SNPMiner Trials by Shray Alag


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Report for Mutation Q151M

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 15 clinical trials

Clinical Trials


1 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Exploring the Safety, Tolerability, and Antiviral Effect of Substituting 600 mg Racivir for 3TC in HIV-Infected Subjects Who Have the M184V Mutation and Are Currently Failing on a HAART Regimen Containing Lamivudine

Racivir ® (RCV) is an experimental drug which means it is not approved for use by the United States Food and Drug Administration (FDA), but it can be used in research studies like this one. RCV (Racivir®) is part of a class of drugs known as "Nucleoside Reverse Transcriptase Inhibitors" (NRTIs), which are intended to block a further increase in the amount of HIV virus in the body. Laboratory research suggests that RCV (Racivir®) may be effective in patients who have developed resistance to other NRTIs, particularly 3TC (lamivudine, Epivir®). However, a study of RCV (Racivir®) has not been done with patients who have previously been treated with other HAART (Highly Active Antiretroviral Therapy -- taking multiple HIV drugs at once) medications including 3TC (lamivudine, Epivir®). The purpose of this study is to evaluate the safety and effectiveness of RCV (Racivir®) when used together with other HIV drugs in people who have previously been treated with 3TC (lamivudine, Epivir®) and are failing with their current HAART treatments. This study will include a total of 60 HIV infected, HAART-experienced subjects currently receiving 3TC (lamivudine, Epivir®) as part of their HAART therapy. The study will take place at approximately 11 study sites in the US and Latin America.

NCT00121979 HIV Infections Drug: Racivir, a non-nucleoside reverse transcriptase inhibitor
MeSH:HIV Infections

- Subjects with Q151M mutation. --- Q151M ---

Primary Outcomes

Measure: Change from baseline in virological response of HIV (log10 HIV-RNA levels) at the end of week 2

Measure: Change from baseline in CD4+ count at the end of week 2

Measure: Adverse events

Secondary Outcomes

Measure: Proportion of subjects in each treatment arm with viral load reduction ≥ 0.5 log10 from baseline

Measure: Proportion of subjects in each treatment arm with viral load below 50 copies/mL

2 Prospective Trial to Evaluate How Therapeutic Drug Monitoring of Protease Inhibitors Increases Virologic Success and Tolerance of HAART (ANRS 111 COPHAR2)

This Cophar2 study is a trial which evaluates repeated early therapeutic drug monitoring, from weeks 2 to 24, after the initiation of HAART including either indinavir/r, lopinavir/r or the new 625 mg formulation of nelfinavir twice-a-day (bid). If trough concentrations were out of the range given for each protease inhibitor (PI), the PI dose was adjusted.

NCT00122590 HIV Infections Drug: nelfinavir Drug: lopinavir/r Drug: indinavir Drug: ritonavir
MeSH:HIV Infections

Inclusion Criteria: - Patients infected with HIV-1 - Needing an antiretroviral treatment according to standard of care - HIV viral load greater than 1000 copies/ml - Beginning a treatment containing a PI (indinavir with or without ritonavir, nelfinavir, lopinavir + ritonavir) and 2 reverse transcriptase inhibitors - PI-naive - Antiretroviral treatment-naive or already treated with reverse transcriptase inhibitors but if the viral genotypic test does not show more than 2 major mutations (including T215Y/F, Q151M, M184V/I, V75M/S, L74V) and if 3 nucleoside analogues are still active except for didanosine. --- T215Y --- --- Q151M ---

Exclusion Criteria: - Pregnant women and nursing mothers - Acute HIV infection - Diabetes - Renal insufficiency with creatinine clearance below 30 ml/min - Cardiac insufficiency - Hepatic insufficiency with TP below 60% - Treatment with known interactions with PI - Chemotherapy against Kaposi's sarcoma, lymphoma, neoplasia - Treatment containing interferon (INF) or interleukin-2 (IL2) or HIV- immune vaccine - Treatment with hypolipemic drugs - Laxative treatment - Previous renal colic - Diarrhoea with more than 5 stools/day since one week Inclusion Criteria: - Patients infected with HIV-1 - Needing an antiretroviral treatment according to standard of care - HIV viral load greater than 1000 copies/ml - Beginning a treatment containing a PI (indinavir with or without ritonavir, nelfinavir, lopinavir + ritonavir) and 2 reverse transcriptase inhibitors - PI-naive - Antiretroviral treatment-naive or already treated with reverse transcriptase inhibitors but if the viral genotypic test does not show more than 2 major mutations (including T215Y/F, Q151M, M184V/I, V75M/S, L74V) and if 3 nucleoside analogues are still active except for didanosine. --- T215Y --- --- Q151M ---

Primary Outcomes

Measure: treatment failure defined as viral load greater than 200 copies/ml between week 16 (W16) and week 48 (W48) (confirmed by 2 samples spiked at least 15 days apart but no more than 45 days after virological failure, assayed by 50 copies/ml method)

Measure: toxicity related to PI, defined as adverse event grade 3 or 4 with ANRS quotation, renal colic, diarrhoea grade 2, or cholesterolemia over 10 times the normal value

Secondary Outcomes

Measure: virological failure: viral load over 200 copies/ml between W16 and W48 (confirmed by 2 samples spiked at least 15 days apart but no more than 45 days after virological failure, assayed by 50 copies/ml method)

Measure: toxicity related to PI: adverse events grade 3 or 4 with ANRS quotation, renal colic, diarrhoea grade 2, or cholesterolemia over 10 times the normal value

Measure: patients with trough plasma concentrations outside the therapeutic range at W24 and W48

Measure: concentration changes with dosage variation

Measure: time to obtain a viral load below 200 copies/ml

Measure: relationship between adverse events grade 3 or 4 related to PI and plasma concentration at week 2 (W2)

Measure: relationship between pharmacokinetic parameters and/or plasma concentrations and the drop of viral load between day 0 (D0) and W2 and between D0 and week 4 (W4)

Measure: relationship between pharmacokinetic parameters and viral mutations occurring during the treatment of patients with virological failure (over 1000 copies/ml after week 24 [W24])

