HIV-1 Infection

Women are an underrepresented population in clinical studies on HIV and antiretroviral therapy. This study aims to help bridge this gap by providing real-world data on therapeutic management with B/F/TAF (Biktarvy) in an exclusively female cohort, aiming to improve treatment personalization and the early identification of risk factors for poor retention and treatment failure in this population. This study is single-center, ambispective observational. The retrospective component analyzes medical record data from June 2019 (the date BIC/FTC/TAF became available in Italy) to the study data cutoff. The prospective component involves data collection during routine follow-up visits up to December 31, 2027. No diagnostic or therapeutic procedures beyond standard clinical practice are involved. The study opulation includes adult women (≥18 years of age) with a confirmed diagnosis of HIV-1 infection who have received at least one prescription for BIC/FTC/TAF at the Infectious Diseases Unit of E.O. Ospedali Galliera in Genoa from June 2019 to the present, with a documented follow-up of at least 6 months. The primary objective of the study is to determine the 12- and 24-month retention-in-care rates among women treated with B/F/TAF (Biktarvy) and to identify factors associated with treatment maintenance and predictors of treatment discontinuation. Secondary objectives of the study include: * Percentage of women achieving/maintaining virologic suppression (\<50 copies/mL) at 12 and 24 months during B/F/TAF treatment * Evaluation of treatment persistence with B/F/TAF across different age groups * Analysis of reasons for discontinuing B/F/TAF (adverse events, patient choice, planned switch, other) * Identification of factors associated with virologic failure during B/F/TAF therapy * Evaluation of the impact of menopausal status (pre- vs. post-menopause) on retention and virologic outcomes * Analysis of the effect of the menopausal transition during follow-up on outcomes * Correlation of past virologic history (nadir CD4, peak viremia, previous failures) with outcomes * Evaluation of the impact of prior antiretroviral treatment history (previous lines, drug classes used, documented resistance) * Analysis of demographic and socioeconomic variables associated with treatment persistence and virologic success

The purpose of this study is to use information technology (IT) to support the efficient delivery of HIV prevention and care best practices in the dental care setting.

The purpose of this study is to evaluate the safety, tolerability, and efficacy of combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).

The objectives of this study are as follows: To evaluate the clinical performance of the TruPlex test using capillary blood, EDTA whole blood, EDTA plasma, and SST serum samples collected by trained operators in point-of-care settings To evaluate the usability of the TruPlex test through: Structured usability assessments, via a questionnaire, completed by trained operators in point-of-care settings. To assess user interpretation accuracy through a contrived result interpretation questionnaire, where intended users evaluate a set of pre-defined test results (e.g., strong/weak positives, negatives, invalids). To monitor test system reliability, including invalid rates.

Among those with hypertension, persons living with HIV (PWH) have a 50% higher risk of incident myocardial infarction compared to the general population, and they often fail to meet evidence-based treatment goals for hypertension. An important contributing factor for insufficient blood pressure control is non-adherence to antihypertensive medications. Research on medication adherence for PWH has largely focused on antiretroviral therapy adherence with limited focus on adherence to other non-AIDS condition medications. With a large proportion of PWH in the U.S. achieving viral suppression, providers may now have an opportunity to focus on the management of non-AIDS conditions like hypertension. However, because PWH who have achieved suppression have reduced clinic encounters (once or twice a year) there is potential loss of opportunity to effectively monitor and intensify hypertension treatment as needed an important opportunity to focus on preventing cardiovascular disease. CVD and other non-AIDS comorbidities. The study's overarching goal is to improve the hypertension outcomes for PWH on suppressive ART to reduce cardiovascular disease risk. In this study, we will identify and evaluate healthcare and patient-level factors that must be addressed in an intervention to increase hypertension medication adherence for PWH who have achieved viral suppression. We will use these factors to tailor an intervention and assess the feasibility and acceptability at the Duke ID clinic.

Master Protocol: The main goal of this master clinical study is to evaluate the safety, tolerability, efficacy, and pharmacokinetic (PK) of long-acting oral (LAO) regimens in people with HIV-1 (PWH). The main goal of this Substudy-01 is to assess the safety, tolerability, effectiveness, and PK of switching to weekly LAO regimens, including GS-3242 + LEN, versus continuing on once daily oral bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®) in PWH with controlled HIV infection, B/F/TAF for at least 6 months prior to study start. The primary objective is to evaluate the efficacy of switching to each LAO regimen versus continuing B/F/TAF in virologically suppressed PWH at Week 24.

