SNPMiner Trials by Shray Alag

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SNPMiner SNPMiner Trials (Home Page)


Report for Mutation Y188L

Developed by Shray Alag, 2020-2021.
SNP Clinical Trial Gene

There are 13 clinical trials

Clinical Trials


1 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
Conditions
  1. HIV Infections
Interventions
  1. Drug: matching placebo
  2. 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 --- --- V106M --- --- V106A --- --- V108I --- --- Y181C --- --- Y181C --- --- Y188L ---

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

2 A Phase 2b Study to Select a Once Daily Oral Dose of GSK2248761 in HIV-1 Infected Antiretroviral Therapy Experienced Adults With Non-nucleoside Reverse Transcriptase Inhibitor (NNRTI) Resistance

This 48 week, phase 2b study in 150 HIV-1 infected antiretroviral therapy experienced adult subjects consists of a dose-ranging evaluation of GSK2248761 at blinded doses of 100 mg and 200 mg once daily with a control arm of open-label etravirine (ETV) 200 mg twice daily. The background ART for all three arms will be darunavir/ritonavir (DRV/r) 600 mg/100 mg twice daily plus raltegravir (RAL) 400 mg twice daily. Antiviral activity, safety, PK, and development of viral resistance will be evaluated.

NCT01199731
Conditions
  1. Infection, Human Immunodeficiency Virus
Interventions
  1. Drug: GSK2248761 100 mg once daily
  2. Drug: GSK2248761 200 mg once daily
  3. Drug: Etravirine
MeSH:Infection HIV Infections Acquired Immunodeficiency Syndrome

In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled - HIV-1 genotype results with any of the following will be excluded: (1)Any screening genotype with virus showing a Y181 mutation in combination with any other NNRTI resistance-associated mutations, (2) Any screening genotype with virus showing a Y181I or Y188L alone or in combination with any other NNRTI resistance-associated mutations - HIV-1 phenotype results with any of the following will be excluded: (1) Any screening phenotype with virus showing etravirine fold change >10, (2) Any screening phenotype with virus showing darunavir fold change > 20, (3) Any screening phenotype with virus showing raltegravir fold change >1.5 - Any acute laboratory abnormality at screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound. --- Y181I --- --- Y188L ---

Primary Outcomes

Description: Plasma for quantitative HIV-1 RNA was collected. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 16 has been presented. A 2 ml plasma was assayed with the real-time NucliSens EasyQ HIV-1 assay (bioMerieux) capable of quantifying as low as 2.5 c/mL by using three modifications to the standard assay: 15 microliters (µl) of extracted eluate, 20 µl of primer, and 5 µl of 2X enzyme in place of standard kit volumes. The validated assay incorporated molecular beacons for detection.

Measure: Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies Per Milliliter (/mL) at Week 16

Time: At Week 16

Secondary Outcomes

Description: An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

Measure: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

Description: A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of IP). Division of acquired immunodeficiency syndrome (AIDS) toxicity scale for Grading the Severity of Adult and Pediatric Adverse Events Version 1.0 was used for grading i.e. Grade 3=severe and Grade 4=potentially life threatening. Categories with values have been presented. No toxicity-related dose reductions of IP was allowed. IP and background antiretroviral therapy (ART) was restarted as soon as medically appropriate; in general, this was no longer than 14] days after discontinuation (unless Grade 3 or 4 toxicities persisted).

Measure: Number of Participants With Abnormal Clinical Chemistry Laboratory Data With Grade 3 or 4 Treatment-Emergent (TE) Toxicities

Time: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

Description: A toxicity was considered to be TE if it was greater than the Baseline grade, and if it had developed or increased post-Baseline in intensity (and prior to the last dose of IP). The hematology parameters included hemoglobin, total neutrophils, and white blood cells (WBC) count. Categories with values has been presented. Grade 3=severe and Grade 4=potentially life threatening. No toxicity-related dose reductions of IP was allowed. IP and background ART was restarted as soon as medically appropriate; in general, this was no longer than 14] days after discontinuation (unless Grade 3 or 4 toxicities persisted).

Measure: Number of Participants With Abnormal Hematology Laboratory Data With Grade 3 or 4 TE Toxicities

Time: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

Description: A switch was defined as any ART substitution or addition in the participant's ART regimen. Any ART switch permitted per protocol that was determined necessary and documented prior to the first on-treatment visit where HIV-1 RNA was assessed could occur without penalty. However, any participants with an ART switch not permitted per protocol or ART switch permitted per protocol with a viral load >=50 copies/mL at the time of the decision to switch was made was counted as a non-responder from that point onward for all assessment windows without a viral load measurement collected prior to the switch. Change from Baseline was calculated as (observed value - Baseline value). Baseline was Day 1. The unit is log10 copies per milliliter (log10 copies/mL).

