There are 63 clinical trials

Clinical Trials

1 A Phase II, Randomized Study of the Antiviral Activity and Resistance Interactions of Lamivudine (3TC) in Combination With Zidovudine (AZT), Stavudine (d4T), or Didanosine (ddI) Versus Monotherapy With ddI or d4T in HIV-Infected Individuals With 200 - 600 CD4+ Cells/mm3 and No Previous Nucleoside Experience

To evaluate the efficacy, safety, and pharmacokinetics of lamivudine (3TC) combined with zidovudine (AZT), stavudine (d4T), or didanosine (ddI) in comparison with d4T or ddI monotherapy in HIV-infected patients with no prior nucleoside therapy. 3TC may be uniquely effective in combination with AZT due to the interaction of AZT and 3TC resistance mutations. One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. This benefit of 3TC may not extend to combination therapy with other nucleoside analogs.

NCT00000838 HIV Infections Drug: Lamivudine Drug: Stavudine Drug: Zidovudine Drug: Didanosine

MeSH:HIV Infections

One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. --- M184V ---

2 A Phase 2 Trial of 4 Weeks of ACH-126,443 in Comparison With Continued Lamivudine in Stable Triple Antiretroviral Combination Therapy in HIV-Infected Subjects With Modestly Detectable Viral Load

To determine safety and efficacy of ACH-126,443 on the treatment of adults with HIV infection who have modestly detectable viral load while on stable triple combination antiretroviral therapy including 3TC.

NCT00040157 HIV Infections Drug: ACH126-443 (Beta-L-Fd4C)

MeSH:Infection HIV Infections Acquired Immunodeficiency Syndrome

Inclusion Criteria: - Adults ≥18 years of age - Receiving a stable triple combination antiretroviral regimen including 3TC, one other NRTI and either an NNRTI or a protease inhibitor for at least 4 months (16 weeks) - Demonstration of initial viral suppression and subsequent rebound to be defined as an initial virological drop of at least 0.5 Logs on a 3TC-containing regimen - Plasma HIV RNA level > 1000 and < 30,000 copies/mL on two occasions - Genotypically documented M184V variant of HIV RT - Clinically stable HIV status with no AIDS-defining events - CD4 > 200 cells/mm3 - Basic hematologic and chemistry parameters within acceptable limits (defined in protocol) - All women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity of 25 IU/L of b-HCG) within 72 hours prior to the start of study medication - No active opportunistic infection requiring treatment - Subject must be able to provide written informed consent - Baseline laboratory values measured within 28 days of initiating study drug as follows: - HGB≥9.0g/dl or HCT≥27% (in the absence of blood transfusions or erythropoietin treatment in the preceding two weeks - Absolute neutrophil count≥1000 cells/mm(^3) (in the absence of on-going G-CSF therapy - Platelet count ≥75,000/mm(^3) - AST <7.0 times the upper limit of normal - ALT ,7.0 times the upper limit of normal - Serum creatinine <1.1 times the upper limit of normal Exclusion Criteria - Evidence of active HBV infection as demonstrated by HBsAg positivity - Hepatitis C co-infection - Concurrent systemic antiviral treatment - Previous therapy with agents with significant systemic myelosuppressive or cytotoxic potential within 3 months of study start or the expected need for such therapy at study start. --- M184V ---

- Use of any other drug or substance with anti-HBV activity Inclusion Criteria: - Adults ≥18 years of age - Receiving a stable triple combination antiretroviral regimen including 3TC, one other NRTI and either an NNRTI or a protease inhibitor for at least 4 months (16 weeks) - Demonstration of initial viral suppression and subsequent rebound to be defined as an initial virological drop of at least 0.5 Logs on a 3TC-containing regimen - Plasma HIV RNA level > 1000 and < 30,000 copies/mL on two occasions - Genotypically documented M184V variant of HIV RT - Clinically stable HIV status with no AIDS-defining events - CD4 > 200 cells/mm3 - Basic hematologic and chemistry parameters within acceptable limits (defined in protocol) - All women of child bearing potential must have a negative serum or urine pregnancy test (minimum sensitivity of 25 IU/L of b-HCG) within 72 hours prior to the start of study medication - No active opportunistic infection requiring treatment - Subject must be able to provide written informed consent - Baseline laboratory values measured within 28 days of initiating study drug as follows: - HGB≥9.0g/dl or HCT≥27% (in the absence of blood transfusions or erythropoietin treatment in the preceding two weeks - Absolute neutrophil count≥1000 cells/mm(^3) (in the absence of on-going G-CSF therapy - Platelet count ≥75,000/mm(^3) - AST <7.0 times the upper limit of normal - ALT ,7.0 times the upper limit of normal - Serum creatinine <1.1 times the upper limit of normal Exclusion Criteria - Evidence of active HBV infection as demonstrated by HBsAg positivity - Hepatitis C co-infection - Concurrent systemic antiviral treatment - Previous therapy with agents with significant systemic myelosuppressive or cytotoxic potential within 3 months of study start or the expected need for such therapy at study start. --- M184V ---

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

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

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

Following mutations associated with NRTIs were summarized at time of failure: Any zidovudine/lamivudine (Zid/Lam), Any thymidine analogue-associated mutation (TAM), methionine (M) to valine/isoleucine (V/I) substitution at residue (r) 184 (M184V/I), lysine (K) to arginine (R) substitution at residue 65 (K65R) and any other NRTI mutations.. Number of Participants With Efavirenz Associated Mutations at Time of Treatment Failure Through Week 48 and 96. --- M184V ---

4 A Phase 4, Single-Arm Study to Evaluate the Safety, Antiviral Activity and Pharmacokinetics of Tenofovir Disoproxil Fumarate in Combination With Emtricitabine in HIV-1 Infected Patients Experiencing Various Degrees of Renal Impairment

The purpose of this study is to provide long-term clinical safety and efficacy data for tenofovir disoproxil fumarate and emtricitabine in HIV-infected patients experiencing various degrees of renal impairment.

NCT00106379 HIV Infections Drug: Truvada (tenofovir DF + emtricitabine) Drug: Emtriva (emtricitabine) Drug: Viread (tenofovir DF)

MeSH:HIV Infections

- Women of childbearing potential who are unwilling to use an effective contraceptive method during the study - Contraindications to tenofovir DF, emtricitabine or efavirenz - Undergoing treatment for tuberculosis - Using atazanavir - Prior history of mutation M184V, K65R or T69 insertion - Z-score on pre-baseline DEXA scan less than -2.5 - The following laboratory values within 30 days prior to study entry: *absolute neutrophil count (ANC) less than 750/mm3, *hemoglobin less than 9.0 g/dL, *platelet count less than 50,000/mm3, *AST (SGOT) or ALT (SGPT) less than 5 x ULN and *CD4 cell count less than 100/mm3. --- M184V ---

5 A Phase II, Open Label, Single Arm Study of the 48-Week Virologic and Immunologic Response to Lopinavir/Ritonavir (Kaletra) as a Single Agent in a Cohort of HIV Positive Adult Patients

Expected Enrollment: 40 patients Study Start Date: June 2005 Study Objectives: - To conduct a pilot study to assess the safety, tolerability, and antiviral activity of Kaletra 400/100 mg taken twice a day (bid) in antiretroviral (ARV)-naïve HIV-infected patients at Week 48 Primary Objectives: - To determine the proportion of patients with HIV RNA <400 copies/mL at weeks 24 and 48 - To determine the proportion of patients with HIV RNA < 50 at weeks 24 and 48 - To elucidate the specific adverse event (AE) profile of Kaletra single agent therapy Secondary Objectives: - To assess the proportion of patients below the limit of quantification (LOQ) at each visit. Patients will be observed at baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 and 48. - To determine the time to HIV RNA reaching <400 and <50 copies/mL - To determine the time to virologic failure - To assess change from baseline at each visit for HIV RNA and CD4 count at weeks 4, 8, 12, 24 and 48. - To assess changes in genotype from baseline to time of confirmed virologic failure (2 consecutive HIV RNA measurements >400 copies/mL after suppressing to <400 copies/mL) or at time of treatment intensification. - To characterize changes in lipid and triglyceride concentrations over time and the effect of treatment with appropriate drugs (fibrate or statin, if necessary) on these elevations. - To evaluate the safety and tolerability of subjects through 48 weeks of drug exposure. - To describe virologic response following intensification in Kaletra single agent virologic failures

NCT00116636 HIV Infections Drug: Kaletra

MeSH:HIV Infections HIV Seropositivity

- Patient has an M184V mutation in reverse transcriptase, or mutations at 10, 20, 32, 46, 47, 48, 50, 54, 71, 73, 82, 84, or 90; - K65R mutation or 2 or more TAMs at baseline - History of active substance abuse, excluding cannabis, or psychiatric illness that, in the opinion of the investigator, would preclude compliance with protocol, dosing schedule and assessments. --- M184V ---

6 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

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. --- M184V ---

- Subjects who have the M184V HIV mutation, as determined by the FDA-approved Bayer assay, TRUGENE® HIV-1 Genotyping Kit and the OpenGene® DNA Sequencing System. --- M184V ---

7 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 --- --- M184V ---

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 --- --- M184V ---

8 A Phase II, Randomised, Double-blind, Dose-ranging Study of AVX754 Versus Lamivudine in Treatment-experienced HIV-1 Infected Patients With the M184V Mutation in Reverse Transcriptase

The study will measure how safe and effective AVX754 (a new drug for the treatment of HIV) is in treating HIV-1 infected people who have failed treatment with lamivudine.

NCT00126880 HIV Infections Drug: AVX754 Drug: 3TC

MeSH:HIV Infections

A Phase II, Randomised, Double-blind, Dose-ranging Study of AVX754 Versus Lamivudine in Treatment-experienced HIV-1 Infected Patients With the M184V Mutation in Reverse Transcriptase. --- M184V ---

Inclusion Criteria: - HIV-1 infected - M184V mutation in reverse transcriptase - Currently taking lamivudine - Viral load >2000 copies/ml Exclusion Criteria: - Hepatitis B surface antigen positive - Pregnant or breastfeeding females - Hepatitis C RNA positive and requiring treatment Inclusion Criteria: - HIV-1 infected - M184V mutation in reverse transcriptase - Currently taking lamivudine - Viral load >2000 copies/ml Exclusion Criteria: - Hepatitis B surface antigen positive - Pregnant or breastfeeding females - Hepatitis C RNA positive and requiring treatment HIV Infections HIV Infections Lamivudine or emtricitabine are commonly used in combination with other drugs for first-line treatment of HIV infection. --- M184V ---

Inclusion Criteria: - HIV-1 infected - M184V mutation in reverse transcriptase - Currently taking lamivudine - Viral load >2000 copies/ml Exclusion Criteria: - Hepatitis B surface antigen positive - Pregnant or breastfeeding females - Hepatitis C RNA positive and requiring treatment Inclusion Criteria: - HIV-1 infected - M184V mutation in reverse transcriptase - Currently taking lamivudine - Viral load >2000 copies/ml Exclusion Criteria: - Hepatitis B surface antigen positive - Pregnant or breastfeeding females - Hepatitis C RNA positive and requiring treatment HIV Infections HIV Infections Lamivudine or emtricitabine are commonly used in combination with other drugs for first-line treatment of HIV infection. --- M184V --- --- M184V ---

Resistance is associated with characteristic mutations, which for lamivudine is the M184V mutation. --- M184V ---

9 The Role of 3TC/FTC in Partially Suppressive Antiretroviral Regimens: The Switch Study

In this study the researchers will be enrolling patients who are failing their current antiretroviral regimen who also have resistance to 3TC or FTC. Patients will have their current antiretroviral regimen changed based on resistance testing and also be randomly assigned to either include, or not include 3TC/FTC in this new regimen. The purpose of the research is to investigate whether the change in therapy results in a decrease in the amount of virus particles and an increase in the CD4 cell count. In addition the researchers are investigating the relationship between the existence of resistance and the rate of decrease in viral load, and also to determine if continuing 3TC/FTC (despite being resistant to the medications) has any effect on the rate of decrease of viral load, or effect on CD4 counts.