Protocol title: "Efficacy and safety of doravirine in the rapid initiation of highly active antiretroviral therapy (HAART) in HIV-1positive patients without prior treatment."

This is a dual arm (arm 1 and arm 2) multi-centric non-randomized (prospective) study. Two new multicentric cohorts will be set up in 4 Belgian HIV reference centers (UZ Gent, UZ Brussel, University Hospital Liege and St. Pierre Hospital Brussels): cohort 1 will comprise PLWH in whom ART was initiated during acute HIV infection minimum 3 years ago but no more than 10 years ago (short-term ART cohort); cohort 2 will comprise PLWH on ART since \>20 years (long-term ART cohort). Participants will be included based on suppressed viremia and uninterrupted ART since initiation. Participants will undergo one blood sampling and one leukapheresis. In and exclusion criteria are described below.

Protocol Number: FH-94 Study Objetives: Primary: * To evaluate the virological response to Dolutegravir/Lamivudine in naive pregnant women with HIV who are starting antiretroviral therapy and vertical transmission in exposed neonates. Secondary: * To evaluate the incidence of maternal adverse events. * To evaluate perinatal outcomes at delivery. * To evaluate maximum virological suppression at delivery. * To evaluate the incidence of changes in body weight exceeding what is expected for gestation. * To evaluate the immune response based on changes in CD4, CD8, and CD4/CD8 ratio values during pregnancy. * Assess baseline resistance and the development of resistance to virological failure to integrase inhibitors and INTRs during treatment with DTG+3TC or DTG+TDF/XTC or DTG+TAF/FTC. * To evaluate the incidence of HIV infection in children that breastfeed. * To evaluate safety outcomes and virological response of DTG+3TC compared to DTG+TDF/XTC or DTG+TAF/FTC. Exploratory: * To explore the non-inferiority of DTG+3TC therapy compared to DTG+TDF/XTC or DTG+TAF/FTC treatment. * To evaluate the frequency of antiretroviral therapy withdrawal or modification before delivery.

In summary, there is a compelling rationale for investigating venetoclax as an intervention to sensitise virus-expressing cells to apoptosis and thereby reduce the size of the latent HIV reservoir. While this concept may ultimately need to be tested in the setting of concomitant latency reversal, the investigators propose to initially establish the safety of venetoclax in PLWH on ART. The investigators will use this study to also investigate effects of venetoclax monotherapy on proapoptotic pathways, immune effector function and HIV persistence in PLWH on ART and through these studies establish the rationale for subsequent studies testing venetoclax in combination with an LRA.

The goal of this clinical study is to provide continued access to the study drug(s) to children and adolescents with human immunodeficiency virus type 1 (HIV-1) who completed their participation in an applicable parent study and to monitor for adverse events. The primary objectives of this study are as follows: * To provide continued access to the study drug received in the parent protocol or switch to bictegravir/emtricitabine/tenofovir (B/F/TAF) for participants who completed a Gilead parent study evaluating drugs for HIV treatment. * To evaluate the safety of the study drug(s) in participants with HIV-1.

The study will have two portions: Phase 2 and Phase 3. Phase 2 will further have 2 parts: Part A and Part B. The goal of Phase 2, Part A is to assess the effectiveness of study drugs GS-3242 plus Lenacapavir (LEN) versus Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)), in people with HIV-1 (PWH) who are new to treatment. This will be done in Treatment Groups 1, 2 and 3 at Week 35. The goal of Phase 2, Part B is to compare the effectiveness of study drugs, GS-3242 and LEN versus B/F/TAF in Groups 4 and 3 at Week 26. The goal of Phase 3 is to assess the long-term effectiveness of study drug GS-3242 and LEN versus B/F/TAF, at Week 52. The primary objectives of this study are: Phase 2, Part A: To evaluate the efficacy of intramuscular (IM) GS-3242 plus IM LEN versus B/F/TAF in treatment-naive people with HIV-1 (PWH) in Treatment Groups 1, 2, and 3 at Week 35. Phase 2, Part B: To evaluate the efficacy of IM GS-3242 plus IM LEN versus B/F/TAF in treatment-naive PWH in Treatment Groups 4 and 3 at Week 26. Phase 3: To evaluate the efficacy of IM GS-3242 plus IM LEN versus B/F/TAF in treatment-naive PWH at Week 52.

