HIV Clinical Trial
Official title:
Imaging and Biopsy of People With HIV-1 Undergoing Analytic Treatment Interruption
Background: Human immunodeficiency virus (HIV) infects CD4 T cells. There is no cure for HIV. People with HIV need to take daily medications called antiretroviral therapy (ART) to control their infection. ART stops HIV from infecting cells, but HIV does not go away. Some infected cells remain. If ART is stopped, then HIV levels will rise and infect more cells. Objective: To find where HIV-infected cells are located in the body, even when ART is keeping levels low. Eligibility: Adults aged 18 years or older who are undergoing ART for HIV infection. Design: Participants will be screened with a physical exam, including blood tests. They will be assigned to 1 of 2 groups: One group will stay on ART. They will have 2 study visits: the first 45 days after screening, and the second 12 to 16 weeks later. They will have a PET/CT scan at each visit. A substance called a tracer will be injected into their arm. They will lie still on a table that moves through a doughnut-shaped machine. This process takes up to 2 hours. The other group will stop ART for no more than 90 days. This group will have 3 PET/CT scans over 8 months. Once they stop ART, they will visit the clinic weekly for blood tests. After restarting ART, they will continue to visit the clinic weekly until their HIV level is safe. All participants will have small samples of tissue taken from lymph nodes. They may also opt to provide semen samples or vaginal fluid. They may have samples taken of bone marrow or the fluid inside their spinal column....
Status | Recruiting |
Enrollment | 50 |
Est. completion date | August 1, 2026 |
Est. primary completion date | August 1, 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 100 Years |
Eligibility | - INCLUSION CRITERIA: Participants must meet all of the following criteria to be eligible for this study: 1. Aged >=18 years. 2. People with HIV-1 documented using US Food and Drug Administration-approved screening and confirmatory or supplemental assays in Centers for Disease Control and Prevention (CDC)-recommended testing strategies. 3. Established medical care outside NIH. 4. Able to provide informed consent. 5. Willing to allow samples to be stored for future research. 6. Willing to allow genetic testing. 7. Undergoing cART using recommended, alternative, or other regimens as defined by Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. 8. Viral RNA <40 copies/mL plasma by conventional assay for at least 3 years (blips [transient increases within 6 weeks] of <200 copies/mL are allowable when succeeding viral levels return to <40 copies/mL on subsequent testing). 9. CD4 cell count >=350 cells/microliter. 10. Willing to interrupt ART for up to 90 days. 11. Willing to use a barrier method of contraception, such as condoms or dental dams, when engaging in sexual activity, or remain abstinent during ATI and after re-initiating ART until viral re-suppression is achieved, to prevent pregnancy and transmission of HIV. EXCLUSION CRITERIA: Participants who meet any of the following criteria will be excluded from this study: 1. Active intercurrent illness or infection, including fever >38 degrees Celsius. 2. Known history of initiating ART during the first year of infection with HIV. Participants will be considered to have initiated ART within 1 year of infection as defined by documented screening/confirmatory seroconversion (positive testing within one year of non-reactive HIV enzyme-linked immunosorbent assay). 3. Pregnant. 4. Breastfeeding. 5. Currently undergoing therapy with drugs that, in the judgment of the investigators, may interfere with biodistribution of FDG, including prednisolone, valproate carbamazepine, phenytoin, phenobarbital, and catecholamines. 6. Undergoing ART that is incompatible with an ATI. 7. Has undergone PET/CT within the last 6 months. 8. History of poorly controlled diabetes that, in the judgement of the investigators, would prevent completion of PET/CT scan. 9. Vaccination within the previous 4 weeks. 10. History of ATI within the past 1 year. 11. Has comorbid illness for which, in the judgment of the investigators, an ATI will represent elevated risk. 12. Active opportunistic infection as defined by the Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. 13. Significant active substance abuse or psychiatric illness that may, in the judgment of the investigator, interfere with study visits or procedures. 14. Allergy to planned anesthetic agents that are expected to be used. For local anesthetics, this is lidocaine. For sedation, this is midazolam and fentanyl. 15. Currently undergoing chronic systemic steroid therapy (corticosteroid nasal spray or inhaler and topical steroid use are acceptable). 16. Contraindication to use of IV contrast. 17. History of developing keloids. 18. Renal impairment: HIV-related kidney disease or estimated glomerular filtration rate (eGFR) CKD-EPI equation <60 mL/min/1.73 m^2. For individuals undergoing therapy with cobicistat or integrase strand inhibitors, GFR may be estimated using cystatin C or creatinine. 