NCT00152061 HIV Infections Drug: 3TC and FTC

MeSH:HIV Infections

To evaluate the impact of continued versus discontinued 3TC/FTC on the prevalence, frequency and dynamics of the M184V/I amino acid substitution over 24 weeks.. null. --- M184V ---

Inclusion Criteria: - HIV-1 seropositive patients >= 18 years of age - Willingness and ability to understand and sign a written informed consent and comply with the protocol procedure - Prior treatment with nucleoside reverse transcriptase inhibitors (NRTI's), non-nucleoside reverse transcriptase inhibitors (NNRTI's) and protease inhibitor (PI)-containing regimens - On a stable PI and 3TC or FTC -containing regimen for >= 2 months - Plasma HIV-1 RNA >5000 copies/ml - CD4 >100 - Documented M184V or I on genotype within 3 months of study entry - At least 3 PI-associated resistance mutations on genotype within 3 months of study entry, (including known resistance mutations at codons 10, 30, 46, 50, 54, 71, 82, 84, and 90) Exclusion Criteria: - In the opinion of the investigator a patient that is either unwilling or unable to be adherent to antiretroviral drugs - Requirement for concomitant treatment with medicines that interfere with the therapy prescribed in the study - Patients who have never taken 3TC or FTC, or with no prior documentation of the M184V mutation - Active hepatitis B infection - Vaccination within 2 weeks of entering the study - An acute opportunistic illness within 4 weeks of entering the study; chronic infections will not be excluded - Use of immunomodulatory medications such as IL-2 - Planned use of enfuvirtide, (T20) in salvage regimen, (in T20 naïve subjects) Inclusion Criteria: - HIV-1 seropositive patients >= 18 years of age - Willingness and ability to understand and sign a written informed consent and comply with the protocol procedure - Prior treatment with nucleoside reverse transcriptase inhibitors (NRTI's), non-nucleoside reverse transcriptase inhibitors (NNRTI's) and protease inhibitor (PI)-containing regimens - On a stable PI and 3TC or FTC -containing regimen for >= 2 months - Plasma HIV-1 RNA >5000 copies/ml - CD4 >100 - Documented M184V or I on genotype within 3 months of study entry - At least 3 PI-associated resistance mutations on genotype within 3 months of study entry, (including known resistance mutations at codons 10, 30, 46, 50, 54, 71, 82, 84, and 90) Exclusion Criteria: - In the opinion of the investigator a patient that is either unwilling or unable to be adherent to antiretroviral drugs - Requirement for concomitant treatment with medicines that interfere with the therapy prescribed in the study - Patients who have never taken 3TC or FTC, or with no prior documentation of the M184V mutation - Active hepatitis B infection - Vaccination within 2 weeks of entering the study - An acute opportunistic illness within 4 weeks of entering the study; chronic infections will not be excluded - Use of immunomodulatory medications such as IL-2 - Planned use of enfuvirtide, (T20) in salvage regimen, (in T20 naïve subjects) HIV Infections HIV Infections In this randomized, open-label, controlled trial, HIV-infected patients who are failing 3TC/FTC-containing highly active antiretroviral therapy, (HAART), will be offered individual treatment selection based on best clinical judgment and genotypic HIV-RNA resistance analysis. --- M184V ---

Inclusion Criteria: - HIV-1 seropositive patients >= 18 years of age - Willingness and ability to understand and sign a written informed consent and comply with the protocol procedure - Prior treatment with nucleoside reverse transcriptase inhibitors (NRTI's), non-nucleoside reverse transcriptase inhibitors (NNRTI's) and protease inhibitor (PI)-containing regimens - On a stable PI and 3TC or FTC -containing regimen for >= 2 months - Plasma HIV-1 RNA >5000 copies/ml - CD4 >100 - Documented M184V or I on genotype within 3 months of study entry - At least 3 PI-associated resistance mutations on genotype within 3 months of study entry, (including known resistance mutations at codons 10, 30, 46, 50, 54, 71, 82, 84, and 90) Exclusion Criteria: - In the opinion of the investigator a patient that is either unwilling or unable to be adherent to antiretroviral drugs - Requirement for concomitant treatment with medicines that interfere with the therapy prescribed in the study - Patients who have never taken 3TC or FTC, or with no prior documentation of the M184V mutation - Active hepatitis B infection - Vaccination within 2 weeks of entering the study - An acute opportunistic illness within 4 weeks of entering the study; chronic infections will not be excluded - Use of immunomodulatory medications such as IL-2 - Planned use of enfuvirtide, (T20) in salvage regimen, (in T20 naïve subjects) Inclusion Criteria: - HIV-1 seropositive patients >= 18 years of age - Willingness and ability to understand and sign a written informed consent and comply with the protocol procedure - Prior treatment with nucleoside reverse transcriptase inhibitors (NRTI's), non-nucleoside reverse transcriptase inhibitors (NNRTI's) and protease inhibitor (PI)-containing regimens - On a stable PI and 3TC or FTC -containing regimen for >= 2 months - Plasma HIV-1 RNA >5000 copies/ml - CD4 >100 - Documented M184V or I on genotype within 3 months of study entry - At least 3 PI-associated resistance mutations on genotype within 3 months of study entry, (including known resistance mutations at codons 10, 30, 46, 50, 54, 71, 82, 84, and 90) Exclusion Criteria: - In the opinion of the investigator a patient that is either unwilling or unable to be adherent to antiretroviral drugs - Requirement for concomitant treatment with medicines that interfere with the therapy prescribed in the study - Patients who have never taken 3TC or FTC, or with no prior documentation of the M184V mutation - Active hepatitis B infection - Vaccination within 2 weeks of entering the study - An acute opportunistic illness within 4 weeks of entering the study; chronic infections will not be excluded - Use of immunomodulatory medications such as IL-2 - Planned use of enfuvirtide, (T20) in salvage regimen, (in T20 naïve subjects) HIV Infections HIV Infections In this randomized, open-label, controlled trial, HIV-infected patients who are failing 3TC/FTC-containing highly active antiretroviral therapy, (HAART), will be offered individual treatment selection based on best clinical judgment and genotypic HIV-RNA resistance analysis. --- M184V --- --- M184V ---

Inclusion Criteria: - HIV-1 seropositive patients >= 18 years of age - Willingness and ability to understand and sign a written informed consent and comply with the protocol procedure - Prior treatment with nucleoside reverse transcriptase inhibitors (NRTI's), non-nucleoside reverse transcriptase inhibitors (NNRTI's) and protease inhibitor (PI)-containing regimens - On a stable PI and 3TC or FTC -containing regimen for >= 2 months - Plasma HIV-1 RNA >5000 copies/ml - CD4 >100 - Documented M184V or I on genotype within 3 months of study entry - At least 3 PI-associated resistance mutations on genotype within 3 months of study entry, (including known resistance mutations at codons 10, 30, 46, 50, 54, 71, 82, 84, and 90) Exclusion Criteria: - In the opinion of the investigator a patient that is either unwilling or unable to be adherent to antiretroviral drugs - Requirement for concomitant treatment with medicines that interfere with the therapy prescribed in the study - Patients who have never taken 3TC or FTC, or with no prior documentation of the M184V mutation - Active hepatitis B infection - Vaccination within 2 weeks of entering the study - An acute opportunistic illness within 4 weeks of entering the study; chronic infections will not be excluded - Use of immunomodulatory medications such as IL-2 - Planned use of enfuvirtide, (T20) in salvage regimen, (in T20 naïve subjects) Inclusion Criteria: - HIV-1 seropositive patients >= 18 years of age - Willingness and ability to understand and sign a written informed consent and comply with the protocol procedure - Prior treatment with nucleoside reverse transcriptase inhibitors (NRTI's), non-nucleoside reverse transcriptase inhibitors (NNRTI's) and protease inhibitor (PI)-containing regimens - On a stable PI and 3TC or FTC -containing regimen for >= 2 months - Plasma HIV-1 RNA >5000 copies/ml - CD4 >100 - Documented M184V or I on genotype within 3 months of study entry - At least 3 PI-associated resistance mutations on genotype within 3 months of study entry, (including known resistance mutations at codons 10, 30, 46, 50, 54, 71, 82, 84, and 90) Exclusion Criteria: - In the opinion of the investigator a patient that is either unwilling or unable to be adherent to antiretroviral drugs - Requirement for concomitant treatment with medicines that interfere with the therapy prescribed in the study - Patients who have never taken 3TC or FTC, or with no prior documentation of the M184V mutation - Active hepatitis B infection - Vaccination within 2 weeks of entering the study - An acute opportunistic illness within 4 weeks of entering the study; chronic infections will not be excluded - Use of immunomodulatory medications such as IL-2 - Planned use of enfuvirtide, (T20) in salvage regimen, (in T20 naïve subjects) HIV Infections HIV Infections In this randomized, open-label, controlled trial, HIV-infected patients who are failing 3TC/FTC-containing highly active antiretroviral therapy, (HAART), will be offered individual treatment selection based on best clinical judgment and genotypic HIV-RNA resistance analysis. --- M184V --- --- M184V --- --- M184V ---

Inclusion Criteria: - HIV-1 seropositive patients >= 18 years of age - Willingness and ability to understand and sign a written informed consent and comply with the protocol procedure - Prior treatment with nucleoside reverse transcriptase inhibitors (NRTI's), non-nucleoside reverse transcriptase inhibitors (NNRTI's) and protease inhibitor (PI)-containing regimens - On a stable PI and 3TC or FTC -containing regimen for >= 2 months - Plasma HIV-1 RNA >5000 copies/ml - CD4 >100 - Documented M184V or I on genotype within 3 months of study entry - At least 3 PI-associated resistance mutations on genotype within 3 months of study entry, (including known resistance mutations at codons 10, 30, 46, 50, 54, 71, 82, 84, and 90) Exclusion Criteria: - In the opinion of the investigator a patient that is either unwilling or unable to be adherent to antiretroviral drugs - Requirement for concomitant treatment with medicines that interfere with the therapy prescribed in the study - Patients who have never taken 3TC or FTC, or with no prior documentation of the M184V mutation - Active hepatitis B infection - Vaccination within 2 weeks of entering the study - An acute opportunistic illness within 4 weeks of entering the study; chronic infections will not be excluded - Use of immunomodulatory medications such as IL-2 - Planned use of enfuvirtide, (T20) in salvage regimen, (in T20 naïve subjects) Inclusion Criteria: - HIV-1 seropositive patients >= 18 years of age - Willingness and ability to understand and sign a written informed consent and comply with the protocol procedure - Prior treatment with nucleoside reverse transcriptase inhibitors (NRTI's), non-nucleoside reverse transcriptase inhibitors (NNRTI's) and protease inhibitor (PI)-containing regimens - On a stable PI and 3TC or FTC -containing regimen for >= 2 months - Plasma HIV-1 RNA >5000 copies/ml - CD4 >100 - Documented M184V or I on genotype within 3 months of study entry - At least 3 PI-associated resistance mutations on genotype within 3 months of study entry, (including known resistance mutations at codons 10, 30, 46, 50, 54, 71, 82, 84, and 90) Exclusion Criteria: - In the opinion of the investigator a patient that is either unwilling or unable to be adherent to antiretroviral drugs - Requirement for concomitant treatment with medicines that interfere with the therapy prescribed in the study - Patients who have never taken 3TC or FTC, or with no prior documentation of the M184V mutation - Active hepatitis B infection - Vaccination within 2 weeks of entering the study - An acute opportunistic illness within 4 weeks of entering the study; chronic infections will not be excluded - Use of immunomodulatory medications such as IL-2 - Planned use of enfuvirtide, (T20) in salvage regimen, (in T20 naïve subjects) HIV Infections HIV Infections In this randomized, open-label, controlled trial, HIV-infected patients who are failing 3TC/FTC-containing highly active antiretroviral therapy, (HAART), will be offered individual treatment selection based on best clinical judgment and genotypic HIV-RNA resistance analysis. --- M184V --- --- M184V --- --- M184V --- --- M184V ---

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

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

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

MeSH:Heroin Dependence

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

11 A 14 Day Randomized, Double Blind, Study of Once Daily Elvucitabine Versus Lamivudine in Subjects With a Documented M184V Mutation

HIV-1 infected patients receiving long-term therapy with lamivudine or emtricitabine (nucleoside reverse transcriptase inhibitors [NRTIs]) are at risk for the development of a mutation at position M184 on the HIV reverse transcriptase gene. This mutation confers resistance to both drugs (> 100 fold increase in IC50). In-vitro studies with elvucitabine have shown that HIV-1 isolates with the M184V mutation show only a 10-fold increase in IC50 as compared to wild type HIV-1. Achillion Pharmaceutical's intention is to demonstrate that 10 mg of elvucitabine, administered once per day for 14 days with continued background anti-HIV-1 medications, will demonstrate a fall in HIV-1 RNA plasma levels, as compared to baseline. The data from this study will guide dosing in future long-term studies in HIV-1 infected patients with the M184V mutation.

