Imaging and biopsy of HIV-infected individuals during treatment interruption

Imaging and Biopsy of People With HIV-1 Undergoing Analytic Treatment Interruption

This study is testing how stopping HIV treatment affects the virus in the body by using imaging and tissue samples from people living with HIV.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (nih)
• Drugs / interventions: cART
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT05419024 on ClinicalTrials.gov

What this trial studies

This study aims to investigate the persistence of HIV-infected cells in individuals undergoing antiretroviral therapy (ART) by utilizing FDG-PET imaging and biopsies. Participants will be screened and assigned to either continue ART or undergo an analytic treatment interruption (ATI). The study will assess metabolic activity in lymphoid tissue to understand the mechanisms of HIV persistence and potential sites of replication. Tissue samples will be collected to further analyze the effects of ART interruption on HIV levels.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 years or older with HIV-1 who have maintained low viral loads on ART for at least three years.

Not a fit: Patients who are not on ART or have uncontrolled HIV levels may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved strategies for managing HIV and potentially finding a path towards a functional cure.

How similar studies have performed: While there have been studies exploring HIV persistence, this approach using FDG-PET imaging and biopsy during treatment interruption is relatively novel.

Eligibility criteria

* 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, topical steroid use, and hormone replacement 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 (e.g., atherosclerotic cardiovascular disease score \>20%) by a currently accepted risk calculator such as the 2023 AHA Predicting Risk of Cardiovascular Disease Events (PREVENT) or the 2018 ASCVD Risk Estimator Plus.
24. History of AIDS-defining illness according to CDC criteria within the past 3 years.
25. Hepatic impairment: aminotransferase \>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.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (RECRUITING)

Study contacts

• Principal investigator: Chuen-Yen C Lau, M.D. — National Cancer Institute (NCI)
• Study coordinator: Chuen-Yen C Lau, M.D.

Conditions: HIV, Human Immunodeficiency Virus, Antiretroviral Therapy, FDG-PET, Reservoir