Clinical Research Directory

HIV-DNA and Risk of HIV-RNA Rebound After Sustained Suppression

Brief Summary: The vast majority of people with HIV (PWH) who adhere to antiretroviral therapy achieve sustained suppression of viral replication. Despite undetectable plasma HIV RNA, HIV DNA persists in latently infected cells, and individuals may differ in their vulnerability to future treatment failure. Total and intact HIV DNA levels in virologically suppressed PWH have recently attracted interest as potential markers of HIV reservoir size and composition, which may influence the risk of viral rebound, particularly following treatment simplification to regimens with potentially lower antiviral potency. To investigate the value of HIV DNA as a marker of future treatment vulnerability, this case-control study will collect blood samples retrospectively and prospectively from PWH who experience viral rebound after at least six months of sustained virological suppression (cases) and matched PWH who remain virologically suppressed over the corresponding period (controls). Matching will be based on age, sex, and duration of virological suppression. For each participant, one peripheral blood mononuclear cell (PBMC) sample and one plasma sample will be collected within a predefined window, starting at least six months after virological suppression is achieved and ending at least three months before viral rebound in cases or the corresponding reference time in controls. PBMCs will be used to quantify total and intact HIV DNA, while plasma will be analyzed for standard soluble inflammation markers. The study aims to determine whether higher total and/or intact HIV DNA levels predict subsequent virological failure and whether these measures are associated with systemic inflammation markers. Study Title: HIV-DNA and Risk of HIV-RNA Rebound After Sustained Suppression (VIROMARKERS WP3-HIV) Background \& Rationale: Although antiretroviral therapy (ART) achieves HIV-RNA viral load suppression below 50 copies/mL in over 95% of people living with HIV (PWH), the virus persists in reservoirs and cannot be fully eradicated. Total HIV-DNA is a well-established surrogate marker of the viral reservoir; however, it often overestimates the replication-competent reservoir. The Intact Proviral DNA Assay (IPDA) allows for the specific quantification of intact proviruses capable of replication. While total HIV-DNA and intact proviral DNA show promise as candidate biomarkers to predict the risk and timing of viral rebound, their clinical utility and predictive accuracy in routine patient profiling require consolidated clinical validation. Furthermore, persistent viral expression from the reservoir may trigger chronic immune activation and systemic inflammation despite sustained plasma viral suppression. Study Objectives:To establish a standardized platform across participating research sites for quantifying total and intact HIV-DNA using stored blood, peripheral blood mononuclear cell (PBMC), or purified CD4+ T-cell samples. To evaluate the association between total/intact HIV-DNA levels and the risk of HIV-RNA viral rebound in PWH under sustained virological suppression. To assess the correlation between total/intact HIV-DNA levels and key systemic inflammatory biomarkers during suppressive ART. Study Design \& Methodology: This is an international, retrospective, and prospective observational case-control study conducted across well-characterized European cohorts of PWH. The study will analyze a minimum of 300 participants, comprising 100 "cases" who experienced virological rebound and 200 matched "controls" who maintained full virological suppression. Cases: PWH under suppressive therapy who experienced virological rebound (defined as two consecutive viral loads \>200 copies/mL or a single viral load \>1,000 copies/mL followed by an ART change). Controls: PWH matched 2:1 to cases based on age, sex, cohort, and duration of HIV-RNA suppression, who maintained HIV-RNA ≤50 copies/mL over the same follow-up timeframe. Key Eligibility Criteria. Inclusion Criteria: Adults (≥18 years) with confirmed HIV diagnosis enrolled in a cohort with regular viral load monitoring (≥2 values/year); sustained HIV-RNA ≤50 copies/mL for \>6 months under modern ART (started after 2012); availability of stored PBMC, whole blood, and plasma samples collected while suppressed; and at least 2 additional viral load measurements post-baseline. Exclusion Criteria: Active Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) coinfection. Study Procedures \& Biomarker Testing: Genomic Testing: stored PBMC or whole blood samples collected during viral suppression (at least 3 months prior to rebound for cases) will be analyzed central-site for total HIV-DNA and intact proviral DNA (IPDA). Proteomic Testing: plasma samples collected at matching timepoints will undergo proteomic evaluation to measure markers of inflammation/immune activation.

HIV-1 Non-group M in Cameroon : Study of Genotypic and Phylogenetic Diversity (OBSOCAM)

The aim of the study is to study the genotypic characteristics of HIV-1 non-M circulating in the whole Cameroon and their genetic evolution.