Measure: PI pharmacokinetic parameter estimation and evaluation of variability

Measure: pharmacokinetic variability of nucleoside analogues at W2

Measure: intracellular concentration of nucleoside triphosphate derivatives at W2 (trough and maximum) and relationship between virological response and adverse events

Measure: relationship between inhibitory quotient of indinavir and virological response

3 A Randomized, Double-Blind, Phase II Study Comparing the Anti-Retroviral Safety and Efficacy of Dexelvucitabine (DFC) 200 mg Once Daily to Lamivudine (3TC) 300 mg Once Daily in Addition to Optimized Background Therapy in HIV-1 Infected Subjects Who Have Failed and/or Harbor HIV With Resistance Mutations to NRTIs, PIs, and NNRTIs

The study will compare the safety and efficacy of an investigation nucleoside analog reverse transcriptase inhibitor (NRTI), dexelvucitabine (DFC), to an approved NRTI, lamivudine (3TC) in HIV treatment-experienced patients who are resistant to 3 classes of antiretroviral therapies (NRTIs, PIs and NNRTIs). Patients meeting eligibility requirements will have a new 'optimized' background regimen (OBR) selected for them by their investigator based on prior ARV treatment history and the results of HIV genotype and phenotype tests performed during the screening period. In addition to treatment with the new OBR, patients will be randomized to receive treatment with either DFC or 3TC in a blinded fashion. There is a 50 percent chance a patient will receive DFC or 3TC. Treatment in the study may continue for up to 96 weeks. Patients with an inadequate response to therapy after 16 weeks will have the option to change their OBR and the option to switch to receive the other study medication (i.e., DFC to 3TC or 3TC to DFC).

NCT00300573 HIV Infections Human Immunodeficiency Virus Drug: Dexelvucitabine
MeSH:HIV Infections Acquired Immunodeficiency Syndrome

- Subjects with RT mutations Q151M or T69SS on Screening genotype. --- Q151M ---

Primary Outcomes

Measure: Percent of subjects with >= 1.0 log10 decrease in viral load from Baseline to Week 24 based on non-completer equals failure (NC=F)

Time: Week 48 compared to baseline

Measure: Percent of subjects at 48 weeks with sustained suppression of viral load >= 1.0 log10 below baseline as determined by time-to-loss of virological response (TLOVR)

Time: Week 48 compared to baseline

Secondary Outcomes

Measure: Median change in viral load from Baseline to Week 24 and to Week 48

Time: Week 24 or Week 48 compared to baseline

Measure: Proportion of subjects in each treatment arm with viral load reduction greater than the over all study median viral load reduction

Time: Week 24 and Week 48

Measure: Proportion of subjects with a viral load measurement <400 copies/mL at Week 24 and Week 48

Time: Week 24 and Week 48 compared to baseline

Measure: Proportion of subjects with a viral load measurement <50 copies/mL at Week 24 and Week 48

Time: Week 24 and Week 48 compared to Baseline

Measure: Median change in subset of T lymphocytes (CD4+) cell count from Baseline to Week 24 and Week 48

Time: Week 24 and Week 48 compared to baseline

Measure: Proportion of subjects with a 50% decrease and/or 100 cell/mm3 decrease in CD4+ cell count to Week 24 and to Week 48

Time: Week 24 and Week 48 compared to baseline

Measure: Proportion of subjects who "crossed-over" to receive treatment with the other blinded study medication

Time: Week 16 and visits thereafter

Measure: Number of Centers for Disease Control (CDC) Class C adverse events and deaths by treatment arm

Time: approximately every 2 to 4 weeks for laboratory testing

4 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 --- --- Y181C --- --- Y188L --- --- G190S --- --- M41L --- --- Q151M ---

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

5 Preservation and Expansion of T-cell Subsets Following HAART De-intensification to Atazanavir/Ritonavir (ATV/r) in Adolescents With CD4 + T Cells > 350 Cells/mm3 Initiating HAART

This study proposes to evaluate a pre-DHHS guideline of HAART initiation and then de-intensification management strategy in adolescents with mild immunosuppression and compare changes in CD4% from baseline to week 48 and then during de-intensification.

NCT00491556 HIV Infections Procedure: Early Initiation of Highly Active Anti-Retroviral Therapy Procedure: Standard Care
MeSH:HIV Infections

The following genotypic mutations exclude subjects from participation in ATN 061: Major ATV mutations I50L; I84V; N88D/S, Major PI mutations including: D30N; V32I; L33I/F/V; M46I/L; I47V/A; G48V; I50V/L; I54V/L/A/M/T/S; L76V; V82A/F/T/S/L; L90M, Any major PI mutation as defined by the most current IAS-USA Drug Resistance Mutations Figures that would adversely affect a subject's future PI choices, Major RT mutations: Q151M and 69 insertion complex; Decisions regarding the selection of an NRTI backbone for subjects with NRTI resistance mutations other than those described above will be made by the site PI in consultation with the protocol chair or his designee. --- I50L --- --- I84V --- --- N88D --- --- D30N --- --- V32I --- --- L33I --- --- M46I --- --- I47V --- --- G48V --- --- I50V --- --- I54V --- --- L76V --- --- V82A --- --- L90M --- --- Q151M ---

Primary Outcomes

Measure: Difference in CD4+ T Cell Percentage Between Week 0 and Week 48

Time: Week 0 and Week 48

Measure: Difference in CD4+ T Cell Percentage Between Week 48 and Week 152

Time: 152 Weeks

Secondary Outcomes

Measure: Difference in CD4+ T Cell Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD4+ T Cell Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD4+ Naïve T Cell Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD4+ Naïve T Cell Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD4+ Termed Central Memory (TCM) Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD4+ TCM Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD4+ Effector Memory (TEM)Ro Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD4+ TEMRo Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD4+ TEMRa Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD4+ TEMRa Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8+ Naïve T-Cell Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8+ Naïve T-Cell Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8+ TCM Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8+ TCM Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8+ TEMRo Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8+ TEMRo Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8+ TEMRa Count Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8+ TEMRa Count Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 Naïve CD28 Cell Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 Naïve CD28 Cell Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 Naïve CD38 Cell Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 Naïve CD38 Cell Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 Naïve CD57 Cell Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 Naïve CD57 Cell Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 Naïve T-Cell Percentage Expressing Human Leukocyte Antigen-D Related (HLA-DR) Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 Naïve T-Cell Percentage Expressing HLA-DR Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TCM CD28 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TCM CD28 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TCM CD38 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TCM CD38 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TCM CD57 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TCM CD57 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TCM HLA-DR Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TCM HLA-DR Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRo CD28 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRo CD28 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRo CD38 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRo CD38 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRo CD57 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRo CD57 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRO HLADR Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRo HLA-DR Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRa CD28 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRa CD28 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRa CD38 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRa CD38 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRa CD57 Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRa CD57 Percentage Between Week 48 and Week 152