Measure: Change From Baseline in Plasma HIV-1 RNA Prior to Switch of GSK2248761

Time: Baseline (Day 1) and Week 2, 4, 8, 12 and 16

Description: A switch was defined as any ART substitution or addition in the participant's ART regimen. Any ART switch permitted per protocol that was determined necessary and documented prior to the first on-treatment visit where HIV-1 RNA was assessed could occur without penalty. However, any participants with an ART switch not permitted per protocol or ART switch permitted per protocol with a viral load >=50 copies/mL at the time of the decision to switch was made was counted as a non-responder from that point onward for all assessment windows without a viral load measurement collected prior to the switch. Change from Baseline was calculated as (observed value - Baseline value ). Baseline was Day 1.

Measure: Change From Baseline in Plasma HIV-1 RNA After Switch of GSK2248761

Time: Baseline (Day 1) and post switch Week 1, 2, 4, withdrawal and follow-up Week 4, 8, 12

Description: Clinical DP was defined as progression from Baseline HIV disease status:Category A at Baseline to Centers for Disease Control and Prevention(CDC) category B event, category A at Baseline to CDC category C event, category B at Baseline to CDC category C event, category C at Baseline to new CDC category C event or category A, B or C at Baseline to death. Category A consisted of one or more of the conditions like asymptomatic HIV infection, persistent generalized lymphadenopathy and acute (primary) HIV infection with accompanying illness in an adolescent or adult(>13 years) with documented HIV infection. Category B consisted like Bacillary angiomatosis, Candidiasis, oropharyngeal (thrush), Candidiasis, vulvovaginal; persistent, frequent, oral, Herpes zoster etc. Category C included clinical conditions listed like Candidiasis of bronchi, trachea, or lungs, Candidiasis, esophageal, Cervical cancer, Coccidioidomycosis, disseminated or extrapulmonary etc in AIDS surveillance case definition.

Measure: Number of Participants Who Experienced Disease Progression (HIV-associated Conditions, AIDS and Death)

Time: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

Description: CD4 is a receptor for the HIV virus. Most of the damage to an AIDS participant's immune system was done by the virus' destruction of CD4+ lymphocytes. Absolute values of CD4+ cell counts after Switch of GSK2248761 has been presented.

Measure: Absolute Values of CD4+ Cell Counts After Switch of GSK2248761

Time: Baseline (Day 1) and post switch Week 1, 2, 4, withdrawal and Follow-up Week 4, 8, 12

Description: CD4 is a receptor for the HIV virus. Most of the damage to an AIDS patient's immune system is done by the virus' destruction of CD4+ lymphocytes. Change from Baseline was calculated as (observed value - Baseline value). Baseline was Day 1 value.

Measure: Change From Baseline in CD4+ Cell Counts Prior to Switch of GSK2248761

Time: Baseline (Day 1) and Week 2, 4, 8, 12 and 16

Description: CD4 is a receptor for the HIV virus. Most of the damage to an AIDS patient's immune system is done by the virus' destruction of CD4+ lymphocytes. Change from Baseline was calculated as (observed value - Baseline value). Baseline was Day 1 value.

Measure: Change From Baseline in CD4+ Cell Counts After Switch of GSK2248761

Time: Baseline (Day 1) and post switch Week 1, 2, 4, withdrawal and Follow-up Week 4, 8, 12

Description: An AE is defined as any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

Measure: Number of Participants Who Discontinued Treatment Due to AEs

Time: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

Description: Number of participants with ECG of PCI above 480 has been presented. ECG was be performed twice on Day 1 at least 5 minutes apart and following 5 minutes of rest in a semi supine position at ∼1 hour prior to first dose. ECG evaluations at other visits was obtained after dosing, preferably at 2 hours post dosing. An ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT (QTc) intervals was used.