HPV Vaccine Therapy in Reducing High-Grade Cervical Lesions in Patients With HIV and HPV

This randomized phase III trial studies how well human papillomavirus (HPV) vaccine therapy works in reducing high-grade cervical lesions in patients with human immunodeficiency virus (HIV) and HPV. Vaccines made from HPV peptides or antigens may help the body build an effective immune response to kill the HPV virus and prevent cervical lesions from developing or coming back after being removed.

Reaching Persons With HIV Who Are Out of Care Through Expedited Access to Long-Acting Injectable Antiretroviral Therapy - The RELAI Study

Purpose: The purpose of this study is to evaluate the acceptability of field-based long acting cabotegravir/rilpivirine (LA-CAB/RPV) among people with HIV (PWH) who are out of care. Participants: 40 adult men and women living with HIV will be enrolled Procedures (methods): This is a pilot, open-label study to evaluate the acceptability, feasibility, and virologic impact of field-based LA-CAB-RPV for PWH who are out of care. This study will enroll 40 participants who accept field-based LA-CAB-RPV, targeting \>50% who reside in rural or semi-rural counties. Participants will be followed for 7 months, with duration of follow-up selected based on the FDA approved every 2 month LA-CAB-RPV injection schedule for virally suppressed patients, aligning with the 5th injection for an every two-month cycle

Technology-based Training Tool for PHAT Life

Youth under age 18 involved in the criminal justice system are disproportionately minorities \& affected by substance abuse, mental illness, \& HIV/STI. Most young offenders are released on community supervision without the STI, mental health, or substance use screening, diagnosis, \& treatment afforded detained youth, despite similar rates of risk behavior. Their long-term trajectory is poor, costs to society are high, \& lasting effects on community well-being \& individual employment prospects are profound. Altering this trajectory is a public health priority. Preventing HIV Among Teens (PHAT) Life is an evidence-based program that meets the need in juvenile justice to address youths' co-morbid health problems. The next step in ensuring that this decade-long line of research produces actual, real-world improvements in the lives of probation youth is to develop a PHAT Life training strategy that is effective, cost-effective, \& sustainable within juvenile justice settings. The private/public collaboration between ORBIS \& UIC will leverage existing resources \& competencies to create a commercially viable technology-based training tool for PHAT Life with great potential for sustainability \& cost-effectiveness. This Phase II uses a formative process to refine, enhance \& complete the technology-based training tool to include: (a) an interactive multimedia web browser \& mobile application, (b) dynamic multimedia presentations \& interactive queries, (c) video examples of mock intervention delivery, (d) audio narration along with scripted language, (e) brief quizzes to ensure comprehension \& knowledge acquisition, (f) opportunities to "learn more" by clicking on tabs for supplemental information, (g) targeted referrals to appendix materials, (h) games to promote engagement, \& (i) other adaptations based on Phase I feedback. The proposed technology-based training tool should be highly sustainable, because it (a) relies on "indigenous" personnel to deliver the intervention, (b) is likely to prove cost-effective since it will utilize a technology that can deliver training at scale, \& (c) will improve fidelity by leveraging technology to provide consistent training experiences to para-professionals. The training tool will be evaluated via a 2-arm RCT with 130 individuals who work with justice-involved youth. Trainees will receive the technology-based training tool.

Functional Interval Training for Veterans Exercising Through Telehealth.

Most Veterans living with HIV are 50 years of age or older and can expect to live more than 20 years longer with HIV medication. However, despite this success, Veterans living with HIV are more likely to have age-related diseases and loss of fitness and muscle that place them at increased risk for disability. This is a major priority for the VHA, the largest provider of HIV care in the United States. The goal of this study is to test a circuit exercise program in Veterans living with HIV that is designed to slowdown the aging process. The exercise program will be widely available by Video Teleconferencing (VTEL) and does not require stationary exercise equipment, making it widely accessible. This research will help reach the goal for Veterans to preserve their quality of life and ability to function independently. Novel findings will strengthen strategies to maintain life-long fitness through a personalized exercise prescription.

DOR/ISL in Pediatric Participants With HIV-1, <18 Years of Age and ≥ 35 kg

This is a phase 2 study of the pharmacokinetics, safety, and efficacy of oral doravirine/islatravir (100 mg/0.25 mg) \[MK-8591A\] in pediatric participants with human immunodeficiency virus type 1 (HIV-1) infection who are virologically suppressed or treatment-naive. The Base Study will last from Day 1 to Week 96. At Week 96, participants will be given the option to participate in an optional Study Extension and receive DOR/ISL until Week 240 or until it becomes commercially accessible, whichever is first.