Time: 152 weeks

Measure: Difference in CD8 TEMRa HLA-DR Percentage Between Week 0 and Week 48

Time: 48 weeks

Measure: Difference in CD8 TEMRa HLA-DR Percentage Between Week 48 and Week 152

Time: 152 weeks

6 A Phase II, Randomized Trial of Open-Label Truvada With Darunavir/Ritonavir Versus Multiclass Therapy With Truvada, Darunavir/Ritonavir, Maraviroc and Raltegravir in Acutely HIV-1 Infected Antiretroviral-Naïve Subjects

The researchers are involved in a phase II, randomized, two-arm study, comparing the efficacy, safety, and tolerability of open-label ritonavir (RTV)-enhanced darunavir with Truvada to a 5-drug multi-class regimen including truvada, darunavir/ritonavir/maraviroc/and raltegravir on acutely HIV-1-infected, antiretroviral (ARV) drug-naïve men and women. Subjects will participate for at least 60 weeks and up to 96 weeks if in the opinion of the investigator and patient that continued therapy is in the patient's best interest. Hypotheses: - Multi-class antiretroviral therapy (ART) is superior to RTV-enhanced ATV in combination with Emtricitabine/Tenofovir DF (FTC/TDF) with respect to suppression of viral replication. - Multi-class ART is superior to RTV-enhanced ATV in combination with FTC/TDF with respect to immune reconstitution in peripheral blood and in the gastrointestinal mucosa. - Multi-class ART is equivalent to RTV-enhanced ATV in combination with FTC/TDF with respect to tolerability.

NCT00525733 HIV Infections Drug: darunavir 800 mg Drug: FTC 200 mg/TDF 300mg Drug: Maraviroc Drug: Raltegravir Drug: Ritonavir 100 mg
MeSH:Infection HIV Infections

Major resistance-associated mutations include: NRTI: K65R or inserts Q151M, M184V/I, PI: I50L/V, I84V, N88S. --- K65R --- --- Q151M ---

Primary Outcomes

Measure: The Primary Outcome of This Study is the Proportion of Patients Having Detectable HIV-1 RNA Using the Single Copy Assay After 48 Weeks of Treatment and the Study Hypothesis is That New Treatment is Better Than the Control Group.

Time: 48 weeks

7 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 ---

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 ---

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

8 A Phase 4, Single Arm, Open Label, Pilot Study of Maraviroc (Celsentri) in Combination With Raltegravir and Darunavir/Ritonavir for the Treatment of Triple Class Failure in Adult HIV-1 Infected Patients.

Phase 4, single arm, open label study designed to compare the safety and efficacy of antiviral activity and immunological effect of Maraviroc in combination with Raltegravir and Darunavir/Ritonavir for treatment of triple class failure in adult HIV-1 infected subjects. The purpose of this study is to look at the safety and efficacy of a combination of 3 new antiretroviral drugs: maraviroc, darunavir and raltegravir in patients who have multi-resistant viruses and limited treatment options. Patients will undergo treatment for 48 weeks; safety and virological efficacy will be preliminary evaluated at weeks 16 and 24.

NCT01013987 HIV-1 Adults Patients AIDS Triple Class Failure Drug: maraviroc Drug: Raltegravir Drug: Darunavir/ritonavir

Those with evidence of R5 viruses and susceptibility to darunavir in the resistance testing analysis, plus history of failure to NRTIs, NNRTIs and at least one PI, plus a genotype analysis showing evidence of resistance to NRTIs (at least 2 TAMS and/or Q151M and or 69ss), resistance to PIs (at least 2 major mutations), will start a regimen of maraviroc, raltegravir and ritonavir boosted darunavir. --- Q151M ---

Primary Outcomes

Measure: Proportion of patients with HIV RNA levels of less than 50 copies/ml in an intent to treat analysis at week 24

Time: week 24

Secondary Outcomes

Measure: Proportion of patients with HIV RNA levels of less than 50 copies/ml at week 24 and with HIV RNA levels of less than 400 copies/ ml at weeks 24 and 48.

Time: week 24 and week 48

9 Multicenter Study of Options for Second-Line Effective Combination Therapy (SELECT)

The study was conducted on people who were taking their first anti-HIV drug regimen (including an Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), a type of anti-HIV drug) but the drugs in this regimen were not doing a good job of fighting their HIV infection. The main purpose of this study was to compare two other anti-HIV drug regimens to see how well they fight HIV. The study also looked at how well participants tolerate the drug regimens and how safe they are. The study was designed to determine whether taking the combination of lopinavir/ritonavir (LPV/r) plus raltegravir (RAL) works as well as what is usually used for second-line therapy: LPV/r plus the best-available nucleoside (nucleotide) reverse transcriptase inhibitor (NRTI) combination. Testing a regimen that does not include any NRTIs was important because NRTIs may no longer work for patients who received them as part of their first treatment regimen.

NCT01352715 HIV-1 Infection Drug: Lopinavir/ritonavir Drug: Lopinavir/ritonavir Drug: Raltegravir Drug: Emtricitabine/tenofovir disoproxil fumarate Drug: Abacavir/lamivudine/zidovudine Drug: Abacavir/lamivudine Drug: Lamivudine/zidovudine Drug: Abacavir Drug: Zidovudine Drug: Lamivudine

The most significant of these mutations include M184V, thymidine analogue mutations (TAMs), Q151M complex, and K65R. --- M184V --- --- Q151M ---

The presence of K65R would result in resistance to most NRTIs (leaving only zidovudine (ZDV) and possibly abacavir (ABC) as active second-line options); the presence of multiple TAMs and/or Q151M alone or in complex with other mutations would also result in resistance to most NRTIs. --- K65R --- --- Q151M ---

Primary Outcomes

Description: The primary endpoint was time to virologic failure. Virologic failure was defined as confirmed viral load >400 copies/mL at or after week 24. The Kaplan-Meier estimate of the cumulative probability of virologic failure by week 48 was used.