Measure: Number of Participants With Electrocardiograph (ECG) With Values of Potential Critical Concern (PCI)

Time: Up to follow-up i.e. 2-4 weeks after the last study visit (due to early termination the last visit was on 19 July 2011)

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
Conditions
  1. HIV Positive
Interventions
  1. Drug: darunavir/cobicistat
  2. 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 ---

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

4 A Randomized Comparative Phase II Trial Evaluating the Capacity of the Dual Combination Doravirine/Raltegravir to Maintain Virological Success in HIV-1 Infected Patients With an HIV-RNA Plasma Viremia Below 50 Copies/mL Under a Current Antiretroviral Regimen

The objective of antiretroviral therapy (ART) is the maintenance of HIV viral suppression, the optimal condition to prevent disease progression, to optimize immune restoration, to prevent the development of viral resistance and to reduce viral transmission. Antiretroviral therapy has to be maintained long life over decades in the absence of strategies for HIV cure. This is why the long-term cumulative toxicity of ARV drugs is a major issue. Indeed as a consequence of potent ART strategies, in 2011 over 88% of patients on ART in the French Hospital database (ANRS CO4 FHDH) achieved viral suppression with HIV-RNA plasma viral load < 50 copies/mL and nearly 60% had CD4 > 500/mm3. As a consequence of massive reduction of mortality and morbidity related to HIV, infected patients are aging with 40% of patients over 50 years of age in the ANRS CO4 FHDH. The current standard-of-care for antiretroviral therapy consists in a triple drug combination with two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a non-nucleoside reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or an integrase inhibitor (INSTI). NRTIs and PIs have been associated to cumulative long-term toxicity such as bone and renal disorders related to tenofovir and increased cardio-vascular risk with PIs. In general population, aging is associated with well-known comorbidities such as bone demineralization, increased incidence of cardio or cerebrovascular disease, diabetes, renal dysfunction. HIV infected patients are at a greater risk for such abnormalities. Another crucial concern is the high probability of drug-drug interactions in HIV-infected patients, between ART and comedications. Alternative strategies are needed, which must address the following questions: how to maintain the control of HIV viral replication while minimizing the occurrence of long-term clinical and metabolic complications, and minimizing the risk of drug-drug interactions? This study is an open label, randomized, switch study over 96 weeks in which virally suppressed patients on a stable combined ART regimen will be randomized (2:1) to an immediate switch to doravirine/raltegravir (immediate switch group) or to the maintaining of their current ART followed by a switch to doravirine/raltegravir at W48 (delayed switch group). Patients will be followed during 96 weeks.

NCT04513626
Conditions
  1. HIV Infections
Interventions
  1. Drug: DORAVIRINE 100 MG [Pifeltro]
MeSH:HIV Infections

- Mutations associated to doravirine resistance are: V106A/M, Y188L, G190E/S, M230L, F227C, at least 2 among: A98G, L100I, K101E, V106I, E138K, Y181C/V, G190A or H221Y - Mutations associated to raltegravir resistance are: T66A/K, E92Q, G118R, F121Y, G140A/S Y143A/C/G/H/R/S, Q148E/G/H/K/R, V151L, N155H/S/T, E157Q, S230R, R263K, L74 F/I + V75I. --- V106A --- --- Y188L ---

Primary Outcomes

Description: Measure of plasma viral load assessed by RNA quantification using COBA 6800 system (Roche)

Measure: Measure the virological efficacy at week 48 of once daily doravirine plus raltegravir dual therapy to assess the effectiveness of the dual therapy DORAL to maintain the virological success to W48

Time: 48 weeks

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
Conditions
  1. HIV Infections
  2. Heroin Dependence
Interventions
  1. 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 --- --- Y188L ---

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 Strategic Study of Dual-therapy With Darunavir/Ritonavir and Rilpivirine QD Versus Triple-therapy in Patients With Suppressed Viral Load: Virological Efficacy and Evaluation of Non-HIV Related Morbidity.

Clinical approach to HIV infection treatment is based on the use of highly active antiretroviral therapies (HAART) and recent national and international guidelines for guiding HIV therapy recommend the use of triple-combination therapy using antiretrovirals with 2 nucleos(t)ide inhibitors [N(n)RTI] as backbone plus a third drug to be chosen among a boosted protease inhibitor (PI/r), a nonnucleoside inhibitor (NNRTI) or an integrase inhibitor (II). In spite of evident efficacy of HAART, as demonstrated by survival increasing, long term side effects, as for example the impact on renal function, remain principal problem. In patient with risk factor for renal disease, a reduction of eGRF (estimated Glomerular Filtration Rate) between 90 and 60 mL/min/1,73 m2 could be already considered as a risk condition [1,2]. Efficacy of HAART, with increase of media survival and the parallel decrease of mortality, has underlined the necessity to reflect on long term HAART effects [3]. There are many evidences of HAART-related toxicity that, in spite of the necessity of a life-saving therapy, focus on the additional costs of this situation, in terms of health as well as in terms of economic costs. Particular attention has been focused on the impact of some drugs on renal function, as tenofovir, especially on tubule, without forgetting the modification of lipid and bone metabolisms. According to further studies which have evidenced the potential of some recently introduced molecules [4,5], the investigators had the need to realize a study to deepen the feasibility of a dual-therapy that permit to exclude NRTIs from the backbone, with the aim to prevent NRTIs-related long-term toxicity. The investigators have designed a prospective randomized controlled trial, open-label, with a duration of 96 weeks, to compare the efficacy of a dual-therapy based on rilpivirine 25mg plus darunavir 800mg/ritonavir 100mg QD, in HIV-positive subjects with suppressed viremia from at least 3 months. In fact, there are a few data about association of these drugs, which it has been shown to be safe, well tolerated, and with a strong pharmacological synergy, without nucleos(t)idic backbone, while the necessity to minimize the costs toxicity-related is becoming increasingly compelling. According to clinical experience and literature data, the investigators hope this study shows positive results in term of immune-virological efficacy, as well as in term of decrease of VACS index - a complex parameter which has the purpose to quantify general organic decay - and markers of lipid and bone metabolism, in group which receives dual-therapy versus the group with standard therapy.