Therapy Adapted for High Risk and Low Risk HIV-Associated Anal Cancer

This phase II trial studies the side effects of chemotherapy and intensity modulated radiation therapy in treating patients with low-risk HIV-associated anal cancer, and nivolumab after standard of care chemotherapy and radiation therapy in treating patients with high-risk HIV-associated anal cancer. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Chemotherapy drugs, such as mitomycin, fluorouracil, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with radiation therapy may kill more tumor cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving nivolumab after standard of care chemotherapy and radiation therapy may help reduce the risk of the tumor coming back.

Gene Therapy and Combination Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma

This pilot clinical trial studies gene therapy following combination chemotherapy in treating patients with acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma. Placing genes that have been shown in the laboratory to inhibit the growth and spread of the immunodeficiency virus (HIV) into the patient's peripheral blood stem cells may improve the body's ability to fight HIV. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving gene therapy after combination chemotherapy may improve the body's ability to fight HIV and AIDS-related non-Hodgkin lymphoma.

Enhancing Cervical Cancer Screening and Treatment in Women Living With HIV in Kenya, the ENHANCE LINKAge Trial

Background In sub-Saharan Africa (SSA), human papillomavirus (HPV) and HIV create a dual burden of disease that causes significant morbidity and mortality in the form of cervical cancer (CC). Women living with HIV (WLWH) have a six-fold higher risk of developing precancerous lesions that persist and progress to CC, which is the leading cause of cancer mortality among women in Kenya. Significant support from the Go Further campaign, represented by donors such as the President's Emergency Plan for AIDS Relief (PEPFAR), the George W. Bush Institute, UNAIDS, Merck, and Roche, to integrate CC screening into HIV clinics represents an exceptional opportunity to scale CC impact across SSA, but only if implementation science evidence is available to inform strategy. Currently, the impact of Go Further has been undermined by fractured linkages to care and insensitive screening methods; in Kenya, less than 2% of WLWH screened have received appropriate treatment. Implementation science studies are needed to better understand and surmount barriers to integrated care in publicly funded HIV clinics. Broad objective This study seeks to explore and innovate strategies to overcome patient-, provider-, and system-level barriers to implementing CC screening and referral guidelines, link WLWH who require further diagnostic testing and/or treatment with effective and accessible care, and document services for accountability and quality improvement. In this proposal, our team will apply our extensive implementation science expertise and partnerships with Kenya Ministry of Health (MOH) to adapt and test evidence-based strategies (e.g., HPV self-testing, care navigators, and the WEMA mHealth app \[tested and scaled in Tanzania\]) that address key multi-level barriers identified through a formative, stakeholder-engaged research phase. Methodology Using the EPIS framework to guide our project, we will: Aim 1a), Explore (engage a multi-disciplinary stakeholder advisory board to co-design the intervention package and prioritize implementation strategies that align with local capacity, opportunities, and motivations; Aim 1b), Prepare (develop tools and strengthen capacity at clinics to implement the strategies; Aim 2), Implement and evaluate the package of implementation strategies via a cluster-randomized stepped wedge trial in 9 clinics (assessing implementation \[provision of CC screening with HPV self-testing\] and effectiveness \[proportion of HPVpositive WLWH who receive subsequent diagnostic triage and/or treatment\] over months 0-12; and Aim 3), assess Sustainability (costs, cost-effectiveness, and transfer of delivery from study to local staff over months 13-18. Significance of the study The overall goal of this study is to employ rigorous empirical methods to adapt and test implementation strategies that expand the scope of HIV care to screen for and treat early precancerous CC lesions in a sustainable, scalable way. Through partnering with Kenya's MOH, this project will have critical institutional support and dissemination capability, and will directly inform public health practice and policy.

Very Early Intensive Treatment of Infants Living With HIV to Achieve HIV Remission

The study will explore the effects of early intensive antiretroviral therapy (ART) with or without a broadly neutralizing antibody (bNAb) on achieving HIV remission (HIV RNA below the limit of detection of the assay) among infants living with HIV.

Gene Therapy After Frontline Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma

This pilot clinical trial studies gene therapy after frontline chemotherapy in treating patients with acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). Placing genes for anti-human immunodeficiency virus (HIV) ribonucleic acid (RNA) into stem/progenitor cells may make the body build an immune response to AIDS. Giving the chemotherapy drug busulfan before gene therapy can help gene-modified cells engraft and work better.

