SNPMiner Trials by Shray Alag


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Report for Mutation Y181V

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 3 clinical trials

Clinical Trials


1 A Multicenter, Single Arm, Open-Label Study of the Once Daily Combination of Etravirine and Darunavir/Ritonavir As Dual Therapy in Early Treatment-Experienced Patients

This study is a Phase II single arm, open-label, multicenter, study of 50 human immunodeficiency virus-1 (HIV) infected adult patients, all of whom will receive etravirine (ETR) 400mg and DRV/r 800/100mg each given orally once daily. This trial is designed to evaluate the efficacy of the aforementioned ARV regimen, as measured by the percentage of patients with HIV RNA <50 copies/mL at 48 weeks, in early treatment-experienced HIV-infected patients. In addition to general safety parameter measurements, this trial will also assess changes in metabolic, inflammatory, immune restoration, and bone markers. Screening will occur over a 6-week period. The primary endpoint will be assessed at Week 48, and the treatment period is 48 weeks. The end of study endpoint will be met by either completing the Week 48 visit, or by early termination from the study for any reason.

NCT01199939 Human Immunodeficiency Virus (HIV) Drug: Etravirine Drug: Ritonavir Drug: Darunavir
MeSH:Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes
HPO:Immunodeficiency

Inclusion Criteria: - Male or female patients, aged 18 years or above - Patients with documented HIV-1 infection - On current HAART regimen for at least 12 weeks continuous duration at screening, and with an HIV-1 plasma viral load above 500 HIV-1 RNA copies/mL by site's currently utilized viral load assay (Note: For the purposes of this study, HAART is defined as treatment with a combination of 3 or more HIV antiretroviral medications from at least 2 different classes of medications (NRTIs, NNRTIs, PIs, integrase inhibitors, CCR5 antagonists, fusion inhibitors)) - No more than 2 previous virologic failures while on PI-containing HAART regimens where virologic failure is generally defined as either a lack of suppression of the subjects' viral load to lower limit of quantification (per standard assay historically used in care) after 24 weeks of treatment or, rebound of a previously suppressed viral load (undetectable per investigator's standard of care) to detectable limits and without demonstrated re-suppression on the same regimen - Demonstrated phenotypic sensitivity to both etravirine and darunavir based on resistance testing at Screening (FC= 2.9 for etravirine and FC = 10.0 for darunavir using the PhenoSense GT) - The absence of all of the following Resistance Associated Mutations (RAMS) at baseline: For Darunavir: V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, L76V, I84V, L89V - For Etravirine: L100I, E138A, I167V, V179D, V179F, Y181I, Y181V, G190S - 7. CD4 count = 50 cells/mm3. --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54L --- --- T74P --- --- L76V --- --- I84V --- --- L89V --- --- L100I --- --- E138A --- --- I167V --- --- V179D --- --- V179F --- --- Y181I --- --- Y181V ---

Primary Outcomes

Description: CVR is defined as confirmed plasma Viral Load of less than 50 human immunodeficiency virus - type 1 (HIV-1) ribonucleic acid (RNA) copies/mL.

Measure: Number of Participants With Confirmed Virologic Response (CVR) at Week 48

Time: Week 48

Secondary Outcomes

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 4

Time: Baseline (Day 1) and Week 4

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 8

Time: Baseline (Day 1) and Week 8

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 12

Time: Baseline (Day 1) and Week 12

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 16

Time: Baseline (Day 1) and Week 16

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 20

Time: Baseline (Day 1) and Week 20

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 24

Time: Baseline (Day 1) and Week 24

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 30

Time: Baseline (Day 1) and Week 30

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 36

Time: Baseline (Day 1) and Week 36

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 42

Time: Baseline (Day 1) and Week 42

Measure: Change From Baseline in Log10 Plasma Human Immunodeficiency Virus - Type 1 (HIV-1) Viral Load at Week 48

Time: Baseline (Day 1) and Week 48

Description: CVR is defined as confirmed plasma Viral Load of less than 50 human immunodeficiency virus - type 1 (HIV-1) ribonucleic acid (RNA) copies/mL.