NCT01792570
Conditions
  1. Human Immunodeficiency Virus
Interventions
  1. Drug: RPV + DRV/r
  2. Drug: continue the PI/r-containing HAART.
MeSH:Acquired Immunodeficiency Syndrome HIV Infections

Exclusion Criteria: - Previous drug resistance genotypic test showing the presence of any RPV (RT: K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C, M230I/L) or DRV (protease: V11I, V32I, L33F, I47V, I50V, I54M/L, T74P, L76V, I84V, L89V) resistance associated mutation (RAM), according to the November 2011 IAS-USA list; - Child-Pugh C or grade 3-4 AST or ALT values; - Acute cardiovascular event within 6 months; - AIDS event within 6 months; - Current IVDU; - HBsAg +; - Pregnancy or lactation. --- K101E --- --- E138A --- --- V179L --- --- Y181C --- --- Y188L ---

Primary Outcomes

Description: Responders: HIV+ subjects with HIV-RNA < 50 cp/mL at week 48 according to the intention-to-treat (ITT-TLOVR) approach.

Measure: HIV-RNA < 50 cp/mL

Time: Week 48

Secondary Outcomes

Description: Safety will be assessed through the number of ACTG grade III and IV in the specified safety parameters.

Measure: ACTG grade III and IV events.

Time: over 96 weeks.

7 A Randomized, Blinded, 12-week Comparison of Elvucitabine/Efavirenz/Tenofovir Versus Lamivudine/Efavirenz/Tenofovir in HIV-1 Infected, Treatment Naive Subjects. There is a 36 Week, Open Label, Extension Phase for Eligible Subjects.

Elvucitabine is a novel nucleoside analog that is being studied as a treatment for patients infected with HIV-1. This Phase II study will enroll 60 HIV-1 naive subjects to assess the efficacy and safety of elvucitabine compared to lamivudine in combination with tenofovir and efavirenz measured by changes in the patient's HIV-RNA level and CD4 cell count. The study treatment will be 12 weeks of blinded study medication followed by an additional 84 weeks of open label treatment if the patient's response to treatment meets certain endpoints. Also there will be assessment of the pharmacokinetics of elvucitabine during the study.

NCT00350272
Conditions
  1. HIV Infections
Interventions
  1. Drug: elvucitabine
  2. Drug: Lamivudine
  3. Drug: Tenofovir
  4. Drug: Efavirenz
MeSH:HIV Infections

2. Are 18 through 65 years old 3. Have documented HIV-1 infection by written prior history and clinically stable with no AIDS-defining events in the 3 months prior to Screening 4. Have plasma HIV-1 RNA levels greater than or equal to 5000 copies/mL at Screening 5. Are HIV-1 strain sensitive to elvucitabine, lamivudine, emtricitabine as demonstrated by the absence of the M184V, M184I, and D237E mutations by TRUGENE HIV-1 Genotyping Kit 6. Are HIV-1 strain genotypically sensitive to efavirenz (negative for K103 and Y188L mutations) and tenofovir (negative for K65R mutation) by TRUGENE HIV-1 Genotyping Kit 7. Have a CD4 count greater than or equal to 200 cells/mL and less than 500 cells/mL 8. Have acceptable hematologic and chemistry parameters, including the following: - Hemoglobin (Hgb) greater than or equal to 11g/dL - Absolute neutrophil count greater than or equal to 2000 cells/mm3 - Platelets greater than or equal to 125 000/mm3 - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 1.5 times the upper limit of normal - Total bilirubin less than or equal to 1.5 times the upper limit of normal - Creatinine within normal range 9. Are capable of understanding and has signed the informed consent document 10. --- M184V --- --- M184I --- --- D237E --- --- Y188L ---