The study will have two parts: Part A and Part B. In Part A, the goal of the study is to compare the effectiveness of switching to the study drugs GS-3242 plus Lenacapavir (LEN) versus continuing Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)), in virologically suppressed people with HIV-1 (PWH) in treatment Group 1, 2 and 3 at Week 35. In Part B the goal of the study is to compare the effectiveness of switching to the study drugs, GS-3242 and LEN versus continuing B/F/TAF in Groups 4 and 3 at Week 26. The primary objective of part A is to evaluate the efficacy of switching to intramuscular (IM) GS-3242 plus IM LEN versus continuing on B/F/TAF PWH who are virologically suppressed in treatment Groups 1, 2, and 3 at Week 35 and Part B is to evaluate the efficacy of switching to IM GS-3242 plus IM LEN versus continuing on B/F/TAF in PWH who are virologically suppressed in Treatment Groups 4 and 3 at Week 26.

This randomized clinical trial will evaluate the optimal duration of fluconazole therapy and timing of antiretroviral therapy initiation among HIV-infected persons with asymptomatic cryptococcal antigenemia and low cryptococcal antigen titers in Uganda. Participants with low-titer cryptococcal antigenemia will be followed to assess whether a shorter 10-week course of fluconazole is non-inferior to the standard 24-week fluconazole regimen for 24-week cryptococcal meningitis-free survival. Among participants eligible for antiretroviral therapy timing randomization, the study will also compare immediate antiretroviral therapy initiation with delayed initiation after 14 days to evaluate 10-week hospitalization-free survival. Participants will be followed for up to 24 weeks, with study visits and contacts to assess survival, cryptococcal meningitis, hospitalizations, adverse events, and fluconazole adherence.

Managing HIV well requires taking antiretroviral therapy (ART) every day, but many people living with HIV experience interruptions in their treatment. These pauses in medication can happen for many reasons, such as side effects, challenges with getting to the clinic, personal circumstances, stigma, or difficulties with everyday life. When HIV treatment is stopped, the viral load can increase, which may affect a person's health and make it easier for HIV to be passed on to others. Restarting treatment quickly after an interruption is important for both personal and public health. However, it can be difficult for people who miss doses to get back on treatment right away. There are often several steps and medical appointments required before restarting, such as waiting for lab results or reviewing medical history, which can cause further delays. These additional steps can make it even harder for people to re-engage and may discourage them from returning to care. The REINITIATE study is designed for people living with HIV who have not taken any antiretroviral medications for at least the last 12 weeks. The study will offer participants a way to restart their HIV therapy quickly, by beginning treatment with B/F/TAF on the same day that they return to care. B/F/TAF is a widely used, once-daily HIV regimen, and is recommended in national treatment guidelines. Researchers want to find out if this rapid restart approach is safe and effective, and whether it helps people regain control of HIV and remain in care. The study will also examine how many participants are able to keep the virus at a low level (viral suppression), stay engaged in their HIV care, and tolerate the medication after rapidly restarting treatment. In addition, the study will include interviews with some participants, to gain a better understanding of why they stopped taking their medications and what supported their return to treatment. These insights could help healthcare teams develop better ways to support people living with HIV in the future.

Women with HIV have an increased risk of having a myocardial infarction (heart attack) as compared to women without HIV. One of the mechanisms underlying the increased risk of myocardial infarction among women with HIV may involve reduced ability to increase blood flow through large and small coronary arteries at times when increased flow of oxygen-carrying blood is needed. We are conducting a study randomizing women with HIV and either diabetes, chronic kidney disease, or both to health education alone or to health education plus referral to see either an Endocrinologist or a Nephrologist in a subspecialty clinic for consideration of treatment with medication in a class known as sodium glucose transporter 2 (SGLT2) inhibitors. SGLT2 inhibitors are clinically approved for use in patients with diabetes or chronic kidney disease but have been shown to be underutilized in people with HIV. One of our key analytic aims will be to test if SGLT2 inhibitor therapy results in improved blood flow through the large and small coronary arteries among women with HIV and either diabetes, chronic kidney disease, or both but who have no history of myocardial infarction. A second aim will be to test if subspecialty clinic referral (with or without SGLT2 inhibitor therapy prescription) results in improved blood flow through the large and small coronary arteries among the same group.