An Adaptive Platform Trial for Evaluation of Novel Treatment Regimens in Children and Adolescents With HIV in Africa

The goal of the CHAPAS-5 clinical trial is to find out how well different HIV treatments work in children and young people (from 4 weeks up to under 15 years old) living with HIV, including those starting treatment for the first time and those whose current treatment is not working well. The study aims to learn whether newer or different combinations of medicines can better control the virus, be safer, and be easier to take. The main questions it aims to answer are: * Can these treatments help children stay alive and keep their HIV virus at very low levels (viral load below 400) after 48 weeks? * Which treatment options are most effective, safest, and easiest for children and their carers to use? Researchers will compare different treatment groups to see if some medicines work better than others. Participants will be given one of several HIV treatment combinations (all already used in care), and these will be compared to see if they lead to: * Better control of HIV * Fewer side effects * Improved quality of life Participants will: * Be randomly assigned (like flipping a coin by computer) to one suitable HIV treatment * Take their HIV medication every day as prescribed * Attend clinic visits over about 1-2 years At these visits, they will: * Have blood tests to check HIV levels and general health * Have health check-ups (e.g. weight, symptoms, side effects) * Answer simple questionnaires about: * How easy the treatment is to take * Mood, sleep, and wellbeing * Quality of life * Receive support to help them take their medication regularly Some participants may also take part in optional extra studies (for example, to understand how the drugs work in the body). Overall, this study aims to identify the best HIV treatments for children and young people, so future care can be more effective, safer, and easier to follow.

Strengthening, Guidance, Health, Empowerment

The goal of this interventional study is to describe the care pathway following the use of an innovative home self-sampling method for the screening of six sexually transmitted infections (STIs) among sex workers met during physical or virtual outreach activities conducted by the ROSELA programme of Médecins du Monde in Montpellier and the surrounding area. The main questions it aims to answer are: * How many people are offered STI self-sampling, receive a self-sampling kit, and return the collected samples for laboratory testing * What proportion of participants are recontacted and attend a consultation following the screening results Participants will receive a self-sampling kit allowing them to collect samples at home or at a place of their choice and complete a questionnaire covering socio-demographic information and information related to their sex work activity.

Safety, Tolerability, and Efficacy of IL-15 Superagonist (N-803) With and Without Combination Broadly Neutralizing Antibodies to Induce HIV-1 Control During Analytic Treatment Interruption

The purpose of this study is to evaluate the safety, tolerability, and efficacy of N-803, an IL-15 superagonist, with or without combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).

Screening Algorithms for Cervical and Anal High-Grade Squamous Intraepithelial Lesions in People With HIV in Mexico and Puerto Rico

This clinical trial aims to find what different tests work best to find high-grade squamous intraepithelial lesions (HSIL) in the cervix or anus in patients living with human immunodeficiency virus (HIV). Patients with HIV are at high risk of becoming infected with human papillomavirus (HPV) in the cervix or anus where it can turn into cancer over several years. HPV causes changes to the cervix and anus, known as HSIL. This means that there is an area of abnormal tissue on the top layers of the cervix or anus. It is considered cervical or anal cancer if the abnormality spreads down into the layers of tissue below the top. If found early, many cases of HSIL can be treated before turning into cancer. Screening for cervical or anal cancer detection or HSIL associated with HPV may result in earlier treatment, if necessary, for patients living with HIV.

Expanding HOPE Liver

This is a prospective, multicenter clinical study. The objective is to determine whether a liver transplant from a deceased donor with HIV is associated with an increased risk of opportunistic infection and cancer. Adults with Human Immunodeficiency Virus (HIV) in need of a liver or simultaneous liver-kidney (SLK) transplant who meet study-specified criteria will be offered enrollment in the study. The analytic plan includes an observational cohort of liver and SLK transplant recipients from prior HOPE in Action studies.

Impact of Behavior Modification Interventions and Lung Cancer Screening on Smoking Cessation in People Living With HIV: A Feasibility Study

This clinical trial evaluates the usefulness of using a smartphone-based HIV-specific smoking cessation intervention at the time of lung cancer screening in helping people living with HIV quit smoking. Positively Smoke Free - Mobile may help patients with HIV quit smoking.