Subjects must be genotypically sensitive to efavirenz (negative for K103 or Y188L mutations) and tenofovir (negative for K65R mutation) as demonstrated by TRUGENE HIV-1 Genotyping Kit. --- Y188L ---

Primary Outcomes

Description: Proportion of subjects having achieved a virologic response for elvucitabine 10 mg/day in combination with efavirenz and tenofovir in HIV-1-infected subjects over 12 weeks compared with the proportion of subjects having achieved a virologic response for lamivudine 300 mg/day in combination with efavirenz and tenofovir. Virologic response was defined as having achieved undetectable (<50 copies/mL) HIV-1 RNA levels from baseline assessment.

Measure: The Proportion of Subjects With Virologic Response for 10 mg/Day Elvucitabine in HIV-1-infected Subjects by 12 Weeks Compared With the Proportion of Subjects With Lamivudine 300 mg/Day.

Time: 12 Weeks

Description: Determination of the safety profile of elvucitabine as defined by the frequency, type and severity of treatment-emergent adverse events and the frequency of Grade 3 and Grade 4 laboratory abnormalities.

Measure: The Safety Profile of Elvucitabine.

Time: 12 Weeks

8 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
Conditions
  1. HIV
Interventions
  1. 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 --- --- Y181C --- --- Y188L ---

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

9 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
Conditions
  1. HIV Infection
  2. Hepatitis C
Interventions
  1. Drug: Kaletra (lopinavir/ritonavir)
  2. Drug: Sustiva (efavirenz)
  3. 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 --- --- V106A --- --- V108I --- --- Y181C --- --- Y188L ---

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

10 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
Conditions
  1. HIV Infection
  2. HAART-treated
  3. Virologically Controlled
Interventions
  1. Drug: Arm 1 (intervention)
  2. 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 ---

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

11 Randomised, Double-blind, Placebo-controlled 7 Day Monotherapy Phase IIa Study to Evaluate the Antiviral Activity and Safety of Increasing Doses of Oral Administered RTV-boosted BILR 355 BS (75 mg and 150 mg Twice Daily) in HIV-1-infected, NNRTI-experienced Patients, Followed by 28 Day Combination Therapy With Tipranavir or Lopinavir Based HAART-regimen

The general aim is to evaluate the antiviral activity and safety of increasing doses of oral administered RTV-boosted BILR 355 BS (75 mg and 150 mg twice daily) in HIV-1-infected, NNRTI-experienced patients, followed by 28 day combination therapy with Tipranavir or Lopinavir based HAART-regimen

NCT00294372
Conditions
  1. HIV Infections
Interventions
  1. Drug: BILR 355 BS
  2. Drug: Placebo
MeSH:HIV Infections

The following resistance mutations demonstrated at any time prior to starting trial therapy: V106A and/or Y188L 2. Female patients of child-bearing potential who: have a positive serum pregnancy test at screening or during the study, are breast feeding, are planning to become pregnant, are not willing to use a barrier method of contraception. --- V106A --- --- Y188L ---

Primary Outcomes

Measure: The primary endpoint will be reduction in plasma HIV-1 RNA from baseline to day 8, expressed in log10 copies/mm3.

Time: day 8

Secondary Outcomes

Measure: Virologic response at Day 8 and Day 35 using <400 copies/mL and 0.5, 1 and 1.5 log10 reduction in viral load from baseline

Time: up to week 5

Measure: Change from baseline in viral load at each visit

Time: up to week 9

Measure: Change from baseline in CD4+ cell counts at each visit

Time: up to week 9

Measure: Time averaged change from baseline in viral load through Days 8 and 35

Time: up to week 5

Measure: Number of reverse transcriptase (RT) mutations at baseline

Time: up to week 5

Measure: Number of NNRTI resistance-associated mutations at baseline (refer to Appendix 10.4)

Time: up to week 5

Measure: The presence of specific RT mutations (both in the list of NNRTI mutations and not in the list for exploratory purposes) at baseline

Time: up to week 5

Measure: The inhibitory quotient and minimum measured concentration of the analyte in plasma (Cmin)

Time: up to Day 8

Measure: Exploration of mutations that emerge with exposure to BILR 355 BS to determine the effect on both viral load and IC50 fold change from reference

Time: up to week 5

Measure: Area under the concentration-time curve of the analyte in plasma over the time interval 0 to 12 hours post-dose (AUC0-12h)