Measure: Cumulative Probability of Virologic Failure by Week 48

Time: From study entry to week 48

Secondary Outcomes

Description: Change in CD4+ cell count was calculated as CD4+ cell count at week 48 minus CD4+ cell count at study entry.

Measure: Change in CD4+ Cell Count From Baseline to Week 48

Time: Study entry and week 48

Description: Mutations were defined as major IAS mutations in the IAS-USA July 2014 list. New mutations were those detected at virologic failure but not at baseline.

Measure: Number of Participants With HIV-1 Drug Resistance Mutations in Protease, Reverse Transcriptase, and Integrase in Participants With Virologic Failure at Baseline and at Time of Virologic Failure

Time: From study entry through to week 96

Description: The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs.

Measure: Number of Participants With Grade 3 or Higher Adverse Event (AE) at Least One Grade Higher Than Baseline

Time: From start of randomized treatment to off randomized treatment (up to 96 weeks)

Description: Discontinuation of randomized treatment for toxicity included participant decision to discontinue for low grade toxicity. Within class NRTI changes were not considered discontinuations.

Measure: Number of Participants Discontinuing Randomized Treatment for Toxicity

Time: From Start of Randomized Treatment to Off Randomized Treatment (up to 96 weeks)

Description: AIDS-defining events were those recognized by the Centers for Disease Control (CDC) and World Health Organization (WHO)

Measure: Number of Participants With a New AIDS-defining Events or Death

Time: From study entry throughout follow-up (up to 96 weeks)

Description: Serious non-AIDS diagnoses were based on ACTG Appendix 60 Diagnosis Codes

Measure: Number of Participants With a Targeted Serious Non-AIDS-defining Event or Death

Time: From study entry throughout follow-up (up to 96 weeks)

Description: The percentage of total study time that participants were in hospital.

Measure: Percentage of Time Spent in Hospital

Time: From study entry throughout follow-up (up to 96 weeks)

Description: Fasting was for 8 hours and the metabolic panel was drawn locally.

Measure: Changes in Fasting Total Cholesterol, High-density Lipoprotein (HDL) Cholesterol, Low-density Lipoprotein (LDL) Cholesterol, Triglycerides, and Glucose From Baseline

Time: Study entry and week 48

10 A Phase IIa, Randomized, Double-blind, Active-controlled, 12-week Study of Amdoxovir (Two Doses) Versus Tenofovir DF, in Combination With Zidovudine in HIV-1 Treatment-experienced Subjects With M184I/V Mutation in Addition to 0-2 Confirmed Thymidine Analog Mutations.

This is a double-blind Phase 2a study to test the safety and efficacy of an investigational HIV drug, amdoxovir (300 mg or 500 mg twice daily) compared with tenofovir DF 300 mg once daily in HIV-1 infected antiretroviral therapy-experienced subjects who are currently failing antiretroviral therapy. There are three treatment groups (N=45). Subjects will be randomized to receive either amdoxovir 300 mg twice daily (n=15) or amdoxovir 500 mg twice daily (n=15) or tenofovir DF 300 mg once daily (n=15); each in combination with zidovudine 300 mg twice daily. The study will assess initially amdoxovir (300 mg or 500 mg twice daily) or tenofovir DF 300 mg once daily, both in combination zidovudine 300 mg twice daily plus failing third drug, but then with lopinavir/ritonavir (400 mg/100 mg twice daily) after Week 2. Subjects who received amdoxovir (300 mg or 500 mg twice daily) and benefited from the drug may choose to enroll in the 36-week open-label study.

NCT01737359 Human Immunodeficiency Virus Infection Drug: amdoxovir 300 mg bid Drug: amdoxovir 500 mg bid Drug: tenofovir DF 300 mg qd
MeSH:Acquired Immunodeficiency Syndrome HIV Infections

- Genotypic resistance testing at screening indicating K65R, L74V, Q151M mutation. --- K65R --- --- L74V --- --- Q151M ---

Primary Outcomes

Measure: HIV-1 viral load

Time: change from baseline to Week 2

Measure: Safety and Tolerability- Incidence of adverse events and laboratory abnormalities

Time: number and frequency from baseline through Week 12

Secondary Outcomes

Measure: HIV-1 viral load

Time: change from baseline to Weeks 4, 8 and 12

Measure: Changes in Immunologic Function (CD4 cell counts)

Time: changes from baseline to Weeks 4, 8 and 12

11 A Phase 3, Two-Part Study to Evaluate the Efficacy of Tenofovir Alafenamide Versus Placebo Added to a Failing Regimen Followed by Treatment With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Plus Atazanavir in HIV-1 Positive, Antiretroviral Treatment-Experienced Adults

The primary objective of this study is to evaluate the efficacy of tenofovir alafenamide (TAF) versus placebo, each administered with the existing, failing antiretroviral (ARV) regimen. There are 2 parts to this study: Part 1 and Part 2. Part 1 consists of 2 cohorts, starting with a sentinel cohort, in which participants will be enrolled to receive open-label TAF in addition to their current failing ARV regimen. This cohort will then be followed by a randomized, double-blind, cohort to compare the addition of TAF or placebo in HIV-1 positive adults who are failing their current ARV regimen. In Part 2, all participants who complete Part 1 of the study will discontinue their failing ARV regimen and TAF or placebo for a 14-day washout period. Following the washout period, all participants who received TAF in Part 1 and have a > 0.5 log10 decline in HIV-1 RNA will receive elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen (STR) plus atazanavir (ATV) once daily for 48 weeks. Participants who received TAF who have a ≤ 0.5 log10 decline in HIV-1 RNA will be discontinued from the study and will not be eligible to continue into Part 2 of the study. All participants who received placebo in Part 1 will be eligible to participate in Part 2 regardless of their viral load change. After completion of Part 2, all participants will be eligible to continue to receive E/C/F/TAF plus ATV in the extension phase until E/C/F/TAF becomes commercially available, or until Gilead Sciences terminates development of E/C/F/TAF in the applicable country.