NCT00312039 HIV Infections Drug: elvucitabine Drug: Lamivudine

MeSH:HIV Infections

A 14 Day Randomized, Double Blind, Study of Once Daily Elvucitabine Versus Lamivudine in Subjects With a Documented M184V Mutation. --- M184V ---

Study of Once Daily Elvucitabine Versus Lamivudine in Subjects With a Documented M184V Mutation HIV-1 infected patients receiving long-term therapy with lamivudine or emtricitabine (nucleoside reverse transcriptase inhibitors [NRTIs]) are at risk for the development of a mutation at position M184 on the HIV reverse transcriptase gene. --- M184V ---

In-vitro studies with elvucitabine have shown that HIV-1 isolates with the M184V mutation show only a 10-fold increase in IC50 as compared to wild type HIV-1. --- M184V ---

The data from this study will guide dosing in future long-term studies in HIV-1 infected patients with the M184V mutation. --- M184V ---

Inclusion Criteria: - Clinically stable HIV-1 infected patients - Ages > 18 and < 65 years - Documented M184V mutation - CD4 cell count > 100 cells/mL - Plasma HIV-1 RNA levels > 5000 and < 150,000 copies/mL - Currently receiving lamivudine or emtricitabine - Other hematologic and metabolic parameters must be met. --- M184V ---

HIV Infections HIV Infections Protocol Title: A 14-Day, Randomized, Double-Blind, Comparative Viral Kinetic Study of Elvucitabine Versus Lamivudine Administered Once Daily to HIV-1 Infected Subjects With a Documented M184V Variant Protocol Number: ACH443-014A Clinical Phase: 2a Primary Objectives: • To assess the viral kinetics of 10 mg of elvucitabine administered once daily (QD) for 14 days in combination with background antiretroviral therapy in HIV-1-infected subjects with a documented M184V variant - To demonstrate the antiviral activity of 10 mg of elvucitabine administered QD for 14 days in combination with background antiretroviral therapy as compared with lamivudine in combination with background antiretroviral therapy in HIV-1 infected subjects with a documented M184V variant - To assess the safety of elvucitabine therapy in HIV-1 infected subjects with a documented M184V variant Number of Subjects: 20 Number of Study Centers: Multi-center study Study Population: HIV-1 infected subjects who are presently failing an antiretroviral therapy regimen containing lamivudine or emtricitabine, genotypically demonstrate a MI84V variant, and have an HIV RNA plasma level ≥ 2,000 and ≤ 150,000 copies/mL. --- M184V ---

HIV Infections HIV Infections Protocol Title: A 14-Day, Randomized, Double-Blind, Comparative Viral Kinetic Study of Elvucitabine Versus Lamivudine Administered Once Daily to HIV-1 Infected Subjects With a Documented M184V Variant Protocol Number: ACH443-014A Clinical Phase: 2a Primary Objectives: • To assess the viral kinetics of 10 mg of elvucitabine administered once daily (QD) for 14 days in combination with background antiretroviral therapy in HIV-1-infected subjects with a documented M184V variant - To demonstrate the antiviral activity of 10 mg of elvucitabine administered QD for 14 days in combination with background antiretroviral therapy as compared with lamivudine in combination with background antiretroviral therapy in HIV-1 infected subjects with a documented M184V variant - To assess the safety of elvucitabine therapy in HIV-1 infected subjects with a documented M184V variant Number of Subjects: 20 Number of Study Centers: Multi-center study Study Population: HIV-1 infected subjects who are presently failing an antiretroviral therapy regimen containing lamivudine or emtricitabine, genotypically demonstrate a MI84V variant, and have an HIV RNA plasma level ≥ 2,000 and ≤ 150,000 copies/mL. --- M184V --- --- M184V ---

HIV Infections HIV Infections Protocol Title: A 14-Day, Randomized, Double-Blind, Comparative Viral Kinetic Study of Elvucitabine Versus Lamivudine Administered Once Daily to HIV-1 Infected Subjects With a Documented M184V Variant Protocol Number: ACH443-014A Clinical Phase: 2a Primary Objectives: • To assess the viral kinetics of 10 mg of elvucitabine administered once daily (QD) for 14 days in combination with background antiretroviral therapy in HIV-1-infected subjects with a documented M184V variant - To demonstrate the antiviral activity of 10 mg of elvucitabine administered QD for 14 days in combination with background antiretroviral therapy as compared with lamivudine in combination with background antiretroviral therapy in HIV-1 infected subjects with a documented M184V variant - To assess the safety of elvucitabine therapy in HIV-1 infected subjects with a documented M184V variant Number of Subjects: 20 Number of Study Centers: Multi-center study Study Population: HIV-1 infected subjects who are presently failing an antiretroviral therapy regimen containing lamivudine or emtricitabine, genotypically demonstrate a MI84V variant, and have an HIV RNA plasma level ≥ 2,000 and ≤ 150,000 copies/mL. --- M184V --- --- M184V --- --- M184V ---

HIV Infections HIV Infections Protocol Title: A 14-Day, Randomized, Double-Blind, Comparative Viral Kinetic Study of Elvucitabine Versus Lamivudine Administered Once Daily to HIV-1 Infected Subjects With a Documented M184V Variant Protocol Number: ACH443-014A Clinical Phase: 2a Primary Objectives: • To assess the viral kinetics of 10 mg of elvucitabine administered once daily (QD) for 14 days in combination with background antiretroviral therapy in HIV-1-infected subjects with a documented M184V variant - To demonstrate the antiviral activity of 10 mg of elvucitabine administered QD for 14 days in combination with background antiretroviral therapy as compared with lamivudine in combination with background antiretroviral therapy in HIV-1 infected subjects with a documented M184V variant - To assess the safety of elvucitabine therapy in HIV-1 infected subjects with a documented M184V variant Number of Subjects: 20 Number of Study Centers: Multi-center study Study Population: HIV-1 infected subjects who are presently failing an antiretroviral therapy regimen containing lamivudine or emtricitabine, genotypically demonstrate a MI84V variant, and have an HIV RNA plasma level ≥ 2,000 and ≤ 150,000 copies/mL. --- M184V --- --- M184V --- --- M184V --- --- M184V ---

Study Design: HIV-1 infected subjects, with a documented M184V variant, will be randomized to receive elvucitabine 10 mg QD or lamivudine 300 mg QD for 14 days. --- M184V ---

12 Evolution of L74V or K65R Mutations in VIremic Subjects on TDF or ABC (EVITA)

This is a multicenter, open-label, non-randomized, dual-arm pilot study to investigate the prevalence of the reverse transcriptase (RT) resistance mutations, K65R/x or L74V/x, in HIV-1 plasma from subjects experiencing confirmed first-time incomplete virologic suppression during treatment with an initial antiretroviral (ARV) regimen consisting of at least 12 weeks of TDF or ABC + emtricitabine (FTC) or lamivudine (3TC) + non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). Subjects will be followed until a substantial loss of virologic or immunologic control requires a treatment switch. Confirmed first-time incomplete virologic suppression is defined as an initial plasma HIV-1 RNA response < 400 copies/mL, and subsequent virologic rebound > 400 copies/mL measured at two consecutive times. Subjects will have a screening genotype to establish adherence to their non-suppressive TDF- or ABC-containing regimen by the presence of M184V (or other treatment-related primary) mutation and to demonstrate that the evolution of treatment-emergent RT mutations can be characterized. Twenty subjects (a maximum of 10 per arm) will be enrolled at 10-20 United States (U.S.) sites. If fewer than 20 subjects can be enrolled, the study may be discontinued early by the sponsor. Equal numbers of subjects on Arm A versus Arm B will be a goal.

NCT00312169 HIV Infections

MeSH:HIV Infections

Subjects will have a screening genotype to establish adherence to their non-suppressive TDF- or ABC-containing regimen by the presence of M184V (or other treatment-related primary) mutation and to demonstrate that the evolution of treatment-emergent RT mutations can be characterized. --- M184V ---

4. Screening HIV-1 genotype with M184V or at least one treatment-related primary mutation. --- M184V ---

Subjects will have screening genotype to establish adherence to their non-suppressive TDF- or ABC-containing regimen by the presence of M184V (or other treatment-related primary) mutation and to demonstrate that the evolution of treatment-emergent RT mutations can be characterized. --- M184V ---

4. Screening HIV-1 genotype with M184V or at least one treatment-related primary mutation. --- M184V ---

13 Phase IIIb Multicenter, Single Arm, Open-Label Pilot Study to Evaluate the Effectiveness and Safety of Maintenance With Atazanavir/Ritonavir as Single Enhanced Protease Inhibitor Therapy in HIV-Infected Patients Evidencing Virologic Suppression OREY (Only REYataz) Study

The main purpose is to explore whether atazanavir/ritonavir (ATV/RTV) single enhanced protease inhibitor therapy can maintain virologic suppression without a marked increase in virologic failure.

NCT00337467 Human Immunodeficiency Virus (HIV) Infections Drug: Atazanavir + Ritonavir

MeSH:Acquired Immunodeficiency Syndrome HIV Infections Immunologic Deficiency Syndromes

HPO:Immunodeficiency

Reverse Transcriptase (RT) are TAMS and M184V.. Number of Participants With Genotype Substitutions for Virologic Rebounds (HIV-RNA ≥ 400 c/mL) Through Week 96. --- M184V ---

Reverse Transcriptase (RT) are TAMS and M184V.. Inclusion Criteria: - On continued antiretroviral (ARV) treatment, with no discontinuation periods, for the previous 6 months (24 weeks). --- M184V ---

14 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 HIV Infections Drug: elvucitabine Drug: Lamivudine Drug: Tenofovir 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 ---

Subjects must be sensitive to elvucitabine, lamivudine, and emtricitabine as demonstrated by the absence of the M184V, M184I, and D237E mutations by TRUGENE HIV-1 Genotyping Kit. --- M184V ---

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

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

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

MeSH:HIV Infections

- Existence of the M184V mutation or probable presence in the cellular archives. --- M184V ---

16 GMB: Phase IV, Multicenter, Randomized, Open-Label Pilot Study of Truvada (TDF+FTC) or Emtricitabine (FTC) Alone Versus HAART Interruption in HIV-Infected Patients Who Need to Interrupt HAART and Who Are Infected With HIV Isolates Containing at Least 2 TAMs (or K65R) and M184V

Many patients who already harbor drug-resistant HIV require interruption of HAART due to poor compliance, poor quality of life, toxicity or development of resistance. In these patients interruption of HAART has a negative impact on patient immune status due to the reemergence of wild-type virus which is in general more pathogenic than HIV isolates containing resistance mutations. There is a need for "bridging" antiretroviral regimens that might prolong time off conventional HAART whilst waiting for a new regimen that is either fully suppressive or less toxic or less demanding for the patient.

NCT00362687 HIV Infections Drug: Truvada (TDF+FTC) alone Drug: FTC alone Procedure: No HAART

MeSH:HIV Infections

GMB: Phase IV, Multicenter, Randomized, Open-Label Pilot Study of Truvada (TDF+FTC) or Emtricitabine (FTC) Alone Versus HAART Interruption in HIV-Infected Patients Who Need to Interrupt HAART and Who Are Infected With HIV Isolates Containing at Least 2 TAMs (or K65R) and M184V. --- K65R --- --- M184V ---

- Available genotype (current or historical) showing M184V and (≥ 2 TAMs or K65R). --- M184V ---

17 An Open Label Long Term Safety Extension Study of Apricitabine in Treatment-experienced HIV-1 Infected Subjects

The study will examine how safe and effective apricitabine is when given long term (as ongoing treatment) to HIV patients who have already completed the AVX-201 trial

NCT00367952 HIV Infection Drug: apricitabine

MeSH:HIV Infections

Inclusion Criteria: - Completed AVX-201 protocol, Plasma HIV RNA <5000 copies/ml, CD4 cells >50 Exclusion Criteria: - Pregnant or breastfeeding females, withdrawal from AVX-201 Inclusion Criteria: - Completed AVX-201 protocol, Plasma HIV RNA <5000 copies/ml, CD4 cells >50 Exclusion Criteria: - Pregnant or breastfeeding females, withdrawal from AVX-201 HIV Infection HIV Infections An ongoing study (AVX-201) is examining the safety and efficacy of apricitabine compared to 3TC in HIV patients who are failing therapy containing 3TC and have the presence of the M184V mutation in reverse transcriptase. --- M184V ---

18 14-Day Randomized Double-Blind Comparative Viral Kinetic Study of Elvucitabine Versus Lamivudine Once Daily to HIv-1 Subjects With M184V

The purpose of this 28 day study is to assess the viral kinetics and safety of elvucitabine.