Time: up to week 5

Measure: Maximum measured concentration of the analyte in plasma (Cmax)

Time: up to week 5

Measure: Changes in total cholesterol, LDL, HDL and triglycerides from baseline to days 8 and 35

Time: up to week 9

Measure: Incidence of rash, hepatic events, and CNS adverse events

Time: up to week 9

Measure: Incidence of any adverse events (treatment related and unrelated)

Time: up to week 9

Measure: Incidence of laboratory test abnormalities

Time: up to week 9

Measure: Incidence of serious adverse events (including AIDS-defining events)

Time: up to week 9

Measure: Incidence of ≥ DAIDS 2 Grade elevation in ALT/AST

Time: up to week 9

Measure: Incidence of AEs leading to discontinuation from the study

Time: up to week 9

12 Explorations Into the Mechanism for INSTI-associated Weight Gain: a Focus on Energy Balance

Weight gain following antiretroviral therapy (ART) initiation occurs with all modern regimens. Recent real-world reports suggest that integrase strand transfer inhibitor (INSTI)-based ART may be associated with excess weight gain compared to other regimens. Weight gain appears to occur regardless of baseline weight, and is most pronounced among women and minorities, often those at highest risk of obesity-associated comorbidities. INSTI- and TAF-based regimens are now preferred regimens for most persons according to the Department of Health and Human Services ART-Treatment Guidelines. As a result, there is an urgent need to understand the underlying mechanisms for this weight gain. This study aims to understand the changes in energy balance that occur with changes in ART. Participants with HIV who have experienced >10% weight gain on INSTI (bictegravir or dolutegravir-based therapy) will be switched to doravirine for 12 weeks, and then back to their prior INSTI regimen, allowing for assessment of changes in metabolic parameters with drug withdrawal and reintroduction (with no change to NRTI-backbone). Twenty-four hour energy balance will be measured on both regimens during a 24-hour stay using a whole room indirect calorimetry, with a standardized diet. Ultimately, the investigator's goal is to understand the mechanisms of weight gain so that future interventions can most effectively mitigate ART-associated weight changes.

NCT04495348
Conditions
  1. HIV-1-infection
  2. Weight Gain
Interventions
  1. Drug: Doravirine
MeSH:Body Weight Weight Gain
HPO:Increased body weight

- Severe claustrophobia that would limit ability of participant to remain in the whole room calorimeter - Known resistance to any component of the study drugs, including detection of any of the following resistance mutations on prior HIV genotype test (genotype testing not required if not available): Doravirine resistance: V106A, V106I, V106T, V106M, Y188C, Y188H, Y188L, G190E, P225H, F227C, F227L, F227R, M230L, L234I Resistance to NRTIs: K65R, K65E, K65N, T69S (insertion complex), K70E, L74V, Y115F, Q151M, M184I, M184V. --- V106A --- --- V106I --- --- V106T --- --- V106M --- --- Y188C --- --- Y188H --- --- Y188L ---

Primary Outcomes

Description: Change in total energy expenditure (kcal/day)

Measure: Change in energy balance

Time: 24 weeks

13 A Phase 3b Randomized, Open-label, Controlled Study of the Efficacy, Safety and Tolerability of 12 Weeks of Ledipasvir/Sofosbuvir (LDV/SOF) Treatment for HIV/HCV Co-infected Subjects Who Switch to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) or Emtricitabine/Rilpivirine/Tenofovir Alafenamide (F/R/TAF) Prior to LDV/SOF HCV Treatment, the HIV/HCV Co-STARs Study (Co-infection Treatment With Single Tablet Antiviral Regimens)

This study will evaluate efficacy of ledipasvir/sofosbuvir (LDV/SOF) and safety and tolerability of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or emtricitabine/rilpivirine/tenofovir alafenamide (F/R/TAF) from the current antiretroviral (ARV) therapy and in virologically-suppressed, HIV-1/HCV co-infected participants.

NCT02707601
Conditions
  1. HIV-1 Infection
  2. HCV Infection
Interventions
  1. Drug: E/C/F/TAF
  2. Drug: F/R/TAF
  3. Drug: LDV/SOF
MeSH:Infection Communicable Diseases Hepatitis C

- Plasma HIV-1 RNA level < 50 copies/mL at the screening visit - Have no documented resistance to any of the HIV study agents at time in the past, including but not limited to the reverse transcriptase resistance mutations K65R, K70E, K101E/P, E138A/G/K/R/Q, V179L, Y181C/I/V, M184V/I, Y188L, H221Y, F227C, M230I/L, the combination of K103N+L100I, or 3 or more thymidine analog associated mutations (TAMs) that include M41L or L210W (TAMs are M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). --- K65R --- --- K70E --- --- K101E --- --- E138A --- --- V179L --- --- Y181C --- --- M184V --- --- Y188L ---

Primary Outcomes

Description: Sustained Virologic Response (SVR12) was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping LDV/SOF treatment.