Measure: Time to Reach First Confirmed Virologic Response

Time: Baseline (Day 1) to Week 48

Description: Virologic Failure is defined as participant who is a rebounder or a non-responder. Rebounder participant is defined as a participant who is still in the study at Week 12 and first achieves 2 consecutive virologic responses (<50 copies/mL) followed by 2 consecutive non-responses or a discontinued participant (any reason) for which the last observed time point shows a non-response. Non responder participant is defined as a participant who is still in the study at Week 12 and never achieves 2 consecutive responses.

Measure: Number of Participants With Virologic Failure

Time: Baseline (Day 1) to Week 48

Measure: Change From Baseline in Cluster of Differentiation 4 (CD4+) and Cluster of Differentiation 8 (CD8+) Cell Counts at Week 48

Time: Baseline (Day 1) and Week 48

2 A Phase IV, Open-label Single-arm Study Investigating the Pharmacokinetics and Pharmacodynamics of the Antiretroviral Combination of Rilpivirine and Ritonavirboosted Darunavir in Therapy-naive HIV-1 Infected Patients.

For patients who are starting to take antiretroviral medication (to treat HIV) for the first time, there are now a variety of different medicines which may be taken together as a combination in order to form an effective treatment which suppresses the virus for prolonged periods of time. Currently, national guidelines recommend the use of two different drugs of one type (the nucleoside/ nucleotide reverse transcriptase inhibitors, NRTI often known as "nukes") with a third drug from one of two other types (either a nonnucleoside reverse transcriptase inhibitor, known as an NNRTI or "nonnuke", or a protease inhibitor, known as a PI) to form a treatment regime of three active drugs. In the UK and Europe, all PIs are given in combination with a small dose of a second PI, ritonavir, which has the effect of boosting the levels of the active PI in the bloodstream. The investigators know from both research studies and patient experience in clinic that a combination of a ritonavirboosted PI with an NNRTI achieves similar results in suppressing the HIV virus, compared to the use of either a PI or NNRTI with 2 NRTI as described above. In this study, the investigators will observe the combination of two licensed antiretroviral medications, ritonavirboosted darunavir(DRV/r) and rilpivirine (RPV), in suppressing virus when given to patients who are commencing treatment for HIV infection for the first time. Both of these drugs are licensed for treatment of patients with HIV in the UK and Europe, and are currently in standard clinical use. The study will monitor this treatment over the first 48 weeks. The investigators will also examine the levels of both drugs in the bloodstream during the first 4 weeks of starting this regimen, to confirm that they remain at levels which the investigators know to be effective against the virus.

NCT01736761 HIV Drug: Darunavir, Ritonavir and Rilpivirine

- Disallowed concomitant medication as per the summary of product characteristics for darunavir or rilpivirine (see section 5.2). - Any genotypic resistance mutations on screening or prior tests to darunavir (V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V) or rilpivirine (K101E, K101P, E138A, E138G, E138K, E138R, E138Q, V179L, Y181C, Y181I, Y181V, H221Y, F227C, M230I, and M230L). --- V11I --- --- V32I --- --- L33F --- --- I47V --- --- I50V --- --- I54M --- --- I54L --- --- T74P --- --- L76V --- --- I84V --- --- L89V --- --- K101E --- --- K101P --- --- E138A --- --- E138G --- --- E138K --- --- E138R --- --- E138Q --- --- V179L --- --- Y181C --- --- Y181I --- --- Y181V ---

Primary Outcomes

Description: To describe the rate of virologic suppression after 48 weeks of therapy with the study regime. This will be measured by the proportion of patients with HIV-1 RNA ≤ 40 copies/mL at week 48

Measure: Virologic suppression after 48 weeks of therapy with the study regime

Time: 48 weeks

Secondary Outcomes

Description: The proportion of enrolled patients with a reduction from baseline in HIV-1 RNA >1 log10 copies /mL at weeks 4, 8, 12 and proportion with HIV-1 RNA ≤400 copies/mL at week 24.