NCT00405249 HIV Infections Drug: elvucitabine

MeSH:HIV Infections

14-Day Randomized Double-Blind Comparative Viral Kinetic Study of Elvucitabine Versus Lamivudine Once Daily to HIv-1 Subjects With M184V. --- M184V ---

Inclusion Criteria: - HIV infected, clinically stable, adults - HIVRNA 5000 -150,000, CD4 100 - Genotypically documented M184V variant - Receiving stable ART. --- M184V ---

Exclusion Criteria: - Hep B - HIV-1 genotype for 4 protease inhibitors - HIV-1 genotype positive for 2 NNRTI mutations - Previous therapy with system myelosuppressive potential within 3 months of study start - Use of Epogen or Neupogen - History of cirrhosis - Alcohol or drug dependence - Inability to tolerate oral medication - Women who are pregnant or breast feeding Inclusion Criteria: - HIV infected, clinically stable, adults - HIVRNA 5000 -150,000, CD4 100 - Genotypically documented M184V variant - Receiving stable ART. --- M184V ---

Exclusion Criteria: - Hep B - HIV-1 genotype for 4 protease inhibitors - HIV-1 genotype positive for 2 NNRTI mutations - Previous therapy with system myelosuppressive potential within 3 months of study start - Use of Epogen or Neupogen - History of cirrhosis - Alcohol or drug dependence - Inability to tolerate oral medication - Women who are pregnant or breast feeding HIV Infections HIV Infections This is a 14 day on treat/14 day off treatment randomized, double blind viral kinetic study of elvucitabine versus lamivudine administered once daily to HIV infected subjects with a documented M184V variant. --- M184V ---

19 A Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerance, Pharmacokinetics and Antiviral Activity of Amdoxovir and Zidovudine in Untreated HIV-1 Infected Subjects Currently Untreated

The purpose of this study is to determine the short term safety, tolerance, and antiviral effect of zidovudine (AZT) and amdoxovir (AMDX, DAPD) in combination, and whether the dosage for AZT can be reduced, potentially decreasing side effects, while maintaining antiviral effects. Study hypothesis: DADP in combination with AZT is safe and effective, and AZT dosing may be reduced, resulting in lower levels of AZT-monophosphate associated with toxicity and maintaining levels of AZT-triphosphate associated with efficacy.

NCT00432016 HIV Infections Drug: zidovudine Drug: amdoxovir Procedure: pharmacokinetic sampling

MeSH:HIV Infections

Therefore, second line treatments that are currently in development should provide activity against resultant mutations, primarily M184V/I (17%) and much less commonly K65R (0 to 5%), and ideally prevent or be effective against mutations that may occur during second line therapy. --- M184V ---

DAPD has increased sensitivity to M184V/I strains and is active against thymidine analog mutations (TAMs) that may have occurred during previous antiretroviral regimens. --- M184V ---

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

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

NCT00511368 HIV Infections Drug: matching placebo Drug: Bevirimat

MeSH:HIV Infections

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

- 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 ---

21 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 --- --- M184V ---

22 Once-daily Antiretroviral Therapy in HIV-1 Infected Patients With CD4+ Cell Counts Below 100 Cells/Mcl. A Prospective, Randomized, Multicentre, Open Clinical Study.

There are few randomized clinical trials in advanced HIV patients. This is a multicenter, randomized, open clinical trial, comparing three parallel groups, to compare the immunological reconstitution and the virological efficacy and safety of three different combinations of antiretroviral therapy given once a day (QD): tenofovir plus emtricitabine plus either efavirenz, lopinavir-ritonavir or atazanavir-ritonavir during 96 weeks in advanced antiretroviral naïve HIV-1 infected patients with less than 100 CD4+ T-cells/mm3. Primary endpoint is the median increase in CD4+ T-cell count at 48 weeks after starting HAART.

NCT00532168 HIV Infections Drug: tenofovir + emtricitabine + efavirenz Drug: tenofovir + emtricitabine + lopinavir-ritonavir Drug: tenofovir + emtricitabine + atazanavir-ritonavir

MeSH:HIV Infections

- No mutations of drug resistance at baseline (M184V/I, K65R, resistance to efavirenz or 2 or more PRAMs (L33I/F/V, V82A/F/L/T, I84V, L90M) - Written informed consent Exclusion Criteria: - Hypersensibility to study drugs. --- M184V ---

23 Parallel Comparison of Tenofovir and Emtricitabine/Tenofovir Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition Within HIV-1 Discordant Couples

Randomized, blinded, placebo-controlled trial to demonstrate if pre-exposure prophylaxis decreases HIV-1 acquisition among HIV-1 uninfected individuals within HIV-1 discordant couples.

NCT00557245 HIV-1 Infections HIV Infections Drug: Tenofovir Disoproxil Fumarate (TDF) Drug: Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) Drug: Placebo

MeSH:Infection Communicable Diseases HIV Infections

HIV-1 resistance as measured by the number of seroconverters who had an HIV-1 reverse transcriptase mutation (K65R, K70E, M184I, or M184V) conferring resistance to TDF or FTC. --- K65R --- --- K70E --- --- M184I --- --- M184V ---

24 A Phase 2b/3, Randomized, Double Blind, Dose Confirming Study of the Safety, Efficacy and Tolerability of Apricitabine Versus Lamivudine in Treatment-experienced HIV-1 Infected Patients With the M184V/I Mutation in Reverse Transcriptase

Apricitabine is a new NRTI which is active against drug-resistant HIV. NRTIs are often included as part of patients' treatment, but many HIV-infected patients develop resistance to commonly used NRTIs such as lamivudine (3TC) and emtricitabine (FTC). This study will examine whether including apricitabine as part of patients' treatment is more effective than including lamivudine,when patients change treatment because of drug resistance.

NCT00612898 HIV Infections Drug: apricitabine Drug: lamivudine

MeSH:Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome

A Phase 2b/3, Randomized, Double Blind, Dose Confirming Study of the Safety, Efficacy and Tolerability of Apricitabine Versus Lamivudine in Treatment-experienced HIV-1 Infected Patients With the M184V/I Mutation in Reverse Transcriptase. --- M184V ---

Inclusion Criteria: - HIV-1 positive with M184V/I mutation in reverse transcriptase; - 18 years of age or older; - Currently taking lamivudine (3TC) or emtricitabine (FTC) Exclusion Criteria: - Female patients who are pregnant or breastfeeding; - Current hepatitis B virus (HBV) infection; - Current treatment for hepatitis C virus infection; - Renal function not adequate Inclusion Criteria: - HIV-1 positive with M184V/I mutation in reverse transcriptase; - 18 years of age or older; - Currently taking lamivudine (3TC) or emtricitabine (FTC) Exclusion Criteria: - Female patients who are pregnant or breastfeeding; - Current hepatitis B virus (HBV) infection; - Current treatment for hepatitis C virus infection; - Renal function not adequate HIV Infections Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome ATC has potent antiviral activity both in vitro (against wild-type HIV-1 and HIV-1 with mutations in reverse transcriptase that confer resistance to NRTIs), and in clinical studies in both treatment-naïve and treatment-experienced patients with M184V, including in the presence of additional NRTI mutations in reverse transcriptase. --- M184V ---

Inclusion Criteria: - HIV-1 positive with M184V/I mutation in reverse transcriptase; - 18 years of age or older; - Currently taking lamivudine (3TC) or emtricitabine (FTC) Exclusion Criteria: - Female patients who are pregnant or breastfeeding; - Current hepatitis B virus (HBV) infection; - Current treatment for hepatitis C virus infection; - Renal function not adequate Inclusion Criteria: - HIV-1 positive with M184V/I mutation in reverse transcriptase; - 18 years of age or older; - Currently taking lamivudine (3TC) or emtricitabine (FTC) Exclusion Criteria: - Female patients who are pregnant or breastfeeding; - Current hepatitis B virus (HBV) infection; - Current treatment for hepatitis C virus infection; - Renal function not adequate HIV Infections Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome ATC has potent antiviral activity both in vitro (against wild-type HIV-1 and HIV-1 with mutations in reverse transcriptase that confer resistance to NRTIs), and in clinical studies in both treatment-naïve and treatment-experienced patients with M184V, including in the presence of additional NRTI mutations in reverse transcriptase. --- M184V --- --- M184V ---

Inclusion Criteria: - HIV-1 positive with M184V/I mutation in reverse transcriptase; - 18 years of age or older; - Currently taking lamivudine (3TC) or emtricitabine (FTC) Exclusion Criteria: - Female patients who are pregnant or breastfeeding; - Current hepatitis B virus (HBV) infection; - Current treatment for hepatitis C virus infection; - Renal function not adequate Inclusion Criteria: - HIV-1 positive with M184V/I mutation in reverse transcriptase; - 18 years of age or older; - Currently taking lamivudine (3TC) or emtricitabine (FTC) Exclusion Criteria: - Female patients who are pregnant or breastfeeding; - Current hepatitis B virus (HBV) infection; - Current treatment for hepatitis C virus infection; - Renal function not adequate HIV Infections Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome ATC has potent antiviral activity both in vitro (against wild-type HIV-1 and HIV-1 with mutations in reverse transcriptase that confer resistance to NRTIs), and in clinical studies in both treatment-naïve and treatment-experienced patients with M184V, including in the presence of additional NRTI mutations in reverse transcriptase. --- M184V --- --- M184V --- --- M184V ---

The M184V mutation is most commonly present amongst patients failing regimens containing either of the two deoxycytidine analogs lamivudine and emtricitabine. --- M184V ---

Whilst lamivudine therapy is often maintained in patients harboring the M184V mutation in some settings, there are no deoxycytidine analogs currently available that effectively suppress replication of HIV-1 containing the M184V/I mutation, particularly in the presence of other additional NRTI mutations. --- M184V ---

Whilst lamivudine therapy is often maintained in patients harboring the M184V mutation in some settings, there are no deoxycytidine analogs currently available that effectively suppress replication of HIV-1 containing the M184V/I mutation, particularly in the presence of other additional NRTI mutations. --- M184V --- --- M184V ---

The purpose of this study is to extend the efficacy and safety established in study AVX-201 of ATC in patients who are HIV-1 infected and have failed treatment with lamivudine or emtricitabine and have confirmed M184V/I mutation. --- M184V ---

25 A Phase 3, Open Label 96-week Extension Study of the Safety of Apricitabine in Treatment-experienced HIV-1 Infected Patients Who Have Completed Protocol AVX-301 or AVX-302 or Who Have Met the Criteria for Open-label Access to ATC Because of Virological Failure/Lack of Response

This study will examine the long term safety of apricitabine in HIV-1 infected patients from studies AVX-301 or AVX-302. Eligible patients are those who have either (a)completed studies AVX-301 or AVX-302; or (b)met the criteria for virological failure/lack of response, and consequently wish to withdraw early from studies AVX-301 or AVX-302.

NCT00686270 HIV Infections Drug: apricitabine

MeSH:Infection HIV Infections

Exclusion Criteria: - Prior withdrawal from AVX-301 or AVX-302 - Current acute or chronic hepatitis B virus infection - Current treatment for hepatitis C virus infection - Renal Function not adequate HIV Infections Infection HIV Infections The clinical study AVX-301 studies the efficacy and safety of 800mg and 1200mg BID ATC in combination with an optimized background in patients who are HIV-1 infected and have failed treatment with emtricitabine or lamivudine and have confirmed M184V/I mutation. --- M184V ---

26 Phase 2B Safety and Effectiveness Study of Tenofovir 1% Gel, Tenofovir Disproxil Fumarate Tablet and Emtricitabine/Tenofovir Disoproxil Fumarate Tablet for the Prevention of HIV Infection in Women

A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate (TDF) and emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) are oral, FDA-approved, anti-HIV drugs, and tenofovir gel is an experimental microbicide. The purpose of this study is to determine the safety and effectiveness of daily tenofovir 1% gel compared to a vaginal placebo gel, and the safety and effectiveness of oral TDF and oral FTC/TDF compared to an oral placebo in preventing HIV infection among women at risk for sexually transmitted infections.

NCT00705679 HIV Infections Drug: Emtricitabine/tenofovir disoproxil fumarate Drug: Emtricitabine/tenofovir disoproxil fumarate placebo Drug: Tenofovir disoproxil fumarate Drug: Tenofovir disoproxil fumarate placebo Drug: Tenofovir 1% vaginal gel Drug: Tenofovir placebo

MeSH:Infection HIV Infections Acquired Immunodeficiency Syndrome

The primary resistance mutations for the study were pre-defined as K65R and K70E (which confer resistance to TDF), and M184I and M184V (which confer resistance to FTC), for their potential to cause a decrease in susceptibility to the study drug. --- K65R --- --- K70E --- --- M184I --- --- M184V ---

The number of HIV-1 seroconverters while on study with the M184V resistance mutation are reported for this outcome measure.. Inclusion Criteria: - Willing to provide adequate locator information - Sexually active, defined as having vaginal intercourse at least once in the 3 months prior to screening - Agree to not participate in other research studies involving drugs, medical devices, or vaginal products for duration of study. --- M184V ---

27 A Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Ritonavir-Boosted Elvitegravir (EVG/r) Versus Raltegravir (RAL) Each Administered With a Background Regimen in HIV-1 Infected, Antiretroviral Treatment-Experienced Adults

The purpose of this study is to compare the safety, tolerability and efficacy of a regimen containing once-daily elvitegravir (EVG) versus twice-daily raltegravir (RAL) added to a background regimen (1 fully-active ritonavir (RTV)-boosted protease inhibitor (PI) plus 1 or 2 additional antiretroviral (ARV) agents) in HIV-1 infected, ARV treatment-experienced adults who have documented resistance, or at least six months experience prior to screening with two or more different classes of ARV agents. Participants will be randomized in a 1:1 ratio to receive EVG plus background regimen (Elvitegravir group), or raltegravir plus background regimen (Raltegravir group). Due to known drug interactions, participants in the Elvitegravir group receiving RTV-boosted atazanavir (ATV) or RTV-boosted lopinavir (LPV) as part of their background regimen will receive elvitegravir at a lower dose (85 mg).