Measure: Percentage of Participants With HCV RNA < LLOQ at 12 Weeks After Discontinuation of LDV/SOF Treatment (SVR12)

Time: HCV Posttreatment Week 12

Secondary Outcomes

Description: SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping LDV/SOF treatment.

Measure: Percentage of Participants With HCV RNA < LLOQ at 4 Weeks After Discontinuation of LDV/SOF Treatment (SVR4)

Time: HCV Posttreatment Week 4

Description: The percentage of participants with HIV-1 RNA ≥ 50 copies/mL 24 weeks after start of the F/TAF-based regimen were analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.

Measure: Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL (Virologic Failure) 24 Weeks After Start of the F/TAF-Based Regimen Using Modified FDA Snapshot Algorithm

Time: 24 weeks after start of HIV treatment

Measure: Percentage of Participants Experiencing Grades 1 Through 4 Adverse Events After Switch to E/C/F/TAF or F/R/TAF Throughout the Study and During Coadministeration With LDV/SOF Treatment

Time: Up to 32 weeks plus 30 days


HPO Nodes


HP:0004324: Increased body weight
Genes 585
NTRK2 BLK MERTK SH2B1 PROK2 FIBP MAGEL2 FEZF1 MEGF8 ALG13 MEN1 CUL4B MAGEL2 BBIP1 AGTR2 ZNF711 GTF2IRD1 SLC9A7 SLC7A14 RP1 OFD1 CEP164 PHF21A FRMPD4 BRAF RTL1 PHF6 BBS1 FGFR3 KCNJ11 CNNM2 GNAS PDE6A MTOR CNGB1 ARVCF HACE1 LIPE ZNF408 UCP2 HNF4A WDR11 CTNNB1 EIF2S3 RREB1 TOPORS IFT172 OCA2 IFT172 LZTFL1 KCNJ11 RBP3 RYR1 ERMARD ARX AP4B1 SAG TMEM43 PAX4 ATP10A CEP290 UBE3A NDN NDN SYNE1 BBS10 H6PD DMD RAB39B FLRT3 PROKR2 RTL1 PCNT SIM1 TTC8 CLIP2 ABCC8 ELN TBX3 IGF1R HIRA GP1BB GNAS DIS3L2 VPS13B OFD1 BAP1 EMD ADNP SEC24C ELN KLF11 TULP1 KIDINS220 GNAS THOC2 KIF7 PIGA RNPC3 GHR SNRNP200 CLCN4 P4HTM AKT2 AP4M1 IGSF1 PRMT7 IFT74 GDI1 NEUROD1 TRIP4 SIN3A RTL1 HESX1 PTCHD1 DLK1 C8ORF37 PDE4D WNT4 SUFU CREBBP NPAP1 PDE4D PIGT VPS13B SDC3 BBS4 SLC7A7 PTCH1 ARL6 RP9 IFT88 TMEM67 SLC10A7 RHO CD46 MYT1L BLM PDX1 NPHP1 ARL3 IFT27 RPGR MYF6 FGFR1 PDE6B DLK1 ATP6AP2 MEG3 MC3R ZNF365 HNF4A SNORD115-1 ZNF513 THRA SRY BBS10 SOX3 SPRY4 RLBP1 RAB23 MKRN3-AS1 TSPAN7 AP4E1 ACADVL PDSS1 FAM161A FTSJ1 ROM1 PCSK1 AP4S1 SNRPN TTC8 FGF17 ABCC8 MAPK8IP3 SH2B1 IGF1 ZNF81 HUWE1 IDH3B BBIP1 PDE4D USP8 CACNA1S EGF FHL1 USP8 BEST1 KMT2A GNAS PWRN1 TBX3 IPW RP2 WDPCP KMT2D XYLT1 