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

Inclusion criteria

• Participants must meet all of the following criteria to be eligible for this study:
• Aged \>=18 years.
• 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.
• Established medical care outside NIH.
• Able to provide informed consent.
• Willing to allow samples to be stored for future research.
• Willing to allow genetic testing.
• Undergoing cART using recommended, alternative, or other regimens as defined by "Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV."
• 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).
• CD4 cell count \>=350 cells/microliter.
• Willing to interrupt ART for up to 90 days.
• 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:
• Active intercurrent illness or infection, including fever \>38 degrees Celsius.
• 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).
• Breastfeeding.
• 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.
• Undergoing ART that is incompatible with an ATI.
• Has undergone PET/CT within the last 6 months.
• History of poorly controlled diabetes that, in the judgement of the investigators, would prevent completion of PET/CT scan.
• Vaccination within the previous 4 weeks.
• History of ATI within the past 1 year.
• Has comorbid illness for which, in the judgment of the investigators, an ATI will represent elevated risk.
• Active opportunistic infection as defined by the Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV.
• Significant active substance abuse or psychiatric illness that may, in the judgment of the investigator, interfere with study visits or procedures.
• Allergy to planned anesthetic agents that are expected to be used. For local anesthetics, this is lidocaine. For sedation, this is midazolam and fentanyl.
• Currently undergoing chronic systemic steroid therapy (corticosteroid nasal spray or inhaler, topical steroid use, and hormone replacement are acceptable).
• Contraindication to use of IV contrast.
• History of developing keloids.
• 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.
• Active or chronic hepatitis B virus infection, with detectable hepatitis B surface antigen, hepatitis B virus DNA, or both.
• Active hepatitis C virus infection, with detectable virus RNA.
• History of HIV-associated dementia or progressive multifocal leukoencephalopathy.
• 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.
• 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.
• History of AIDS-defining illness according to CDC criteria within the past 3 years.
• Hepatic impairment: aminotransferase \>2.5 x the upper limit of normal or documented history of cirrhosis.
• Any condition that, in the judgment of the investigator, contraindicates participation in this study.