NCT00708162 HIV Infection Drug: Elvitegravir Drug: Raltegravir Drug: EVG placebo Drug: RAL placebo Drug: Background regimen

MeSH:HIV Infections

If the M184V/I reverse transcriptase (RT) mutation is present on the screening genotype report and an NRTI is used as the second agent, then either FTC or LAM may be added as a third agent in the background regimen to maintain the M184V/I mutation. --- M184V ---

If the M184V/I reverse transcriptase (RT) mutation is present on the screening genotype report and an NRTI is used as the second agent, then either FTC or LAM may be added as a third agent in the background regimen to maintain the M184V/I mutation. --- M184V --- --- M184V ---

28 A Prospective, Randomized, Open Label Phase IV Study to Evaluate the Rationale of Switching From Fixed Dose Abacavir (ABC)/Lamivudine (3TC) to Fixed Dose Tenofovir DF (TDF)/Emtricitabine (FTC) in Virologically Suppressed, HIV-1 Infected Patients Maintained on a Ritonavir Boosted Protease Inhibitor Containing Antiretroviral Regimen

This protocol describes a prospective, randomized, open-label, multicenter study to evaluate the safety and efficacy of switching from fixed dose abacavir (ABC)/lamivudine (3TC) to fixed dose emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) in virologically suppressed, human immunodeficiency virus type 1 (HIV-1) infected subjects maintained on a ritonavir-boosted protease inhibitor (PI/r)-containing antiretroviral (ARV) regimen. Duration of treatment is 48 weeks.

NCT00724711 HIV Infection Drug: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) Drug: abacavir (ABC)/lamivudine (3TC)

MeSH:HIV Infections

- Adequate renal function defined as a calculated CLcr greater than or equal to 50 mL/min according to the Cockcroft-Gault formula - Negative serum pregnancy test (females of childbearing potential only) - Hepatic transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 5 X upper limit of normal - Males and females (of childbearing potential, ie, a non-menopausal female or a female with menopause < 2 years, and who has not had a hysterectomy, bilateral oophorectomy, or medically documented ovarian failure; this definition includes a young woman who has not yet started menstruating), and must agree to avoid pregnancy by sexual abstinence, or utilization of a highly effective method of birth control throughout the study period and for 30 days following discontinuation of study drug - The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of any study procedures Exclusion Criteria: - Subjects receiving ABC/3TC and a PI without ritonavir - Subjects receiving other ARV agents (eg, 2 protease inhibitors boosted with low-dose ritonavir (ie, "double-boosted PI regimens"), nonnucleoside reverse transcriptase inhibitors [NNRTIs], integrase inhibitors, TDF, or other nucleoside reverse transcriptase inhibitor [NRTIs]) in addition to ABC/3TC and a ritonavir-boosted protease inhibitor - Have known resistance to any of the study agents at any time in the past including NRTI resistance mutations (including but not limited to K65R, L74V/I, M184V/I, or thymidine analog mutations) and/or PI resistance mutations - A new acquired immunodeficiency syndrome (AIDS) defining condition diagnosed (with the exception of CD4 criteria) within 30 days of baseline - Previous therapy with agents with systemic myelosuppressive, pancreatoxic, hepatotoxic or cytotoxic potential within 3 months of study start or the expected need for such therapy at the time of enrollment - Proven or suspected acute hepatitis in the 30 days prior to study entry - Anticipated need to initiate drugs during the study that are contraindicated with protease inhibitors (except upon approval by Gilead) - Receiving ongoing therapy with any of the following (administration of any of the following medications must be discontinued at least 30 days prior to the Baseline visit and for the duration of the study period): - Nephrotoxic agents (aminoglycoside antibiotics, amphotericin B, cidofovir, cisplatin, foscarnet, intravenous pentamidine, other agents with significant nephrotoxic potential) - Adefovir dipivoxil - Probenecid - Systemic chemotherapeutic agents (ie, cancer treatment medications) - Systemic corticosteroids - Interleukin-2 (IL-2) - Investigational agents (except upon approval by Gilead) - Pregnant or lactating subjects - Evidence of a gastrointestinal malabsorption syndrome or chronic nausea or vomiting which may confer an inability to receive an orally administered medication - Current alcohol or substance abuse judged by the investigator to potentially interfere with subject adherence - Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma. --- K65R --- --- L74V --- --- M184V ---

29 A Multicenter, Open-label, Randomized Study to Assess the Metabolics, Efficacy, and Safety of Once-daily Darunavir Versus Atazanavir in HIV-infected Treatment-naive Adult Patients

The purpose of this research study is to compare changes in triglyceride and other lipids (levels of fats found in the blood) from Baseline (Day 1) to Week 12 for darunavir/ritonavir 800/100 mg once daily versus atazanavir/ritonavir 300/100 mg once daily in combination with a fixed-dose background regimen consisting of emtricitabine [FTC]/tenofovir [TDF] 200/300 mg once daily). This study will also evaluate the safety (adverse events), effectiveness, and tolerability of darunavir/ritonavir and atazanivir/ritonavir over 48 weeks.

NCT00757783 HIV Drug: ritonavir Drug: ritonavir Drug: darunavir Drug: emtricitabine [FTC]/tenofovir [TDF] Drug: emtricitabine [FTC]/tenofovir [TDF] Drug: atazanavir

Number of participants with antiviral activity, HIV-1 RNA, missing values as treatment failure (Missing = Failure) were observed.. Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48.. the HIV-1 RNA viral load was calculated using Log Base 10 transformed HIV-1 RNA observed values.. Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values.. Participants' Cluster of Differentiation (CD) 4 Cell Count were at baseline and the change values at Week 12 and 48 were observed.. Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF).. Participants' Cluster of Differentiation (CD) 4 Cell Count were observed at baseline and the change values at Week 12 and 48 was calculated using LOCF.. Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF).. Participants' Cluster of Differentiation (CD) 4 percent were observed at baseline and the change values at Week 12 and 48 was calculated using LOCF.. Inclusion Criteria: - HIV-1 RNA of 1000 copies/mL or more - No previous treatment with antiretroviral drugs for more than 10 days - Demonstrated sensitivity [Fold Change (FC) = lower Clinical Cut Off (CCO)] to tenofovir, darunavir and atazanavir - Demonstrated sensitivity to emtricitabine defined as absence of M184V/I mutation - Any CD4 (Cluster of Differentiation 4) cell count Exclusion Criteria: - Body mass index >30 kg/m2 - Laboratory parameters as follows: fasting glucose >110 mg/dL, Low-Density Lipoprotein (LDL) cholesterol >130 mg/dL, triglycerides >200 mg/dL - Presence of any currently active AIDS-defining illness - Treatment for primary HIV infection or postexposure prophylaxis for HIV - Patients with acute or chronic hepatitis A, B or C infection Inclusion Criteria: - HIV-1 RNA of 1000 copies/mL or more - No previous treatment with antiretroviral drugs for more than 10 days - Demonstrated sensitivity [Fold Change (FC) = lower Clinical Cut Off (CCO)] to tenofovir, darunavir and atazanavir - Demonstrated sensitivity to emtricitabine defined as absence of M184V/I mutation - Any CD4 (Cluster of Differentiation 4) cell count Exclusion Criteria: - Body mass index >30 kg/m2 - Laboratory parameters as follows: fasting glucose >110 mg/dL, Low-Density Lipoprotein (LDL) cholesterol >130 mg/dL, triglycerides >200 mg/dL - Presence of any currently active AIDS-defining illness - Treatment for primary HIV infection or postexposure prophylaxis for HIV - Patients with acute or chronic hepatitis A, B or C infection HIV The purpose of this study is to expand our understanding of the metabolic effects of darunavir/ritonavir (DRV/r) in HIV-infected patients. --- M184V ---

Number of participants with antiviral activity, HIV-1 RNA, missing values as treatment failure (Missing = Failure) were observed.. Change From Baseline in HIV-1 RNA Viral Load at Week 12 and 48.. the HIV-1 RNA viral load was calculated using Log Base 10 transformed HIV-1 RNA observed values.. Change From Baseline in CD4 Cell Count at Week 12 and 48, Observed Values.. Participants' Cluster of Differentiation (CD) 4 Cell Count were at baseline and the change values at Week 12 and 48 were observed.. Change From Baseline in Cluster of Differentiation (CD) 4 Cell Count at Week 12 and 48, Last Observation Carried Forward (LOCF).. Participants' Cluster of Differentiation (CD) 4 Cell Count were observed at baseline and the change values at Week 12 and 48 was calculated using LOCF.. Change From Baseline in Cluster of Differentiation (CD) 4 Percent at Week 12 and 48, Last Observation Carried Forward (LOCF).. Participants' Cluster of Differentiation (CD) 4 percent were observed at baseline and the change values at Week 12 and 48 was calculated using LOCF.. Inclusion Criteria: - HIV-1 RNA of 1000 copies/mL or more - No previous treatment with antiretroviral drugs for more than 10 days - Demonstrated sensitivity [Fold Change (FC) = lower Clinical Cut Off (CCO)] to tenofovir, darunavir and atazanavir - Demonstrated sensitivity to emtricitabine defined as absence of M184V/I mutation - Any CD4 (Cluster of Differentiation 4) cell count Exclusion Criteria: - Body mass index >30 kg/m2 - Laboratory parameters as follows: fasting glucose >110 mg/dL, Low-Density Lipoprotein (LDL) cholesterol >130 mg/dL, triglycerides >200 mg/dL - Presence of any currently active AIDS-defining illness - Treatment for primary HIV infection or postexposure prophylaxis for HIV - Patients with acute or chronic hepatitis A, B or C infection Inclusion Criteria: - HIV-1 RNA of 1000 copies/mL or more - No previous treatment with antiretroviral drugs for more than 10 days - Demonstrated sensitivity [Fold Change (FC) = lower Clinical Cut Off (CCO)] to tenofovir, darunavir and atazanavir - Demonstrated sensitivity to emtricitabine defined as absence of M184V/I mutation - Any CD4 (Cluster of Differentiation 4) cell count Exclusion Criteria: - Body mass index >30 kg/m2 - Laboratory parameters as follows: fasting glucose >110 mg/dL, Low-Density Lipoprotein (LDL) cholesterol >130 mg/dL, triglycerides >200 mg/dL - Presence of any currently active AIDS-defining illness - Treatment for primary HIV infection or postexposure prophylaxis for HIV - Patients with acute or chronic hepatitis A, B or C infection HIV The purpose of this study is to expand our understanding of the metabolic effects of darunavir/ritonavir (DRV/r) in HIV-infected patients. --- M184V --- --- M184V ---

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

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

NCT00959894 HIV Infections Drug: Etravirine (Intelence) Drug: Truvada

MeSH:Infection Communicable Diseases HIV Infections Acquired Immunodeficiency Syndrome

2. Any of the following NRTI mutations: M184V/I, K70E/R, K65R, M41L, 69 insert, L210W, T215Y/F, K219Q/E, L74V. --- M184V ---

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

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

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

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

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

32 Artery Elasticity After Switch From Epzicom to Truvada

Recent research as suggested that use of the HIV medication abacavir (Ziagen, or co-formulated with lamivudine as Epzicom) may increase risk for heart disease, though findings from multiple studies have been inconsistent. This pilot study will examine vascular function, a marker of heart disease risk, among patients taking abacavir as part of their HIV medications and are then randomized to: 1) switch to tenofovir, another HIV medication, or 2) continue to take abacavir.

NCT00998582 HIV Infections Drug: Tenofovir disoproxil

MeSH:HIV Infections

- Males and females (of childbearing potential) must agree to avoid pregnancy by sexual abstinence, or utilization of a highly effective method of birth control throughout the study period and for 30 days following discontinuation of study drug (refer to Appendix A for definitions of 'childbearing potential' and 'highly effective method of birth control') Exclusion Criteria: - Subjects with known resistance to abacavir, lamivudine, tenofovir DF, or emtricitabine at anytime in the past (including but not limited to K65R, L74V/I, M184V/I, or thymidine analog mutations). --- K65R --- --- L74V --- --- M184V ---

33 Treatment Outcomes and Plasma Level of Ritonavir-boosted Lopinavir Monotherapy Among HIV-infected Patients Who Had Non-nucleoside Reverse Transcriptase Inhibitor (NRTI) and NNRTI Failure: A Pilot Study

To assess 48-week treatment responses, tolerability, and steady-state minimum plasma concentrations of ritonavir-boosted lopinavir monotherapy for salvage therapy in HIV-1 infected patients who failed antiretroviral regimens containing NRTI and NNRTI.

