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

Conditions

1. HIV Infections

Interventions

1. Drug: Racivir, a non-nucleoside reverse transcriptase inhibitor

MeSH:HIV Infections

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

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

Conditions

1. HIV Infections

Interventions

1. Drug: nelfinavir
2. Drug: lopinavir/r
3. Drug: indinavir
4. Drug: ritonavir

MeSH:HIV Infections

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

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

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

NCT00300573

Conditions

1. HIV Infections
2. Human Immunodeficiency Virus

Interventions

1. Drug: Dexelvucitabine

MeSH:HIV Infections Acquired Immunodeficiency Syndrome

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

Open label, two year study of the clinical efficacy of the combination of FTC, Tenofovir, and Nevirapine. Sixty HIV infected patients without previous exposure to antiretroviral therapy will be enrolled. Study will include a pharmacokinetic substudy to evaluate the interaction of FTC and Nevirapine. Truvada may be used.

NCT00344461

Conditions

1. HIV

Interventions

1. Drug: Nevirapine, FTC, and Tenofovir

Evidence of mutation associated with primary drug resistance to Nevirapine (K103N, Y181C, Y188L, G190S), Tenofovir (M41L, T69 insertion, Q151M, L210W,and K65R), and/or FTC (184V) previously documented, or at time of screening. --- K103N --- --- Y181C --- --- Y188L --- --- G190S --- --- M41L --- --- Q151M ---

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

NCT00491556

Conditions

1. HIV Infections

Interventions

1. Procedure: Early Initiation of Highly Active Anti-Retroviral Therapy
2. Procedure: Standard Care

MeSH:HIV Infections

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

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

Conditions

1. HIV Infections

Interventions

1. Drug: darunavir 800 mg
2. Drug: FTC 200 mg/TDF 300mg
3. Drug: Maraviroc
4. Drug: Raltegravir
5. 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 ---

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

Conditions

1. HIV-1 Infections

Interventions

1. Drug: TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily
2. Drug: TDF/FTC + Efavirenz (Atripla) Once-Daily

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

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

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

NCT01013987

Conditions

1. HIV-1 Adults Patients
2. AIDS
3. Triple Class Failure

Interventions

1. Drug: maraviroc
2. Drug: Raltegravir
3. Drug: Darunavir/ritonavir

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

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

Conditions

1. HIV-1 Infection

Interventions

1. Drug: Lopinavir/ritonavir
2. Drug: Lopinavir/ritonavir
3. Drug: Raltegravir
4. Drug: Emtricitabine/tenofovir disoproxil fumarate
5. Drug: Abacavir/lamivudine/zidovudine
6. Drug: Abacavir/lamivudine
7. Drug: Lamivudine/zidovudine
8. Drug: Abacavir
9. Drug: Zidovudine
10. Drug: Lamivudine

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

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

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

NCT01737359

Conditions

1. Human Immunodeficiency Virus Infection

Interventions

1. Drug: amdoxovir 300 mg bid
2. Drug: amdoxovir 500 mg bid
3. Drug: tenofovir DF 300 mg qd

MeSH:Acquired Immunodeficiency Syndrome HIV Infections

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

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

NCT01967940

Conditions

1. HIV
2. HIV Infections
3. Acquired Immunodeficiency Syndrome

Interventions

1. Drug: TAF
2. Drug: Placebo
3. Drug: E/C/F/TAF
4. Drug: Current failing ARV regimen
5. Drug: ATV

MeSH:HIV Infections Acquired Immunodeficiency Syndrome Immunologic Deficiency Syndromes

HPO:Immunodeficiency

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

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

NCT01968551

Conditions

1. HIV-1
2. HIV Infections
3. Acquired Immunodeficiency Syndrome

Interventions

1. Drug: E/C/F/TAF
2. Drug: DRV
3. Drug: Baseline DRV- containing ARV regimen

MeSH:HIV Infections Acquired Immunodeficiency Syndrome Immunologic Deficiency Syndromes

HPO:Immunodeficiency

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

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

Conditions

1. HIV-1 Infection

Interventions

1. Drug: E/C/F/TAF

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

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

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

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

Conditions

1. HIV-1 Infection

Interventions

1. Drug: darunavir/ritonavir
2. Drug: Lamivudine
3. Drug: emtricitabine-tenofovir(FTC/TDF)

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

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

NCT04495348

Conditions

1. HIV-1-infection
2. Weight Gain

Interventions

1. Drug: Doravirine

MeSH:Body Weight Weight Gain

HPO:Increased body weight

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

COMEBACK is an investigator-initiated, 48-week study. The study will be conducted in 100 persons living with HIV (PLWH) who have been off ART for two or more weeks. All enrolled participants will be prescribed Biktarvy, if determined appropriate upon review of past historical resistance tests, for use throughout the study period. Participants will also complete a series of Patient Reported Outcomes (PROs) at screening and be assigned one of three tiers of case management intervention (Piggyback, Got Your Back, Backbone), with each tier increasing in intensity regarding intervention techniques and options provided. Participants will be assessed for virologic suppression, retention in care, and PROS throughout study follow up and at study end.

NCT04519970

Conditions

1. Hiv

Interventions

1. Behavioral: Case Management

No history of primary integrase inhibitor mutations, >3 TAMs, K70E, Q151M, T69 insertion, or K65R + M184V/I on prior resistance testing 2. Drug-drug interactions with Biktarvy 3. Pregnancy 4. Unable or unwilling to provide consent for study participation 5. Any condition that, in the opinion of the Investigator of Record (IoR), would make participation in the study unsafe, complicate interpretation of outcome data, or otherwise interfere with achieving the study objective. --- K70E --- --- Q151M ---