NCT01967940 HIV HIV Infections Acquired Immunodeficiency Syndrome Drug: TAF Drug: Placebo Drug: E/C/F/TAF Drug: Current failing ARV regimen Drug: ATV
MeSH:HIV Infections Acquired Immunodeficiency Syndrome Immunologic Deficiency Syndromes
HPO:Immunodeficiency

Key Exclusion Criteria: - A new AIDS-defining condition diagnosed within the 30 days prior to screening - Hepatitis B surface antigen (HBsAg) positive - Hepatitis C antibody positive (individuals with positive hepatitis C virus (HCV) antibody and without detectable HCV RNA are permitted to enroll) - History of integrase inhibitor use - Screening or historical genotype reports shows Q151M or T69ins or more than 3 TAMs. --- Q151M ---

Primary Outcomes

Measure: Part 1: Percentage of Participants With Plasma HIV-1 RNA Decreases From Baseline Exceeding 0.5 log10 at Day 10

Time: Day 10

Secondary Outcomes

Measure: Part 1: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Day 10

Time: Baseline; Day 10

Measure: Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 24

Time: Up to Week 24

Measure: Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Grade 3 or 4 Laboratory Abnormalities Through Week 48

Time: Up to Week 48

Measure: Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 24

Time: Up to Week 24

Measure: Part 2: Safety of E/C/F/TAF STR Plus ATV in Participants Who Switched From a Failing Regimen as Assessed by the Percentage of Participants Experiencing Any Treatment-Emergent Adverse Event Through Week 48

Time: Up to Week 48

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was 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: Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24

Time: Week 24

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was 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: Part 2: Percentage of Participants With Plasma HIV-1 RNA < 50 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48

Time: Week 48

Description: The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 24 was 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: Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 24

Time: Week 24

Description: The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 was 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: Part 2: Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL as Defined by the FDA Snapshot Analysis at Week 48

Time: Week 48

Measure: Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 24

Time: Baseline; Week 24

Measure: Part 2: Change From Baseline in Plasma log10 HIV-1 RNA (Copies/mL) at Week 48

Time: Baseline; Week 48

Measure: Part 2: Change From Baseline in CD4+ Cell Count at Week 24

Time: Baseline; Week 24

Measure: Part 2: Change From Baseline in CD4+ Cell Count at Week 48

Time: Baseline; Week 48

Measure: Part 2: Change From Baseline in CD4+ Percentage at Week 24

Time: Baseline; Week 24

Measure: Part 2: Change From Baseline in CD4+ Percentage at Week 48

Time: Baseline; Week 48

12 A Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults

The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed dose combination (FDC) plus darunavir (DRV) relative to current antiretroviral regimens (ARV) in virologically suppressed, HIV-1 positive participants with HIV-1 RNA <50 copies/mL at Week 24. This study consists of 48 weeks of open-label phase followed by an optional Extension Phase in which all the participants will receive E/C/F/TAF+DRV.

NCT01968551 HIV-1 HIV Infections Acquired Immunodeficiency Syndrome Drug: E/C/F/TAF Drug: DRV Drug: Baseline DRV- containing ARV regimen
MeSH:HIV Infections Acquired Immunodeficiency Syndrome Immunologic Deficiency Syndromes
HPO:Immunodeficiency

- Must not have Q151M, T69ins, or > 3 thymidine analogue mutations (TAMS) present on documented historic genotype report - Individuals experiencing decompensated cirrhosis - Females who are breastfeeding - Positive serum pregnancy test - Have an implanted defibrillator or pacemaker - Current alcohol or substance use that may interfere with individual's study compliance - A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. --- Q151M ---

Primary Outcomes

Description: The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a patient'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 in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 24

Time: Week 24

Secondary Outcomes

Description: The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient'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 in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 48

Time: Week 48

Measure: Change From Baseline in CD4+ Cell Count at Week 24

Time: Baseline; Week 24

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

Time: Baseline; Week 48

13 A Phase 3b Open-Label Pilot Study to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) in Virologically-Suppressed HIV-1 Infected Adult Subjects Harboring the Archived Isolated NRTI Resistance Mutation M184V/M184I

The primary objective of the study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) after switching from a stable regimen consisting of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) plus a third antiretroviral (ARV) agent in participants harboring the archived nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance mutation M184V and/or M184I in human immunodeficiency virus (HIV) -1 reverse transcriptase. This is a two part study. If the rate of virologic failure in Part 1 is deemed acceptable, once the internal data monitoring committee officially completes the interim review, the study will continue to Part 2.

NCT02616029 HIV-1 Infection Drug: E/C/F/TAF

- Proviral deoxyribonucleic acid (DNA) test must not have additional exclusion resistance mutations against PIs, NRTIs and INSTIs - Part 1: Historical genotype report must show mutation M184V and/or M184I in reverse transcriptase WITHOUT any other NRTI resistance mutation (including thymidine analogue-associated mutations [TAMs] [TAMs are: M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E/N/R], K65R, K70E, T69 insertion, and Q151M mutation complex [A62V, V75I, F77L, F116Y, Q151M]) - Part 2 (after the interim efficacy review): Historical genotype report must show M184V and/or M184I in reverse transcriptase WITH or WITHOUT 1 or 2 TAMs. --- M184V --- --- M184I --- --- M41L --- --- D67N --- --- K70R --- --- L210W --- --- T215Y --- --- K219Q --- --- K65R --- --- K70E --- --- Q151M ---

- Proviral deoxyribonucleic acid (DNA) test must not have additional exclusion resistance mutations against PIs, NRTIs and INSTIs - Part 1: Historical genotype report must show mutation M184V and/or M184I in reverse transcriptase WITHOUT any other NRTI resistance mutation (including thymidine analogue-associated mutations [TAMs] [TAMs are: M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E/N/R], K65R, K70E, T69 insertion, and Q151M mutation complex [A62V, V75I, F77L, F116Y, Q151M]) - Part 2 (after the interim efficacy review): Historical genotype report must show M184V and/or M184I in reverse transcriptase WITH or WITHOUT 1 or 2 TAMs. --- M184V --- --- M184I --- --- M41L --- --- D67N --- --- K70R --- --- L210W --- --- T215Y --- --- K219Q --- --- K65R --- --- K70E --- --- Q151M --- --- A62V --- --- V75I --- --- F77L --- --- F116Y --- --- Q151M ---