NCT01002898 HIV Drug: lopinavir/ritonavir soft gel capsule

Inclusion Criteria: 1. HIV-1 infected patients >18 years of age, 2. failed NNRTI-based antiretroviral therapy with M184V, thymidine analogue mutations (TAMs) and NNRTI-associated mutations 3. had plasma HIV-1 RNA >1,000 copies/mL. --- M184V ---

On the other hand, previous studies showed that continuation of lamivudine after emerging of the M184V mutation had somewhat benefit on immunological response and clinical progression in patients who had limited options of salvage regimens. --- M184V ---

34 A Phase 3, Randomized, Open Label, Controlled Study of Lopinavir/Ritonavir and Lamivudine Versus Standard Therapy in Naïve HIV-1 Infected Subjects.

The purpose of this study is designed to compare the safety, tolerability, antiviral activity and immunological effect of lopinavir/ritonavir plus lamivudine (3TC) versus standard therapy with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus lopinavir/ritonavir in the treatment of naïve HIV-1 infected subjects.

NCT01237444 HIV Infection Drug: lopinavir/ritonavir plus one nucleoside Drug: lopinavir /ritonavir plus two nucleosides

MeSH:HIV Infections

2. The presence of any of the following major mutations: V32I; I47V / A; L76V; V82A/F/T/S or the presence of two or more minor mutations at positions:10,20,24,33,46,50,53,54,63,71,73,84,90 is considered resistance to lopinavir/ritonavir. 3. The presence of mutation M184V/I and/or K65R is considered resistance to 3TC or FTC. --- V32I --- --- I47V --- --- L76V --- --- V82A --- --- M184V ---

35 Evaluation of 3TC or FTC Mono-therapy Compared to Continuing HAART as a Bridging Antiretroviral Strategy in Persistently Non-adherent Children, Adolescents, and Young Adults Who Are Failing HAART and Have the M184V Resistance Mutation.

The purpose of this study was to compare the use of lamivudine (3TC) or emtricitabine (FTC) alone vs. continuing a failing highly active antiretroviral therapy (HAART) regimen in HIV infected children, adolescents and young adults. The study was to see if there were changes in the HIV virus and if there were differences in immune function, viral load and medication side effects between the two groups over 28 weeks. Participants were assigned to either take 3TC or FTC alone or continue on his/her current failing HAART regimen. During the first 28 weeks of this study, if the participant was randomized to the continue HAART arm, he/she was not switched to a different or new, potentially suppressive HAART regimen, but continued on the current failing HAART regimen. However, if continuing HAART, the participant might be switched to a new regimen if their provider felt that it was clinically needed or the participant met certain study endpoints (e.g., drop in CD4, increase in viral load). At the end of 28 weeks, the participant had the choice of remaining on the assigned study group medication(s) or starting a new HAART regimen prescribed by his/her doctor. Then, they would be followed for another 24 weeks to compare the difference in immune function, viral load and medication side effects between the different groups.

NCT01338025 HIV Disease Drug: HAART regimen Drug: 3TC or FTC monotherapy

MeSH:Acquired Immunodeficiency Syndrome HIV Infections

Evaluation of 3TC or FTC Mono-therapy Compared to Continuing HAART as a Bridging Antiretroviral Strategy in Persistently Non-adherent Children, Adolescents, and Young Adults Who Are Failing HAART and Have the M184V Resistance Mutation.. Evaluation of 3TC or FTC Mono-therapy Compared to Continuing HAART as a Bridging Strategy The purpose of this study was to compare the use of lamivudine (3TC) or emtricitabine (FTC) alone vs. continuing a failing highly active antiretroviral therapy (HAART) regimen in HIV infected children, adolescents and young adults. --- M184V ---

- CD4+ T cell count greater than or equal to 100 cells/mm3 (confirmed on at least two occasions within 6 months of study entry, including the screening value) - Documentation of the M184V mutation on genotypic testing at any time prior to study entry - In the best judgment of the clinical site team, concerns about the subject's ability to adhere made it unsuitable to initiate a new optimal HAART regimen for at least 6 months. --- M184V ---

36 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 ---

Recent data suggest that patients with isolated M184V-related NRTI resistance who subsequently switch to a boosted PI plus lamivudine (3TC)- or emtricitabine (FTC)-based regimen may achieve HIV-1 RNA suppression without the need to switch to more complex regimens [1]. --- M184V ---

Detection of an isolated M184V NRTI mutation is possible when resources allow for early diagnosis of virologic failure. --- M184V ---

37 Safety and Efficacy of Switching a Stable Combined Antiretroviral Therapeutic Regimen to Atazanavir With Ritonavir Plus Lamivudine in Treatment Experienced HIV Positive Patients With Full and Stable Virological Suppression

The purpose of this study is to evaluate the virological efficacy of maintenance therapy with atazanavir with ritonavir combined with lamivudine in treatment experienced HIV positive patients with full and stable virological suppression.

NCT01599364 Human Immunodeficiency Virus Drug: Atazanavir, ritonavir, lamivudine

MeSH:Acquired Immunodeficiency Syndrome HIV Infections

- Treated with a cART regimen containing atazanavir boosted with ritonavir since at least 3 months - With full virological suppression (VL<50 copies/mL) for a minimum of six months and in at least in two consecutive determination 3 months +/-2 weeks apart from each other - With CD4 cell count >200 since at least 6 months and without opportunistic infections or other AIDS-related events since at least one year before screening Exclusion Criteria: - Previous virological failure on a lamivudine- or PI-containing regimen or previous exposure to lamivudine-containing suboptimal antiretroviral regimens - Patients with at least a single viral load blip over 200 copies/mL - Patients with M184V or major atazanavir resistance mutation at previous genotypic resistance test (historical genotype) - Pregnancy or lactation, planned pregnancy in the short-term - Patients with HBsAg positive chronic HBV infection - Patients who experienced major toxicities related to any of the study drugs in the past - Patients with grade 4 laboratory abnormalities at baseline (excluding lipid profile and plasma bilirubin concentration). --- M184V ---

Lamivudine is a well tolerated NRTI which showed no significant toxicity in the short and long term and, together with its analog emtricitabine, is now a preferred option in most of the major international treatment guidelines; it has a good CNS penetration score and its only signature resistance mutation (M184V) deeply impairs the viral fitness and does not compromise the future treatment options. --- M184V ---

38 An Open-Label Phase 3B Study in HIV-Infected Individuals With Viremia on or After Their First-Line Non-Nucleoside Reverse Transcriptase Inhibitor or Integrase Inhibitor-Based Regimen and Starting a Second-Line Regimen Consisting of ATV/RTV or DRV/RTV With an Optimized NRTI Backbone

The purpose of this study is to determine the proportion of subjects with HIV-1 RNA < 50 c/mL at Week 48 in patients who failed their first line therapy containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) or an integrase inhibitor

NCT01605084 HIV Drug: Atazanavir Drug: Darunavir Drug: Ritonavir Drug: Optimized NRTI backbone

Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 48 by baseline M184V presence or absence. --- M184V ---

39 An Open Label Randomized Clinical Trial, to Evaluate the Treatment With Darunavir/Ritonavir + Lamivudine Once Daily Versus Continuing With Darunavir/Ritonavir Once Daily + Tenofovir/Emtricitabine or Abacavir/Lamivudine in HIV Infected Subject With Suppressed Plasma Viremia

This is an open label randomized clinial trial to evaluate the treatment with darunavir/ritonavir (800mg/100mg) plus lamivudine (300 mg) once daily versus continuing with darunavir/ritonavir (800mg/100mg) once daily plus tenofovir/emtricitabine (300mg/200mg) or abacavir/lamivudine (600mg/300mg) in HIV infected subject with suppressed plasma viremia.

NCT02159599 HIV Infection Drug: Darunavir/Ritonavir Drug: Lamivudine Drug: Emtricitabine/tenofovir or abacavir/lamivudine

MeSH:HIV Infections

3. Treatment with darunavir/ritonavir once a day and tenofovir/emtricitabine or abacavir/lamivudine during at least 4 weeks at the moment of the screening 4. Plasma HIV RNA levels below 50 copies / ml for at least 6 months (two separate measurements at least 6 months with viremia <50 copies / ml between both). 5. HbsAg negative Exclusion Criteria: 1. Pregnant or breastfeeding woman 2. Evidence of Lamivudine resistance (any previous genotype with mutation M184V/I or K65R) and/or to darunavir (population genotype show any of the following mutations: V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, T74P, L76V, I84V, L89V). --- M184V ---

40 A Randomized, Open Label, Phase 4 Study Evaluating the Renal Effect of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir DF or Other Tenofovir DF-containing Regimens (Ritonavir-boosted Atazanavir Plus Emtricitabine/Tenofovir DF or Efavirenz/Emtricitabine/Tenofovir DF) Compared to Ritonavir-boosted Atazanavir Plus Abacavir/Lamivudine in Antiretroviral Treatment-naïve HIV-1 Infected Adults With eGFR ≥70 mL/Min

The primary objective of this study is to assess glomerular function before and during administration of stribild (STB; elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF)) or a regimen containing TDF without cobicistat (COBI) as ritonavir (RTV)-boosted atazanavir (ATV/r) plus truvada (TVD; FTC/TDF) or atripla (ATR; efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF)) compared to a regimen containing neither TDF nor COBI as ATV/r plus abacavir/lamivudine (ABC/3TC) via determination of actual glomerular filtration rate (aGFR) using iohexol (a probe GFR marker) plasma clearance and estimated (calculated) glomerular filtration rate (eGFR).

NCT02246998 HIV-1 Infection Drug: STB Drug: TVD Drug: ATR Drug: RTV Drug: ATV Drug: ABC/3TC Drug: Iohexol

The most severe graded abnormality from all tests was counted for each participant.. Key Inclusion Criteria: - Treatment naïve - Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at Screening - CD4 cell count > 200 cells/µL - Screening genotype report provided by the site must show sensitivity to FTC, TDF, EFV, ABC, 3TC, ATV and absence of study drug resistance mutations that include K65R, K70E and M184V in RT - Estimated GFR ≥ 70 mL/min - Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) ≤ 5 × upper limit of normal (ULN) - Total bilirubin ≤ 1.5 mg/dL (≤ 26 umol/L), or normal direct bilirubin - Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL) - Serum amylase ≤ 5 × ULN (individuals with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN) - Normal electrocardiogram (ECG) or not clinically significant if abnormal ECG - Not pregnant or non-lactating females of non-childbearing potential. --- K65R --- --- K70E --- --- M184V ---

Key Inclusion Criteria: - Treatment naïve - Plasma HIV-1 RNA levels ≥ 5,000 copies/mL at Screening - CD4 cell count > 200 cells/µL - Screening genotype report provided by the site must show sensitivity to FTC, TDF, EFV, ABC, 3TC, ATV and absence of study drug resistance mutations that include K65R, K70E and M184V in RT - Estimated GFR ≥ 70 mL/min - Hepatic transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) ≤ 5 × upper limit of normal (ULN) - Total bilirubin ≤ 1.5 mg/dL (≤ 26 umol/L), or normal direct bilirubin - Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL) - Serum amylase ≤ 5 × ULN (individuals with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN) - Normal electrocardiogram (ECG) or not clinically significant if abnormal ECG - Not pregnant or non-lactating females of non-childbearing potential. --- K65R --- --- K70E --- --- M184V ---

41 Management of Participants With Low-level Persistent Viremia (ANRS 161 L-VIR)

Management of participants with low-level persistent viremia

NCT02247687 HIV-1 Infection Treatment Resistant Disorders Viremia Drug: Protease inhibitor Drug: Isentress® (raltegravir) Other: Counseling arm

MeSH:Viremia

- Participant naïve to raltegravir (RAL) - failure of amplification or successful realization of genotypic resistance test without evidence for resistance mutations against current treatment (3TC/FTC accepted with M184V mutation) - creatinin < 3 Upper Limit normal (ULN) - Aspartate Amino Transférase (ASAT), Alanine Amino Transférase (ALAT) < 5 Upper Limit normal (ULN) - hemoglobin > 8 g/dL - platelets > 50 000/mm3 - In women, lack of current pregnancy verified by Beta Human Chorionic Gonadotropin (βHCG) at week -4 visit and use of a mechanical contraceptive method - Informed consent - Participants with an active health insurance coverage (article L1121-11 du Code de la Santé Publique) Exclusion Criteria: - HIV-2 infection, - severe medical condition in the last month (inclusion is possible for a stable condition at screening) - breastfeeding women, current pregnancy or planned pregnancy within 12 months. --- M184V ---

42 Effect of SwitChing AtriPla to Eviplera on Neurocognitive and Emotional Functioning, ESCAPE Study

This study will evaluate the effects of switching Atripla to Eviplera on neurocognition measured by neuropsychological testing and functional MRI