Purpose: To assess the safety and tolerability of a single dose of IAP086 in persons with HIV suppressed on stable ART Participants: 30 people from UNC within 18 to 70years of age. People with HIV on ART with plasma HIV-1 RNA \< 50 copies/mL for 12 months prior to screening. Procedures (methods): The participant's standard of care ART regimen is continued throughout the study period. This study requires an overnight stay in a research unit. During the overnight stay, participants will receive a single infusion (medicine given slowly through a vein in their arm) of IAP086 and be monitored for 24 hours. Each later participant receives IAP086 at the same or a higher dose decided in advance. The dose will increase as more participants receive IAP086 without concerning side effects. Study visits also occur 2, 3, 7, 14, 21 and 28 days after the study drug is given. Study procedures include review of the medical history, physical exams, and blood draws.

The goal of this clinical study is to compare how effective a long-acting treatment of injectable combination of lenacapavir (LEN), teropavimab (TAB), and zinlirvimab (ZAB) is versus continuing a daily oral HIV treatment in adults with HIV-1 whose virus is already well controlled, after 1 year (52 weeks) of treatment. The primary objective of this study is to evaluate the efficacy of switching to the regimen of LEN, TAB, and ZAB versus continuing an oral stable baseline regimen (SBR) in virologically suppressed people with HIV-1 (PWH) as determined by the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 52.

Phase III trial evaluating doravirine as an alternative to dolutegravir in treatment naïve people living with HIV-1 infection.

This pragmatic randomized controlled trial evaluates whether Qiling Yiqi Tablets combined with antiretroviral therapy (ART) improves immune reconstitution in people with HIV who meet criteria for immune reconstitution failure and lung-spleen qi deficiency syndrome. Eligible participants are adults aged 18 to 60 years with HIV-1 infection, long-term viral suppression on ART, and persistently low CD4+ T-cell counts. A total of 240 participants will be randomized 1:1 to receive Qiling Yiqi Tablets plus ART or ART alone. Treatment lasts 48 weeks, followed by 48 weeks of follow-up. The primary outcomes are absolute CD4+ T-cell count and immune reconstitution response rate. Secondary outcomes include immune homeostasis markers, T-cell activation and Treg proportion, thymic output and inflammation-related markers, HIV RNA viral load, quality of life, clinical symptom scores, all-cause mortality, and safety.

This pragmatic randomized controlled trial evaluates whether Fuyang Jiedu Granules combined with antiretroviral therapy (ART) improves immune reconstitution in people with HIV who meet criteria for immune reconstitution failure and spleen-kidney yang deficiency syndrome. Eligible participants are adults aged 18 to 60 years with HIV-1 infection, long-term viral suppression on ART, and persistently low CD4+ T-cell counts. A total of 240 participants will be randomized 1:1 to receive Fuyang Jiedu Granules plus ART or ART alone. Treatment lasts 48 weeks, followed by 48 weeks of follow-up. The primary outcomes are absolute CD4+ T-cell count and immune reconstitution response rate. Secondary outcomes include immune homeostasis markers, T-cell activation and Treg proportion, thymic output and inflammation-related markers, HIV RNA viral load, quality of life, clinical symptom scores, all-cause mortality, and safety.

The study aims to better characterize intestinal tissue-resident memory T cells (TRM) in people living with HIV-1 receiving suppressive antiretroviral therapy (ART). TRM cells are key components of tissue immunity and may contribute to HIV-1 persistence within the intestinal mucosa, a major viral reservoir. The phenotypic, transcriptomic, and functional characteristics of intestinal CD4+ and CD8+ TRM cells, their susceptibility to HIV-1 infection, and their potential role as viral reservoirs will be investigated. Blood samples and additional colonic biopsies obtained during routine clinically indicated colonoscopy will be collected from HIV-1-infected participants and HIV-seronegative controls.

