 copies/mL at 24 and 48 weeks using the FDA snapshot analysis (sensitivity analysis).

Measure: Plasma HIV-1 RNA < 50 copies/mL at 24 and 48 weeks

Time: Week 24 and 48

Description: Description of plasmatic trough levels of DTG and DRV/cobi in the experimental group, and in those participants experiencing virological failure.

Measure: DTG and DRV/cobi plasma concentration

Time: Week 4

Description: ART prices

Measure: Cost associated with the antirretroviral treatment of the study

Time: Since baseline to week 48

Description: Prices of clinical controls during the study

Measure: Estimated costs of clinical controls

Time: Since baseline to week 48

Measure: Genotyping tests cost

Time: At virological failure, defined as ≥ 50 copies/mL in 2 consecutive determinations or a single HIV-1 RNA values > 1000 copies/mL. We can observe a virological failure throughout the study (from baseline to week 48)


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