NCT02308332 Neurocognitive Decline HIV Associated Neurocognitive Disorder Drug: Eviplera

MeSH:Neurocognitive Disorders

Differences in mean changes between baseline and end of study, as well as between the two study groups will be calculated using a paired T-test.. Inclusion Criteria: - Male, between 30 and 50 years - HIV-1 RNA < 50 copies/mL on screening visit - on Atripla continuously for ≥6 months preceding the screening visit - Have a HIV genotype prior to starting cART with Atripla with no known resistance to any of the study agents at any time in the past including, but not limited to RT mutations K65R, K101E/P, E138G/K/Q/R, Y181C/I/V, M184V/I and H221Y - Negative TPHA or VDRL < 12 months prior to the screening visit - no signs of an acute or chronic hepatitis C infection within the past 12 months before screening as defined in the Dutch guideline (Arends et al. --- K65R --- --- K101E --- --- E138G --- --- Y181C --- --- M184V ---

Inclusion Criteria: - Male, between 30 and 50 years - HIV-1 RNA < 50 copies/mL on screening visit - on Atripla continuously for ≥6 months preceding the screening visit - Have a HIV genotype prior to starting cART with Atripla with no known resistance to any of the study agents at any time in the past including, but not limited to RT mutations K65R, K101E/P, E138G/K/Q/R, Y181C/I/V, M184V/I and H221Y - Negative TPHA or VDRL < 12 months prior to the screening visit - no signs of an acute or chronic hepatitis C infection within the past 12 months before screening as defined in the Dutch guideline (Arends et al. --- K65R --- --- K101E --- --- E138G --- --- Y181C --- --- M184V ---

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

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

NCT02507921 HIV Drug Resistance

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

44 Safety and Efficacy of Emtricitabine/Tenofovir Alafenamide as Part of Salvage Antiretroviral Regimens in Patients With Uncontrolled Viremia and Drug-Resistant HIV Infection

Background: HIV attacks the immune system. Antiretroviral therapy (ART) is a combination of drugs used for treating HIV infection. For some people, ART drugs stop working against their HIV. Researchers want to see if a different form of the drug tenofovir (an ART drug currently approved by the FDA), combined with another drug, may help people whose HIV is resistant to ART. This combination pill is called F/TAF Objective: To study the safety and efficacy of the drug F/TAF, when used with other ART, for people whose HIV infection has been hard to control with available medicines. Eligibility: People age 14 years and older who have HIV infection and are enrolled in the DOTCOM (14-I-0009) protocol. Design: Participants will be screened with physical exam, medical history, and blood and urine tests. Participants will stay in the hospital for at least 10 days. For the first 9 days, they will take F/TAF by mouth along with their usual ART drugs. In the hospital, they will repeat the screening tests. Participants will have a DEXA scan, an x-ray that measures calcium and other minerals in the bones. Participants will lie on a soft table while the scanner passes over the lower spine and hips. Participants will get a supply of F/TAF and some new ART drugs to take at home. Participants will have follow-up visits in 1, 2, 4, 8, and 12 weeks. After the 12-week visit, they will come back about every 3 months for about 1 year. At these visits, participants will repeat the screening tests. They will discuss any problems taking their ART drugs. They may have another DEXA scan.

NCT02556333 HIV Drug: FTC/TAF

- Where neither TDF nor ABC are optimal NRTI options as defined by at least one of the following criteria: - Presence of the M184V mutation plus TDF-associated resistance mutations based on genotypic/phenotypic testing, specifically K65R alone, or with TAMs (such as 41L, 67N, 70R, 210W, 215Y/F, or 219Q/E) with or without other NRTI-associated mutations; or - FTC/TDF is not considered an option due to impaired renal function (eGFR by Cockroft-Gault equation [eGFR(CG)]=30-60 mL/min), or risk of renal impairment because of conditions such as uncontrolled hypertension, diabetes mellitus, or history of renal toxicity while receiving a TDF-based regimen; and where ABC/3TC is contraindicated (ie, presence of HLA B*5701 allele or history of hypersensitivity reaction to ABC), or is a suboptimal option (eg, presence of ABC-associated resistance mutation(s) or in patients with HBV co-infection). --- M184V ---

45 A Phase 3, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Boosted Atazanavir or Darunavir Plus Either Emtricitabine/Tenofovir or Abacavir/Lamivudine to GS-9883/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed HIV-1 Infected Adults

The primary objective of this study is to evaluate the efficacy of switching to a fixed-dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing on a regimen consisting of boosted atazanavir (ATV) or darunavir (DRV) plus either emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or abacavir/lamivudine (ABC/3TC) in HIV-1 infected adults who are virologically suppressed.

NCT02603107 HIV-1 Infection Drug: RTV Drug: ATV Drug: DRV Drug: COBI Drug: ATV/co Drug: DRV/co Drug: FTC/TDF Drug: ABC/3TC Drug: B/F/TAF

(If the lower limit of detection of the local HIV-1 RNA assay is < 50 copies/mL [e.g., < 20 copies/mL], the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests) - Have no documented or suspected resistance to FTC, tenofovir, ABC or 3TC, including but not limited to the reverse transcriptase resistance mutations K65R and M184V/I - No previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) Key Exclusion Criteria: - An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening - Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) - Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine based therapies) - Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance - A history of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. --- K65R --- --- M184V ---

46 A Phase 3b, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Switching From Regimens Consisting of Abacavir/Lamivudine (ABC/3TC) Plus a Third Antiretroviral Agent to the Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed HIV 1 Infected Adult Subjects

The primary objective of this study is to evaluate the efficacy of switching to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) relative to continuing on a baseline regimen consisting of abacavir/lamivudine (ABC/3TC) plus a 3rd antiretroviral agent in HIV-1 infected participants.

NCT02605954 HIV-1 Infection Drug: E/C/F/TAF Drug: ABC/3TC Drug: Third Antiretroviral Agent

MeSH:Infection

- All documented historical plasma genotype(s) must not show resistance to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC), including, but not limited to the presence of reverse transcriptase resistance mutants K65R, K70E, M184V/I, or thymidine analog associated mutations (TAMs) (TAMs are: M41L, D67N, K70R, L210W, T215Y/F, K219Q/E/N/R). --- K65R --- --- K70E --- --- M184V ---

47 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

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. --- M184V ---

Study to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) in Virologically-Suppressed HIV-1 Infected Adults 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. --- M184V ---

Study to Evaluate Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Fixed Dose Combination (FDC) in Virologically-Suppressed HIV-1 Infected Adults 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. --- M184V --- --- M184V ---

Key Inclusion Criteria: - Documented historical genotype report showing mutation M184V and/or M184I (mixtures are acceptable) in reverse transcriptase. --- M184V ---

- 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 ---

- 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 --- --- M184V ---

48 A Phase 3b, Randomized, Open-Label Study to Evaluate Switching From a Tenofovir Disoproxil Fumarate (TDF) Containing Regimen to Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Infected Subjects Aged ≥ 60 Years

The primary objective of this study is to evaluate the safety of elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (E/C/F/TAF) relative to unchanged current antiretroviral therapy (ART) by assessing spine and hip bone mineral density (BMD) measured at Week 48 in virologically-suppressed, HIV-1 infected participants aged ≥ 60 years.

NCT02616783 HIV-1 Infection Drug: E/C/F/TAF Drug: TDF Drug: FTC Drug: FTC/TDF Drug: 3TC Drug: Third agent

MeSH:Infection

- Plasma HIV-1 RNA level < 50 copies/mL at screening visit - Adequate renal function - Estimated glomerular filtration rate ≥ 30 mL/min according to the Cockcroft-Gault formula (eGFRCG) and are on ARVs that are appropriately dose adjusted for renal function per package insert - All documented historical plasma genotype(s) must not show resistance to TDF or FTC, including, but not limited to the presence of reverse transcriptase resistance mutations K65R, K70E, M184V/I, or thymidine analog-associated mutations (TAMs) that include M41L, L210W, D67N, K70R, T215Y/F, K219Q/E/N/R. --- K65R --- --- K70E --- --- M184V ---

49 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 HIV-1 Infection HCV Infection Drug: E/C/F/TAF Drug: F/R/TAF 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 ---

50 A Phase 2b/3 Double Blind Safety and Efficacy Study of Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC), For Pre-Exposure Prophylaxis in HIV-Uninfected Cisgender Men and Transgender Women Who Have Sex With Men

This study will evaluate the safety and efficacy of the injectable drug cabotegravir (CAB LA), for pre-exposure prophylaxis (PrEP) in HIV-uninfected cisgender men and transgender women who have sex with men (MSM and TGW).

NCT02720094 HIV Infections Drug: Cabotegravir tablets Drug: TDF/FTC tablets Drug: TDF/FTC placebo tablets Drug: CAB placebo tablets Drug: CAB LA Drug: Placebo for CAB LA

MeSH:HIV Infections

Incidence of resistance mutations to study products (including but not limited to K65R, M184V/I, Q148R) among seroconverters. --- K65R --- --- M184V ---

51 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 ---

52 A Phase 2/3, Open-Label Study of the Pharmacokinetics, Safety, and Antiviral Activity of the GS-9883/Emtricitabine/Tenofovir Alafenamide (GS-9883/F/TAF) Fixed Dose Combination (FDC) in HIV-1 Infected Virologically Suppressed Adolescents and Children

Cohort 1 and 2: The primary objectives of this study are: Part A: - To evaluate the steady state pharmacokinetics (PK) of bictegravir (BIC) and confirm the dose of the bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed dose combination (FDC) in HIV-1 infected, virologically suppressed adolescents (12 to < 18 years of age) and children (6 to < 12 years of age) Parts A and B: - To evaluate the safety and tolerability of the adult strength B/F/TAF FDC through Week 24 in HIV-1 infected, virologically suppressed adolescents (12 to <18 years of age) and children (6 to <12 years of age) Cohort 3: The primary objectives of this study are: Part A: - To evaluate the steady state PK of BIC and confirm the dose of B/F/TAF 30/120/15 mg FDC in HIV-1 infected, virologically suppressed children ≥ 2 years of age weighing ≥ 14 to < 25 kg Parts A and B: - To evaluate the safety and tolerability of the low dose B/F/TAF FDC tablet through Week 24 in HIV-1 infected, virologically suppressed children ≥ 2 years of age weighing ≥ 14 to < 25 kg

NCT02881320 HIV-1 Infection Drug: B/F/TAF (Adult Strength) Drug: B/F/TAF (Low Dose)

m^2 according to the Schwartz Formula - No documented or suspected resistance to emtricitabine (FTC), tenofovir (TFV), or integrase strand transfer inhibitors (INSTIs) including, but not limited to, the reverse transcriptase resistance mutations K65R and M184V/I Note: Other protocol defined Inclusion/Exclusion criteria may apply. --- K65R --- --- M184V ---

53 Evaluation of a Simplified Strategy for the Long-term Management of HIV Infection: a Non-inferiority, Randomized, Controlled, Open-label Clinical Trial

The purpose of this study is to evaluate whether maintenance antiretroviral therapy could be simplified to DTG + FTC dual therapy and/or patient-centered monitoring once virological suppression is achieved. Using a factorial design, the study aims to assess the efficacy of DTG + FTC dual therapy to maintain virological suppression through 48 weeks of follow-up as well as the costs of a patient-centered ART laboratory monitoring.

NCT03160105 HIV-1-infection Antiretroviral Therapy Maintenance Therapy Drug: Switch to DTG + FTC Other: Patient-centered monitoring

MeSH:Infection Communicable Diseases HIV Infections

Note: patients with documented genotype(s) presenting only a M184V mutation remain eligible; 3. Creatinine clearance < 50ml/min; 4. ASAT or ALAT >2.5x upper limit of the norm; 5. Known hypersensitivity, intolerance or allergy to DTG or FTC; 6. Known or suspected non-adherence (defined as <80% adherence, i.e. missed doses > 1x/week) to current treatment in the last 6 months; 7. Concomitant use of drugs that decrease DTG blood concentrations including carbamazepine, oxcarbamazepine, phenytoin, phenobarbital, St John's wort and rifampicin; 8. Women who are pregnant or breast-feeding; 9. a. Presence of any INSTI-resistance. --- M184V ---

54 Antiretroviral Treatment Guided by Proviral Genotype: Pilot Trial of Proof of Concept.

Phase IIa, open clinical trial, pilot, single arm and proof of concept.