Evidence of K65R, K70E, T69 insertion and/or Q151M mutation complex will not be eligible - Currently receiving an ARV regimen consisting of FTC/TDF or ABC/3TC in combination with one third ARV agent for ≥ 6 consecutive months preceding the screening visit - Documented plasma HIV-1 ribonucleic acid (RNA) levels < 50 copies/mL for ≥ 6 months preceding the screening visit - Plasma HIV-1 RNA levels < 50 copies/mL at screening visit - Estimated glomerular filtration rate (GFR) ≥ 30 mL/min according to the Cockcroft-Gault formula for creatinine clearance - A female individual is eligible to enter the study if it is confirmed that she is: - not pregnant - of non-childbearing potential - stopped menstruating for ≥ 12 months - of childbearing potential and agrees to utilize the protocol-specified method of contraception or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following discontinuation of study drugs - Male individuals must agree to use the protocol-specified method(s) of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from screening throughout the study period and for 30 days following the last study drug dose - Male individuals must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose Key Exclusion Criteria: - Individuals will have no evidence of previous virologic failure on a PI/r or INSTI-based regimen (with or without resistance to either class of ARV). --- K65R --- --- K70E --- --- Q151M ---

Primary Outcomes

Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 12 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.

Measure: Percentage of Participants With Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) < 50 Copies/mL at Week 12 as Defined by Pure Virologic Response (PVR)

Time: Week 12

Secondary Outcomes

Description: Development of new resistance mutations was assessed in participants who developed virologic failure, defined as 2 consecutive HIV-1 RNA result ≥ 50 copies/mL at any point in the study or with HIV-1 RNA ≥ 50 copies/mL at last visit.

Measure: Percentage of Participants With Emergence of New Mutations in HIV-1 Reverse Transcriptase and Integrase

Time: Day 1 up to 48 weeks

Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 24 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using PVR

Time: Week 24

Description: The percentage of participants with PVR for HIV-1 RNA cutoff at 50 copies/mL at Week 48 was summarized. PVR was the percentage of participants who did not have a confirmed virologic rebound. Virologic rebound was defined as 2 consecutive HIV-1 RNA values ≥ 50 copies/mL or the last available HIV-1 RNA value ≥ 50 copies/mL during the study followed by premature discontinuation from the study.

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

Time: Week 48

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was also 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. Week 12 window was between Day 71 and 98 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the FDA Snapshot Analysis

Time: Week 12

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was also 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. Week 24 window was between Day 141 and 210 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the FDA Snapshot Analysis

Time: Week 24

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was also 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. Week 12 window was between Day 295 and 378 (inclusive).

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

Time: Week 48

Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 12 was also 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. Week 12 window was between Day 71 and 98 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 12 Using the FDA Snapshot Analysis

Time: Week 12

Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 24 was also 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. Week 24 window was between Day 141 and 210 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 24 Using the FDA Snapshot Analysis

Time: Week 24

Description: The percentage of participants with HIV-1 RNA < 20 copies/mL at Week 48 was also 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. Week 12 window was between Day 295 and 378 (inclusive).

Measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Week 48 Using the FDA Snapshot Analysis

Time: Week 48

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the Missing = Failure (M = F) Approach

Time: Week 12

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the M = F Approach

Time: Week 24

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the M = F approach. In this approach, all missing data was treated as HIV-1 RNA ≥ 50 copies/mL.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = F Approach

Time: Week 48

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 12 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 12 Using the Missing = Excluded (M = E) Approach

Time: Week 12

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 Using the M = E Approach

Time: Week 24

Description: The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was also analyzed using the M = E approach. In this approach, all missing data was excluded in the computation of the proportions.

Measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach

Time: Week 48

Measure: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 12

Time: Baseline (Day 1); Week 12

Measure: Change From Baseline in CD4+ Cell Count at Week 24

Time: Baseline (Day 1); Week 24

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

Time: Baseline (Day 1); Week 48

Measure: Change From Baseline in CD4 Percentage (%) at Week 12

Time: Baseline (Day 1); Week 12

Measure: Change From Baseline in CD4 % at Week 24

Time: Baseline (Day 1); Week 24

Measure: Change From Baseline in CD4 % at Week 48

Time: Baseline (Day 1); Week 48

14 A Phase 4, Randomized, Open Label, Controlled Study of Boosted Darunavir and Lamivudine Versus Boosted Darunavir and Emtricitabine/Tenofovir or Lamivudine/Tenofovir in Naïve HIV-1 Infected Subjects

The purpose of this study is to compare the safety and efficacy of a combination of a QD regimen consisting on ritonavir boosted darunavir (FDC) and lamivudine versus ritonavir boosted darunavir (FDC) plus co-formulated tenofovir and emtricitabine or co-formulated tenofovir/lamivudine in naïve HIV-1 infected patients. Subjects will be ARV-naïve HIV-1-infected patients eligible to start ARV therapy according to current guidelines.Subjects will be adults ≥ 18 years of age who meet all of the inclusion criteria and none of the exclusion criteria.

NCT02770508 HIV-1 Infection Drug: darunavir/ritonavir Drug: Lamivudine Drug: emtricitabine-tenofovir(FTC/TDF)

- Any of the following mutations will be considered resistance to 3TC or FTC : M184V/I and /or K65R and / or Q151M. --- M184V --- --- K65R --- --- Q151M ---

Primary Outcomes

Description: The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) <50 c/mL at Week 48 will be assessed using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm. This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, Otherwise, virologic success or failure will be determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks).

Measure: Percentage of patients with HIV-1 RNA levels of less than 50 copies/mL at week 48

Time: 48 weeks

Secondary Outcomes

Description: The percentage of participants with Plasma Human Immunodeficiency Virus-1 (HIV-1) <400 c/mL at Week 24 will be assessed using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm.