The purpose of the study is to evaluate the pharmacokinetics (PK), safety, tolerability, and acceptability of a long-acting injectable Cabotegravir and Rilpivirine in Virologically Suppressed Children Living with HIV-1, Two to Less Than 12 Years of Age

People with HIV experience earlier impairments in physical function compared to people in the general population. They also exhibit an earlier presentation and more rapid development of frailty, a multisystemic syndrome of aging characterized by reduced activity, fatigue, slowness, weakness, and weight loss. While exercise can improve physical function in people with HIV, it is less effective in doing so than in the general population and is difficult to sustain in the long-term. The goal of this clinical trial is to learn whether the medication tesamorelin will improve physical function and muscle health in adults with HIV when combined with exercise. Tesamorelin is a growth hormone-releasing hormone analogue that is FDA-approved to treat abdominal fat accumulation in people with HIV. While tesamorelin has also been shown to increase muscle mass and improve measures of muscle health, its effects on physical performance and muscle strength have not yet been evaluated. During a 24-week intervention phase, half of participants will be randomly assigned to receive tesamorelin and half of participants will be randomly assigned to receive placebo (a look-alike substance that contains no drug). All participants also will engage in a home-based exercise intervention supervised by an exercise coach. During a subsequent 24-week extension phase, individuals will be monitored off study drug and supervised exercise, and be encouraged to continue to exercise independently. The investigators will investigate effects of tesamorelin on physical function, muscle mass and quality, quality of life, and exercise adherence and self-efficacy. They also will evaluate whether effects of tesamorelin are maintained following treatment cessation. This study may identify an important strategy to improve how individuals aging with HIV function and feel with potential applications to other patient populations.

People living with HIV (PLWH) need to take antiretroviral therapy (ART) long-life. The development of new and more effective ART regimens has increased viral suppression and improved the recovery of immune function, leading to an extension of the lifespan of PLWH. However, antiretroviral drugs have short- and long-term side effects. In fact, ART has recently been reported as one of the significant factors associated with metabolic syndromes (obesity, liver disease, and factor). This insidious progression of long-term metabolic complications has become a new challenge for our clinics. Therefore, optimizing ART in the context of viral suppression is mandatory. In recent years, thanks to the availability of more potent drugs with a high genetic barrier, simplification strategies have been explored with various regimens containing fewer drugs for PLWH who are virologically suppressed on a standard three-drug regimen. Based on international guidelines, following the results of clinical trials, two-drug regimens are now recommended as pro-active switch strategies within preventive strategies to reduce morbidity in PLWH. Following the results of the ATALS-2M, FLAIR, and SOLAR studies, the long-acting parenteral regimen containing cabotegravir and rilpivirine (CAB+RPV), administered every 2 months, has been included in the guidelines as a pro-active switch strategy for maintaining virological suppression. Cabotegravir, a new integrase inhibitor (INI), has demonstrated high efficacy, excellent tolerability, and safety, with a higher-than-average genetic barrier. Rilpivirine is a non-nucloside reverse transcriptase inhibitor (NNRTI) with potent virological efficacy and a favorable safety profile compared to other NNRTIs. This type of strategy has several primary advantages: improve adherence, especially in complex PLWH, easier to integrate into daily activities, less likely to generate stigma and/or discrimination. Furthermore, intramuscular administration, bypassing intestinal metabolism, potentially reduces the severity of drug-drug interactions. In light of the growing attention to the metabolic impact of various antiretroviral therapy regimens and their associated adverse events, it is crucial to examine the tolerability of this injectable regimen as a medium- and long-term switching strategy. The results of the Phase 3 studies are based on populations with a short exposure to antiretroviral drugs, which may not be generalized to PLWH with a long history of ART, who represent the majority of patients in clinical practice in high-income countries. This study aims, in a clinical practice setting, to evaluate the cumulative probability of treatment discontinuation (TD) at 48 weeks in PLWH switching to the injectable LA CAB + RPV (LAI CAB + RPV) regimen from an oral regimen with rilpivirine/emtricitabine/tenofovir alafenamide fumarate (RPV + FTC + TAF).