19. Active or chronic hepatitis B virus infection, with detectable hepatitis B surface antigen, hepatitis B virus DNA, or both. 20. Active hepatitis C virus infection, with detectable virus RNA. 21. History of HIV-associated dementia or progressive multifocal leukoencephalopathy. 22. Documented ARV drug resistance that, in the judgment of the investigator, would pose a risk of virologic failure should additional mutations develop during the study. 23. History of cardiovascular event or at high risk of an event (eg, atherosclerotic cardiovascular disease score >20%) (https://tools.acc.org/ascvd-risk-estimatorplus/#!/calculate/estimate/). 24. History of AIDS-defining illness according to CDC criteria within the past 3 years. 25. Hepatic impairment: alanine transaminase >2.5 X the upper limit of normal or documented history of cirrhosis. 26. Any condition that, in the judgment of the investigator, contraindicates participation in this study. |
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Cancer Institute (NCI) |
United States,
Lau CY, Adan MA, Maldarelli F. Why the HIV Reservoir Never Runs Dry: Clonal Expansion and the Characteristics of HIV-Infected Cells Challenge Strategies to Cure and Control HIV Infection. Viruses. 2021 Dec 14;13(12):2512. doi: 10.3390/v13122512. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Proportion of participants who have a 3 fold increase in HIV RNA levels in tissue sites identified by imaging as having increased SUV on FDG-PET as defined below | To evaluate if changes in glucose metabolism (as measured by FDG PET SUV) correlate with changes in levels of HIV RNA in lymphoid tissue before and after ATI. | Up to day 90 | |
Secondary | 1.Levels of HIV DNA and integration site analysis to assess clonal distribution at different biopsy sites, semen, vaginal swabs, and PBMCs. | 1.Characterize HIV populations (sequences) in sampled tissues, PBMCs, and plasma prior to and following ATI, and after treatment resumption. | Up to Month 6 | |
Secondary | 2.Correlation between regional and overall change in PET SUV with HIV DNA and RNA sequencing characteristics pre-ATI to post ATI | 2.Assess relationship between changes in PET SUV and genetic characteristics (eg, diversity, phylogenetics, and clonality) of HIV populations | Up to Month 6 | |
Secondary | 3.Cytokine and T-cell profiles during suppression and after ATI criteria for treatment resumption are met. | 3.Assess relationship between changes in soluble and cellular immune parameters and imaging findings during viral rebound | Up to Month 6 | |
Secondary | 4.HIV RNA and DNA sequence analyses for genetic studies and potential for replication competence. | 4.Estimate replication competence of HIV variants from different anatomic compartments (sample tissues, PBMCs, plasma, semen, vaginal secretions, and CSF) | Up to Month 6 | |
Secondary | 5.Correlation of HIV RNA levels and cytokine and T-cell profiles | 5.Compare kinetics of viral rebound after ATI with changes in immune activation markers. | Up to Month 6 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT06162897 -
Case Management Dyad
|
N/A | |
Completed |
NCT03999411 -
Smartphone Intervention for Smoking Cessation and Improving Adherence to Treatment Among HIV Patients
|
Phase 4 | |
Completed |
NCT02528773 -
Efficacy of ART to Interrupt HIV Transmission Networks
|
||
Active, not recruiting |
NCT05454839 -
Preferences for Services in a Patient's First Six Months on Antiretroviral Therapy for HIV in South Africa
|
||
Recruiting |
NCT05322629 -
Stepped Care to Optimize PrEP Effectiveness in Pregnant and Postpartum Women
|
N/A | |
Completed |
NCT02579135 -
Reducing HIV Risk Among Adolescents: Evaluating Project HEART
|
N/A | |
Active, not recruiting |
NCT01790373 -
Evaluating a Youth-Focused Economic Empowerment Approach to HIV Treatment Adherence
|
N/A | |
Not yet recruiting |
NCT06044792 -
The Influence of Primary HIV-1 Drug Resistance Mutations on Immune Reconstruction in PLWH
|
||
Completed |
NCT04039217 -
Antiretroviral Therapy (ART) Persistence in Different Body Compartments in HIV Negative MSM
|
Phase 4 | |
Active, not recruiting |
NCT04519970 -
Clinical Opportunities and Management to Exploit Biktarvy as Asynchronous Connection Key (COMEBACK)
|
N/A | |
Completed |
NCT04124536 -
Combination Partner HIV Testing Strategies for HIV-positive and HIV-negative Pregnant Women
|
N/A | |
Recruiting |
NCT05599581 -
Tu'Washindi RCT: Adolescent Girls in Kenya Taking Control of Their Health
|
N/A | |
Active, not recruiting |
NCT04588883 -
Strengthening Families Living With HIV in Kenya
|
N/A | |
Completed |
NCT02758093 -
Speed of Processing Training in Adults With HIV
|
N/A | |
Completed |
NCT02500446 -
Dolutegravir Impact on Residual Replication
|
Phase 4 | |
Completed |
NCT03805451 -
Life Steps for PrEP for Youth
|
N/A | |
Active, not recruiting |
NCT03902431 -
Translating the ABCS Into HIV Care
|
N/A | |
Completed |
NCT00729391 -
Women-Focused HIV Prevention in the Western Cape
|
Phase 2/Phase 3 | |
Recruiting |
NCT05736588 -
Elimisha HPV (Human Papillomavirus)
|
N/A | |
Recruiting |
NCT03589040 -
Darunavir and Rilpivirine Interactions With Etonogestrel Contraceptive Implant
|
Phase 2 |