Measure: Percentage of patients with HIV-1 RNA <400 copies/mL at week 24

Time: 24 weeks

Description: An genotiping test will be made at time to virological failure to detect mutation across reverse transcriptase (RT), and Protease (PRO). Protocol defined virological failure was defined as confirmed plasma HIV-1 RNA levels >=400 copies/mL on or after Week 24 or confirmed plasma HIV-1 RNA levels >=50 copies/mL at week 48

Measure: Number and type of resistance mutations in case of virologic failure

Time: from week 24 to week 48

Description: Change from Baseline in CD4+ cell counts will be assessed at Weeks 24 and 48.

Measure: CD4+ lymphocyte count and change between baseline (defined as the average between screening and baseline visit values) and weeks 24 and 48

Time: week 24 and 48

Description: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment

Measure: Frequency, type and severity of adverse events and laboratory abnormalities.

Time: week 24 and 48

Description: Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CDC CAT A at Baseline (BS) to a CDC CAT C event (EV); CDC CAT B at BS to a CDC CAT C EV; CDC CAT C at BS to a new CDC CAT C EV; or CDC CAT A, B, or C at BS to death.

Measure: Clinical disease progression (CDP)

Time: week 24 and 48

Description: The evaluation of quality of life will be done through two validated instruments: the Medical Outcomes Study HIV Health Survey ( MOS - HIV) and EuroQol 5D (EQ - 5D ) . Both instruments will be administered to patients at baseline , week 24 and week 48 .

Measure: Changes in quality of life

Time: baseline, week 24 and week 48

15 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 HIV-1-infection Weight Gain 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 --- --- G190E --- --- P225H --- --- F227C --- --- F227L --- --- F227R --- --- M230L --- --- L234I --- --- K65R --- --- K65E --- --- K65N --- --- T69S --- --- K70E --- --- L74V --- --- Y115F --- --- Q151M ---