BBS9 ARNT2 APPL1 SUFU CHD8 FGF8 PAK3 IMPDH1 SNRPN MEGF8 DHDDS EIF2S3 BAP1 GCK RAI1 MCM3AP SH2B1 HNF1A RPE65 SNRPN ZBTB20 SMARCB1 NKAP SPATA7 HDAC8 P2RY11 WT1 XRCC4 PRMT7 ARHGEF18 BBS9 ABCC8 POMC HLA-DQB1 HS6ST1 TRIM32 WT1 CREBBP CANT1 OCA2 NR0B2 UBE2A THOC2 LMNA KLHL7 STX16 SDCCAG8 RAD21 ALMS1 SEMA4A USH2A CERKL FMR1 TRAF7 CYP19A1 PAX6 TNFSF4 PTEN ODC1 FGFR1 BBS7 DDX6 AFF4 MAGEL2 ACSL4 CHD7 CCDC141 PCNT PRPF8 MID2 DNM2 GABRA3 BBS7 HNF1A KDM6A CDHR1 SNRPN HLA-DRB1 DYNC2I2 UBE3A TRIM32 MAGEL2 PWAR1 TRIP12 KCNJ11 EYS BRAF SYNE2 ARL6 SHOX TACR3 CNKSR2 CEP19 CLRN1 NIPBL SMAD4 NDN MTTP TCF20 USP9X MKRN3 ADRB3 SETD2 CFI OCA2 MRAP2 ENPP1 DHX38 IFT172 ADRB2 RTL1 CARTPT CUL4B SMO SNRPN PIGN DLK1 LEP CYP7A1 ARL2BP MAN1B1 PRCD IL1RAPL1 PRPH2 CDH23 NEK2 ODC1 NSMF NDN PIGL REEP6 JMJD1C CREBBP AGBL5 PDGFB PROM1 TBX1 MTFMT MECP2 MAN1B1 GNAS LEPR TBL2 POMC SIM1 TBX1 BBS2 PIGT HERC1 SDCCAG8 SPG11 EHMT1 IFT140 PNKP MTOR MEG3 FOXP1 PSMD12 RFC2 TMCO1 GATA4 SNORD116-1 LEPR MKKS LMNA LIMK1 BLK MED12 BBS12 MKS1 PCSK1 SMARCE1 ABCA4 IDH3A EP300 BBS1 KIZ ATRX BBS5 BDNF TRAPPC9 IMPG2 HESX1 MKS1 PDE11A SIN3A SOX10 MAGEL2 SYP RPS6KA3 TBX1 ZNF41 KISS1R MEG3 STEEP1 IQSEC2 TRAF3IP1 TUB TAF1 ATRX PRDM16 UBE3A CFH C8ORF37 DEAF1 LEP AFF4 UBE3A RAB23 DNMT3A COA3 RTL1 USP27X IQSEC2 GHRL BPTF LAS1L INS RAI1 ARL13B PHIP EXOC6B MECP2 SNRPN RERE OTX2 RBMX SIM1 PNPLA6 SKI WAC DPYD POGZ DCC IL17RD FIBP POMGNT1 PDE6G GLI3 HDAC4 SLC25A4 ALMS1 POU3F4 AKT2 PAX6 CCDC141 TRAPPC9 SEMA3A AHI1 MC4R HACE1 TERT BBS2 PKDCC PIK3CA GABRD TP53 ARMC5 RP1L1 EHMT1 CRB1 CNGA1 EHMT1 ANOS1 NF2 ABCC9 ANK3 LARS2 UFD1 HGSNAT SH3KBP1 HNF4A ARMC5 UCP3 CCDC28B GTF2I MAGEL2 HSD11B1 SHANK3 BBS5 PRPF3 GUCA1B INPP5E PPARG IGFALS FTO GNAS SETD5 ARL6 BBS4 RAI1 XYLT1 TTC8 NR2E3 PCARE IFT172 MAK MEG3 ADCY3 RNF135 UPF3B SMC1A NDN PROK2 SOX2 DUSP6 POMC HCFC1 COL10A1 MKKS SMC3 FSCN2 ADNP GNAS-AS1 CA4 ALB MC4R PRKACA NIN SNRPN IFT27 AKT1 RGR AHR PRPF4 MOG HDAC8 HERC2 ZNF711 TUB NDNF LRAT CEP290 DLG3 MTMR14 DYRK1B SCAPER CRX EP300 DLK1 KIAA1549 KCNJ18 MAGEL2 PROKR2 MLXIPL KIDINS220 MEG3 FXR1 LZTFL1 BBS12 PRPF31 IQSEC2 KMT2C PRPF6 AGRP ATP7B HCRT BBS2 DLK1 MOG APOE BIN1 HELLPAR GNAS NRL PRKAR1A BAZ1B LAS1L RDH12 ARL6 COMT HDAC8 USP7 FLII ARHGEF6 FOXP1 AIP KCNAB2 C8ORF37 PHF6 GNAS RPS6KA3 PRKAR1A EDNRB CTSH CEL OCA2