Measure: To explore the virologic response to this combination rilpivirine and ritonavir-boosted darunavir at weeks 4, 8, 12 and 24 of therapy.

Time: 24 weeks

Other Outcomes

Description: The PK parameters (Cmax, C24, AUC0-24, and t1/2) for darunavir, rilpivirine and ritonavir at steady-state on day 28

Measure: To investigate the plasma pharmacokinetics of darunavir, ritonavir and rilpivirine when given in combination

Time: Day 28

3 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 ---

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


HPO Nodes


HP:0002721: Immunodeficiency
Genes 267
WHCR EPG5 CTPS1 MBTPS2 TLR3 IL2RG ISG15 CHD1 CLCA4 JAK3 PRKCD AK2 CD40LG FOXN1 NFE2L2 ATRX TNFRSF1B SKIV2L IFNGR1 TTC37 DCLRE1C TBCE BCR ZBTB24 CD3G BSCL2 SDHD XRCC4 LAMTOR2 IKZF1 AGPAT2 CTBP1 LRRC8A RAG2 ANTXR2 SLC46A1 CHD7 TINF2 CR2 IRF7 USP8 CD3E CD3D IL12B TNFRSF13C NHEJ1 IL2RG CD79B TNFSF12 EPG5 CUL4B ICOS LAT MAGT1 IL7R TBX1 TERT UNC93B1 LCK DCLRE1C MTHFD1 HIRA NSD2 CARD9 IRF8 UROS SHANK3 PIK3CD UFD1 NHP2 MYC CD81 CD79A TNFSF12 UNC119 RAG1 LRBA NCF2 LMNB2 BUB1B SEC23B FGFRL1 LYST CDCA7 BLNK RMRP FOS TCF3 RAG1 RBCK1 NFKB2 SIN3A CTLA4 JMJD1C CD81 MEIS2 PGM3 POLE IKBKG ADA IRF8 STAT1 PARN CFTR TNFRSF13C IL21R TNFRSF13B ICOS NFKB1 LIG4 CD28 SIK3 USB1 RAG1 IKBKG ADA DNMT3B RAG2 CR2 STX1A SEC24C SDHC ADA2 BTK IL2RG NCF1 FOXN1 TNFRSF13C LAMTOR2 ACTB SP110 RTEL1 SKIV2L PIK3R1 CDC42 RTEL1 CARD11 DNMT3B SDHB CDH23 HELLS PRKDC PIK3CA TYK2 AP3D1 TRAF3 FRAS1 CORO1A SPATA5 DOCK2 AKT1 RTEL1 XIAP FCGR3A TFRC ACD COMT ACP5 LETM1 RNF168 CD19 PNP POLE CHD1 RMRP AGL STAT1 ARVCF NFKB2 SH2D1A WAS NFKB1 IL21 AK2 IL2RA CDC42 GATA1 PARN ZBTB24 SMARCAL1 STIM1 TNFRSF13B NPM1 COG6 DKC1 CYBA MALT1 MS4A1 ICOS PTEN DCTN4 TINF2 DKC1 LIG4 TBX1 CR2 PRPS1 RAG1 UNG CAV1 HYOU1 RAC2 LYST IRAK4 RAB27A TNFRSF4 TGFB1 FCN3 USF3 HBB CCDC47 IFNGR2 RREB1 IRAK4 IKBKG CD19 CAVIN1 RAG2 PPARG AICDA IKBKB CD40 PGM3 PKP1 KLLN MYD88 CPLX1 EXTL3 MMUT XIAP STAT1 ORAI1 IKBKG CD19 CD247 TBK1 CYBB PIK3R1 TICAM1 CTC1 WRAP53 GP1BB TTC7A TTC7A NOP10 RNF168 BCL10 MAPK1 WIPF1 MS4A1 IL12RB1 TERC DKC1 BCL11B XRCC4 IGHM STK4 IL7R PTPRC IGLL1 CRKL IL2RB ATM IRF2BP2 GATA2 SPATA5 TERT
SNP 0