Primary Outcomes

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

Measure: Change in energy balance

Time: 24 weeks


HPO Nodes


HP:0002721: Immunodeficiency
Genes 268
PIK3CA CCDC47 CTBP1 ATRX NHEJ1 BLNK CHD1 CD81 NOP10 IKBKB CD79A TNFRSF13C CD19 AICDA LIG4 CD19 IRF2BP2 LAMTOR2 IFNGR1 UNC119 IGHM TTC7A CD81 PNP SPATA5 RAG2 PKP1 WRAP53 ADA2 TTC37 FGFRL1 CLCA4 TERT RAG1 HYOU1 LAT TYK2 LRBA TTC7A NFE2L2 CD19 DCTN4 RREB1 CD40LG FRAS1 IKBKG TNFRSF13B CFTR RAG1 IRAK4 MAN2B1 CTLA4 JAK3 SHANK3 AGL IL21 ICOS PRKDC TNFRSF13C XRCC4 LIG4 CARD9 BSCL2 TBCE CTPS1 IL7R ANTXR2 MAN2B1 HELLS IL21R MALT1 CD3G LAMTOR2 AP3D1 CD40 ARVCF MBTPS2 ACP5 PTPRC NFKB2 TFRC MS4A1 MAPK1 MTHFD1 LYST ADA POLE RAG2 XIAP SDHC DNMT3B UNG BCL11B DOCK2 ORAI1 RTEL1 IL12RB1 TLR3 FOS AK2 IL2RG TRAF3 CTLA4 DCLRE1C SIN3A SLC46A1 LRRC8A AGPAT2 TINF2 DCLRE1C IRF7 GP1BB TGFB1 UFD1 PPARG LETM1 CAVIN1 ADA ICOS SP110 CD247 IL2RG IRAK4 RAC2 ICOS MMUT TICAM1 KLLN PIK3R1 WIPF1 NFKB1 RBCK1 CORO1A IRF8 STAT1 XRCC4 MEIS2 EPG5 RTEL1 ZBTB24 IKZF1 NSD2 XIAP EXTL3 NCF1 STIM1 FOXN1 MS4A1 GATA2 COG6 CRKL ISG15 COMT RAG1 NPM1 ATM WAS HBB RNF168 RMRP SKIV2L CDCA7 JMJD1C STAT1 CHD1 FOXN1 PRPS1 RAB27A CDC42 UROS BCL10 SKIV2L DKC1 TNFRSF13C DNMT3B FCGR3A HIRA DKC1 ACTB BCR TNFRSF4 ZBTB24 CDH23 SH2D1A CPLX1 CYBA PGM3 CDC42 SEC23B STK4 TBX1 CD3E CD79B CHD7 POLE ACD IGLL1 TERC IFNGR2 TNFRSF13B CD28 UNC93B1 STX1A EPG5 AKT1 TBK1 SMARCAL1 TERT CR2 IRF8 RMRP IL2RG IL12B IL2RB NFKB1 NCF2 RAG2 WHCR PARN RTEL1 SIK3 SDHB LMNB2 PIK3CD CARD11 FCN3 CAV1 TBX1 TCF3 CYBB PIK3R1 CR2 USF3 PTEN MYC TNFSF12 AK2 MAGT1 CR2 IL2RA LCK RNF168 CD3D NHP2 IKBKG SEC24C PARN NFKB2 IL7R TNFSF12 BTK LYST CUL4B USB1 BUB1B PRKCD CTC1 SPATA5 DKC1 STAT1 GATA1 TINF2 USP8 RAG1 PGM3 TNFRSF1B SDHD MYD88
SNP 0
HP:0004324: Increased body weight
Genes 529
SHOX HACE1 THOC2 LIMK1 FMR1 SOX3 PHF6 CLCN4 IFT172 TNFSF4 PDX1 KCNAB2 AGRP GNAS ADCY3 HLA-DRB1 AFF4 REEP6 PRPF6 KLF11 KIAA1549 ARL6 DNM2 ELN MKS1 PWAR1 IFT27 SDC3 LIPE SYNE2 RAB39B FGF8 ARHGEF6 RDH12 ZNF408 BRAF SH2B1 BPTF HLA-DQB1 ANOS1 LMNA TRIM32 ARX AKT1 KIF7 TRIP12 FIBP SLC7A7 IL1RAPL1 SHANK3 INS EGF CFI RAI1 SYNE1 GNAS ATP6AP2 MTOR XRCC4 SLC7A14 GNAS HDAC8 BBS2 HSD11B1 MC4R AGBL5 ANK3 KMT2D ACADVL BBS4 MEGF8 CYP7A1 RAD21 PIGN ARVCF BEST1 RPS6KA3 ZNF365 ADRB3 CRX MID2 ATRX NDN UCP3 IQSEC2 SKI RBP3 CNGB1 RAB23 ZNF513 SLC25A4 FLRT3 FIBP KISS1R CCDC141 IFT140 TSPAN7 CCDC141 RAI1 ARMC5 TRAF3IP1 TP53 LZTFL1 SUFU OFD1 MAGEL2 SMC1A AKT2 GNAS ARL6 GTF2IRD1 UFD1 TRIM32 CDHR1 NF2 MEGF8 SNORD115-1 WT1 HACE1 SH2B1 CNGA1 DHDDS RFC2 PSMD12 SMO KIZ HNF1A NTRK2 BBS10 DCC PRPF8 FOXP1 EP300 SOX10 POU3F4 DIS3L2 BAP1 TMEM43 NEK2 DEAF1 GNAS-AS1 BBS9 SIN3A SNRPN MAK FGFR1 PHF6 CLIP2 BBS2 COMT BBS2 HESX1 MTOR HESX1 GNAS PRKACA JMJD1C TCF20 MCM3AP NEUROD1 LZTFL1 ARL6 CFH ABCA4 C8ORF37 GHR TMEM67 USP8 AP4B1 UCP2 HIRA LEP IQSEC2 CERKL NRL PAX6 TBX1 SRY H6PD CREBBP PRKAR1A PROM1 ZNF41 PCSK1 RYR1 PCSK1 EHMT1 IMPDH1 CNNM2 RNPC3 C8ORF37 ZNF711 LEPR TTC8 ALMS1 PRCD PROKR2 ELN PNPLA6 MTMR14 PAX4 MKKS GATA4 SYP EDNRB VPS13B FGF17 PRPF4 HNF1A CA4 GDI1 TUB POMC AIP TTC8 ENPP1 KIDINS220 SLC9A7 CEP164 NSD1 NR2E3 TBX1 HNF4A PWRN1 MC3R KIDINS220 USP7 KMT2A BDNF MTTP PCARE ARL6 POMC SUFU PIGT P2RY11 IQSEC2 BBS10 RAB23 KCNJ18 PDE4D BBS9 HDAC4 TUB XYLT1 SEC24C PDSS1 HGSNAT EIF2S3 IGF1R MAGEL2 IPW FTO GCK SPRY4 KCNJ11 PRMT7 ARHGEF18 DYRK1B XYLT1 RP1 GNAS CLRN1 AHR MED12 HDAC8 CTSH BRAF TTC8 ABCC9 PNKP IFT172 FGFR1 SIM1 MKKS FTSJ1 MAPK8IP3 ALB IFT74 ALMS1 GUCA1B UPF3B ATRX PDE6G CTNNB1 CCDC28B HERC1 SETD2 SLC10A7 APOE NIPBL BBS7 RAI1 GLI3 HCFC1 PRDM16 TOPORS WDR11 BBS5 IDH3B PIK3CA SCAPER MYF6 ARL2BP SPG11 IGSF1 CXORF56 ADRB2 HS6ST1 RREB1 LAS1L PDE6B AP4M1 BLK UBE2A IL17RD ADNP TBX3 NPAP1 P4HTM TMCO1 EIF2S3 PRPF3 CARTPT SMC3 POMC SPATA7 SH3KBP1 MECP2 CYP19A1 BBS12 MKS1 NKAP HDAC8 RERE PRKAR1A TAF1 UBE3A MLXIPL KCNJ11 KCNJ11 INPP5E HCRT IGF1 ABCC8 RPGR HNF4A APC2 CNKSR2 PIGA BLK BIN1 PRMT7 MC4R PPARG RPS6KA3 HUWE1 BAZ1B PDGFB PROKR2 NIN AHI1 RBMX SOX2 SAG MECP2 TRAF7 WDPCP HERC2 ABCC8 GP1BB TRAPPC9 BBS12 CEP290 TRIP4 ADNP MKRN3-AS1 PTCHD1 ACSL4 CUL4B BAP1 NR0B2 PROK2 TERT PCNT PCNT EYS WT1 FGFR3 IFT27 RGR GTF2I ZNF711 SDCCAG8 EMD LAS1L CACNA1S GNAS DHX38 IDH3A USP27X DYNC2I2 PIGT MEN1 ATP7B THOC2 PDE4D TACR3 LEPR RHO POGZ MRAP2 EXOC6B BBS5 ZBTB20 PIGL FOXP1 AP4S1 RP9 PTCH1 BBS7 SH2B1 KLHL7 EHMT1 DNMT3A ARMC5 RLBP1 ALG13 AGTR2 HNF4A MYT1L VPS13B CDH23 PAX6 PAK3 SMARCB1 THRA LEP BBS4 ARL13B DUSP6 MKRN3 TRAPPC9 AFF4 SDCCAG8 TBX1 GHRL BBS1 STX16 BBIP1 USH2A MOG LMNA PROK2 OFD1 SIM1 FLII RP2 SETD5 MOG FRMPD4 DPYD IFT172 APPL1 ARNT2 SNORD116-1 NSMF BBS1 DLG3 AP4E1 FAM161A RPE65 PDE4D PRPH2 ROM1 TBL2 OTX2 FHL1 RNF135 ERMARD C8ORF37 NPHP1 CEP19 DMD SEMA4A HELLPAR ARL3 PHIP CEL MAN1B1 LRAT CANT1 GABRD TULP1 SNRNP200 IFT88 MTFMT AKT2 FSCN2 CEP290 MERTK SEMA3A BBIP1 PDE11A CHD7 IMPG2 POMGNT1 SMARCE1 CD46 ABCC8 SMAD4 IFT172 MAN1B1 CUL4B USP9X PRPF31 PTEN KDM6A IGFALS WNT4 SETD2 GNAS TBX3 PDE6A FEZF1 USP8 CRB1 ZNF81 GABRA3
Protein Mutations 1
G551D