NCT03539224 HIV-1-infection Drug: Dolutegravir (DTG) Drug: Lamivudine (3TC)

For those included in group 1 (20 patients): No previous history of virological failure with ART regimen that included 3TC or FTC or previous virological failure had a population genotype without M184V/I or K65R/E/N mutations. --- M184V ---

For those included in group 2 (20 patients): previous history of virological failure with ART regimen that included 3TC or FTC and historical genotype with M184V/I or K65R/E/N mutations. --- M184V ---

Detection of any of the following mutations in proviral DNA in peripheral blood by conventional sequencing: M184V/I or K65R/E/N. --- M184V ---

Half of the participants will have history of failure with 3TC or FTC and M184V/I or K65R/E/N mutations in previous plasma genotypes, although to be eligible these mutations cannot be detectable at study entry in proviral DNA. --- M184V ---

55 Effect of Reducing Nucleotide Exposure on Bone Health (ReNew)

This is an open-label, randomized pilot study to assess the effect on bone mineral density (BMD) of a switch from a tenofovir alafenamide-containing antiretroviral regimen to dolutegravir/lamivudine vs. a continuation of the tenofovir alafenamide-containing regimen.

NCT03549689 HIV/AIDS HIV-1-infection Osteopenia Drug: Dolutegravir (DTG) 50MG/lamivudine (3TC) 300MG FIXED DOSE COMBINATION (FDC) Drug: Current tenofovir alafenamide (TAF)-containing ART regimen

MeSH:Bone Diseases, Metabolic

HPO:Osteopenia

Any antiretroviral history (even before routine virologic monitoring became standard of care) that would suggest the presence of the M184V mutation should be considered exclusionary 7. ALT ≥5 X ULN, OR ALT ≥3xULN and bilirubin ≥1.5xULN (with >35% direct bilirubin) 8. Severe hepatic impairment (Child Pugh Class C) 9. Anticipated need for antiviral therapy for HCV 10. --- M184V ---

56 A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching From a Regimen of Two Nucleos(t)Ide Reverse Transcriptase Inhibitors (NRTI) Plus a Third Agent to a Fixed Dose Combination (FDC) of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF), in Virologically-Suppressed, HIV-1 Infected African American Participants

The primary objective of this study is to evaluate the efficacy of switching from a regimen of 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) and a third agent to a fixed dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing their baseline regimen in HIV-1 infected, virologically suppressed African American participants.

NCT03631732 HIV-1 Infection Drug: B/F/TAF Drug: NRTIs Drug: Third Agent

- History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other RT substitutions are allowed, with the following exceptions: History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT will be excluded. --- M184V ---

57 Phase I/II Study of the Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in HIV-1-Infected Children Less Than 12 Years of Age

The purpose of this study is to examine the pharmacokinetics, safety, and tolerability of abacavir/dolutegravir/lamivudine dispersible and immediate release tablets in HIV-1-infected children less than 12 years of age.

NCT03760458 HIV Infections Drug: Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Dispersible Tablets Drug: Abacavir (ABC)/Dolutegravir (DTG)/Lamivudine (3TC) Immediate Release Tablets (Immediate release)

MeSH:HIV Infections

- Based on parent or guardian report at entry, child is expected to be available for 48 weeks of follow-up - Parent or legal guardian is willing and able to provide written informed consent for child's study participation and, when applicable per local institutional review board/ethics committee (IRB/EC) policies and procedures, child is willing and able to provide written informed assent for study participation Exclusion Criteria: - Documented resistance to ABC, DTG, or 3TC - Note: Testing to rule out resistance is not required, and the M184V resistance mutation is not exclusionary. --- M184V ---

58 A Phase 1b, Open-label Study to Evaluate the PK, Safety and Efficacy of B/F/TAF in HIV-1 Infected, Virologically Suppressed, Pregnant Women in Their Second and Third Trimesters

The primary objective of this study is to evaluate the steady state pharmacokinetics of bictegravir (BIC) and confirm the dose of BIC/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg fixed dose combination (FDC) in HIV-1 infected, virologically suppressed pregnant women in their second and third trimesters.

NCT03960645 HIV-1-infection Drug: B/F/TAF

Key Inclusion Criteria: - The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures - With singleton pregnancy, at least 12 weeks but not more than 31 weeks pregnant at the time of screening - Agree not to breastfeed for the duration of the study - Currently on a stable antiretroviral regimen for ≥ 6 months preceding the screening visit - Documented plasma HIV-1 RNA levels of < 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at the screening visit - Have no documented or suspected resistance to FTC, Tenofovir (TFV), or integrase strand-transfer inhibitors (INSTIs) including, but not limited to, the reverse transcriptase resistance mutations K65R or M184V/I - Historic genotype reports will be collected if available - Have a normal ultrasound, completed locally prior to the Day 1 visit, with no evidence of any fetal malformation or structural abnormality affecting either fetus or placenta - Normal maternal alfa-fetoprotein level at the screening visit Key Exclusion Criteria: - Have chronic hepatitis B virus (HBV) - Have active hepatitis C virus (HCV) infection - An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening Note: Other protocol defined Inclusion/Exclusion criteria may apply. --- K65R --- --- M184V ---

59 AntiRetroviral Therapy In Second-line: Investigating Tenofovir-lamivudine-dolutegravir (ARTIST): a Randomised Controlled Trial

The strategy to support virological suppression on second-line antiretroviral treatment (ART) includes the provision of ART that has a low pill burden, good tolerability, low toxicity, is easily monitored, has a high barrier to resistance, and that is low cost. The fixed-dose combination of tenofovir-lamivudine-dolutegravir offers significant advantage as a potential second-line regimen compared to the World Health Organization standard of care second-line regimen of zidovudine-lamivudine-dolutegravir, in terms of cost, tolerability and monitoring requirements. The ARTIST study is a phase 2, randomised, double-blind, placebo-controlled trial aiming to determine the proportion of patients achieving virological suppression when recycling the tenofovir-emtricitabine/lamivudine backbone with dolutegravir (tenofovir-lamivudine-dolutegravir fixed-dose combination) as a second-line with and without a lead-in supplementary dose of dolutegravir, in patients failing a tenofovir-emtricitabine/lamivudine-efavirenz first-line regimen. There is evidence to suggest that even in the presence of resistance mutations to tenofovir and lamivudine (K65R or M184V/I), using this backbone with dolutegravir will provide an effective second-line regimen in patients who have failed a first-line regimen of tenofovir-emtricitabine/lamivudine-efavirenz. The strategy of giving a lead-in supplementary dose of dolutegravir is in view of the inducing effect of efavirenz on dolutegravir metabolism and transport that persists for 2 weeks after efavirenz is stopped; the inducing effect decreases with time after efavirenz is stopped. Given that these patients will have elevated viral loads, a high baseline risk of nucleoside reverse transcriptase inhibitor (NRTI) resistance and efavirenz resistance, and the inducing effect of efavirenz on dolutegravir metabolism and transport that persists for 2 weeks, this study will comprise two stages. The first stage will evaluate virological suppression in 62 participants initiated on the fixed-dose combination of tenofovir-lamivudine-dolutegravir with a lead-in supplementary dose of dolutegravir for the first 14 days. The study will progress to the second stage if this strategy proves effective, and 130 participants will then be randomised to receive the fixed-dose combination of tenofovir-lamivudine-dolutegravir with and without this lead-in dose. The primary endpoint is virological suppression (viral load <50 copies/mL) at 24 weeks. A pharmacokinetic sub-study will be conducted on 12 participants in stage 1 and 24 participants in stage 2, to assess the trough concentrations of dolutegravir and off-treatment concentrations of efavirenz at day 3, 7, 14, and 28. This is to evaluate the need for the lead-in supplementary dose of dolutegravir.

NCT03991013 HIV Infections Drug: Dolutegravir 50 mg Drug: Placebo

MeSH:HIV Infections

There is evidence to suggest that even in the presence of resistance mutations to tenofovir and lamivudine (K65R or M184V/I), using this backbone with dolutegravir will provide an effective second-line regimen in patients who have failed a first-line regimen of tenofovir-emtricitabine/lamivudine-efavirenz. --- K65R --- --- M184V ---

60 Switch to Tenofovir Alafenamide (TAF), Emtricitabine (FTC), Bictegravir (BIC)(Biktarvy®) in HIV-1-infected Patients Over 65 Years Old at Risk of Polymedication

Patients infected and living with HIV are getting older and have more and more non-HIV co-morbidities. These expose them to polypharmacy that increases the risk of pharmacological interaction. Bictegravir, co-formulated with emtricitabine (FTC) and tenofovir alafenamide (TAF) (BIKTARVY) a new generation integrase inhibitor with a high genetic barrier and had no drug interaction may be a treatment of choice for participant over 65 years old who are HIV infected . BIKTARVY improve adherence and quality of life; and on the other hand it would limit the risks of pharmacological interaction. In addition, the use of TAF reducing the risk of long-term renal toxicity and adverse effects on bone would be of interest in this aging population and more at risk of osteoporosis.

NCT04222283 HIV Infections Drug: BIKTARVY 50Mg-200Mg-25Mg Tablet

MeSH:HIV Infections

The reverse transcriptase resistant mutations M184V plus one TAM are allowed. --- M184V ---

- If no genotype is available, DNA genotype will be performed at screening visit: no resistance mutation to integrase inhibitors, the reverse transcriptase resistant mutations M184V plus one TAM are allowed. --- M184V ---

61 A Phase 4, Single-arm, Open-label Study to Evaluate the Efficacy and Safety of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) Once Daily Fixed-dose Combination (FDC) Regimen in Antiretroviral Treatment-experienced Human Immunodeficiency Virus Type 1 (HIV-1) Infected Subjects Not Currently Receiving Any Antiretroviral Therapy.

The purpose of this study is to demonstrate the effectiveness of Symtuza® in a rapid reinitiation model of care in patients with HIV-1 infection and who are treatment-experienced but have been off of antiretroviral therapy (ART) for 12 or more weeks.

NCT04388904 HIV-1-infection Drug: Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (FDC)

MeSH:Infection

- Known resistance to any of the components of D/C/F/TAF; subjects with known or identified FTC resistance attributed to an M184V mutation alone will be permitted to remain in the study. --- M184V ---

62 Dynamics of Drug Resistance-associated Mutations in HIV-1 DNA Reverse Transcriptase Clearance During Effective Antiretroviral Therapy

In view of the prolongation of patients living with HIV's life expectancy, the question of optimization of ART, which is still a life-long treatment, becomes central. While most patients achieve virological success, their treatments often need to be optimized in order to limit adverse events, drugs interactions and to improve adherence. The switch to dual regimen strategies represent one of the approaches for treatment optimization. Circulating HIV-1 resistant variants can be archived in viral reservoirs, where they can persist for an unknown duration and reemerge in case of therapeutic selective pressure. There is a need to assess the dynamic of archived Drug resistance associated mutations (DRAMs) clearance in cell-associated HIV DNA after a long period of virological control, in the perspective of ARVs recycling. The investigators postulate that it could be interesting in the future to recycle ARV drugs (that where classified as "resistant" in the past) in subsequent regimen. The question is particularly important for 3TC/FTC for subsequent new regimen and for the use of dual regimen (disappearance of M184V). Thus, the investigators propose a retrospective, longitudinal analysis on blood-cell-associated HIV-1 DNA samples in order to investigate by Sanger and Ultra Deep Sequencing the dynamics of decay and persistence of DNA HIV-1 variants harboring key drug resistance-associated mutations to NRTIs, in particular M184V, in patients with sustained virological control for at least 5 years under effective ART.

NCT04448158 HIV-1-infection Diagnostic Test: Genotypic Resistance Test

The question is particularly important for 3TC/FTC for subsequent new regimen and for the use of dual regimen (disappearance of M184V). --- M184V ---

Thus, the investigators propose a retrospective, longitudinal analysis on blood-cell-associated HIV-1 DNA samples in order to investigate by Sanger and Ultra Deep Sequencing the dynamics of decay and persistence of DNA HIV-1 variants harboring key drug resistance-associated mutations to NRTIs, in particular M184V, in patients with sustained virological control for at least 5 years under effective ART. --- M184V ---

Detection of M184V mutation. --- M184V ---

The persistence of M184V resistance mutation is defined by the detection of this mutation in 2 consecutive samples by Sanger and by a percentage of this mutation > 1% in 2 consecutive samples by UltraDeep Sequencing. --- M184V ---

The clearance of M184V is defined by the detection of this mutation by Sanger in a sample and the absence in the subsequent sample or a percentage of this mutation > 1% in a sample and a percentage < 1% in the subsequent sample.. Percentage of M184V mutation. --- M184V ---

The clearance of M184V is defined by the detection of this mutation by Sanger in a sample and the absence in the subsequent sample or a percentage of this mutation > 1% in a sample and a percentage < 1% in the subsequent sample.. Percentage of M184V mutation. --- M184V --- --- M184V ---

Inclusion Criteria: - HIV-1 infected - Age ≥ 18 years - Genotypic resistance test performed at time of failure and harboring at least M184V - Fully suppressed HIV viral load for at least 5 or 10 years. --- M184V ---

63 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 --- --- M184I --- --- M184V ---

HPO Nodes