Detection of Specific Metabolic Signatures by Nuclear Magnetic Resonance or Metabolomic NMR in Correlation With Markers of Inflammation or Immune Activation and the Risk of Developing Neurocognitive Disorders - Longitudinal Retrospective Study Nested in the ANRS12225 PEDIACAM III Cohort

The ANRS12225 PEDIACAM III cohort involves a cohort of young adolescents living with HIV placed early (median: 4 months) on antiretroviral therapy (ART) and living without HIV monitored in Cameroon. This cohort follows the evolution of the psychomotor development of children living with HIV by mother-to-child transmission under antiretroviral treatment (ART) since birth as part of the cohort between 2016-2017 in children aged 4-9 years (ANRS12322 -PEDIACAMDEV) using the KABC II (Kaufman Assessment Battery for Children II). Despite early ART, children with HIV had significantly lower cognitive scores than uninfected children. Multiple neurodevelopmental studies have shown that intrauterine infection or even low- noise inflammation could impact the development of a child's brain allowing cognitive impairment to appear later in life. Other studies have also shown that metabolic defects could be the cause of chronic inflammation and immune activation. Admittedly, many studies have been carried out in cohorts of HIV-positive adults as well as HIV-positive children on neurological disorders. But very few have made the link between metabolism, inflammation, immune activation and neurocognitive disorders in infants and children in countries with limited resources. The ANRS12225 PEDIACAM III cohort offers the unique opportunity in Africa to carry out a study in a population of children living with HIV matched with a population of children living without HIV born to HIV + mothers and children living without HIV born to HIV-infected mothers in follow-up longitudinal. To explore this area, this pilot project will make it possible to assess the relevance of a cutting-edge, highthroughput technique, metabolomic NMR (Nuclear magnetic resonance), to quantify metabolites and lipoproteins in plasma and study their predictive value for the appearance of Neurodevelopmental disorders in children of different groups of the ANRS12225 PEDIACAM III cohort. It is intended to be completed within a short period (18 months) in order to be continued by more ambitious projects

Baricitinib Curative Repression of HIV-1

This study is being done to test whether a drug called baricitinib, which blocks specific causes of inflammation, affects HIV-1 viral rebound and viral load levels after HIV treatment is discontinued. Researchers will test the effects of continuing baricitinib in people with HIV before and after discontinuing their antiretroviral therapy. This drug is approved by the Food and Drug Administration (FDA) for other diseases; it is not approved for the treatment of HIV-1. The study team will also investigate any side effects associated with the drug.

Acceptability, Quality of Care, Patient Satisfaction, and Cost-effectiveness of Monitoring Provided by Nurses or Physicians for People Using HIV Pre-exposure Prophylaxis

Assess the quality of care and the satisfaction of patients and caregivers when the monitoring of people on HIV pre-exposure prophylaxis (PrEP) is provided by nurses instead of physicians

Optimization of Antiretroviral Therapy in Patients With AIDS-Related Lymphoma

The goal of this clinical trial is to evaluate the efficacy and safety of different antiretroviral therapy (ART) strategies in adults with AIDS-related lymphoma (ARL) receiving anti-lymphoma treatment. The main questions it aims to answer are: Does long-acting injectable ART, including albuvirtide (ABT) or long-acting cabotegravir/rilpivirine (CAB/RPV), improve virological suppression compared with oral ART during anti-lymphoma treatment? Do different ART strategies differ in immune recovery, virological failure, low-level viremia, and safety in patients with ARL? Researchers will compare three treatment strategies-oral ART alone, oral ART plus long-acting albuvirtide (ABT), and long-acting cabotegravir/rilpivirine (CAB/RPV)-to determine whether long-acting injectable ART provides better virological control and comparable safety during lymphoma treatment. Participants will: Receive one of three ART strategies according to their clinical condition and treatment preference while receiving standard anti-lymphoma therapy. Attend scheduled study visits at baseline and Weeks 4, 8, 12, 24, 36, and 48. Undergo plasma HIV-1 RNA testing, CD4+ T-cell count measurement, laboratory assessments, and safety evaluations throughout the 48-week follow-up period. Be monitored for virological suppression, immune recovery, adverse events, and lymphoma-related clinical outcomes.

MAPS PrEP Van Study

For this study the investigators aim to see if giving participants an oral HIV prevention medication on a medical van, is a good option of care for individuals who inject drugs and/or are sexually active and therefore at a higher risk of contracting HIV.

HIV Disclosure and Medication Adherence, a Pilot Study

The investigators believe that disclosure of HIV status could influence medication adherence. If disclosure leads to social support, adherence could be improved. This study purpose is to assess correlation between disclosure and medication adherence, and to describe people whose HIV status has been disclosed to.