Short-term Effects of Methamphetamine on Residual Latent HIV Disease Study

The most commonly used illicit stimulant in people with HIV (PWH) is methamphetamine (MA). Prior studies demonstrate strong evidence that MA promotes increased HIV transcription as well as immune dysregulation. A challenge in achieving worldwide HIV eradication is targeting specific marginalized populations who are most likely to benefit from an HIV cure but possess poorer immune responses. For this study, N = \~20 PWH virally-suppressed on antiretroviral therapy (ART) with no prior history of MA use disorder will be administered oral methamphetamine to determine the effects of short-term MA exposure on residual virus production, gene expression, and inflammation. Measures of MA exposure in urine and serum will then be associated with residual virus production, gene expression, cell surface immune marker protein expression, and systemic markers of inflammation. Thus, the proposed work will leverage a unique clinical trial design to generate advanced gene expression and immunologic data to identify potential novel targets for reversing HIV latency, reducing inflammation, and personalizing future therapies in PWH who use MA.

Inclusion Criteria: * Willing and able to provide written informed consent * Any gender, age ≥ 18 years \< 65 years * Laboratory confirmed documentation of HIV-1 infection. * Continuous therapy with a Department of Health and Human Services (DHHS) recommended/alternative combination ART for least 12 months (at least 3 agents) at study entry with no regimen changes in the preceding 12 weeks * Maintenance of undetectable plasma HIV-1 RNA ( \3 weeks) of systemic intravenous antibiotics. * Known anemia (HIV+ males Hct\< 34; females Hct\< 32) or contraindication to donating blood. * Screening hemoglobin below 12.5 g/dL * Poorly controlled hypertension or systolic blood pressure \> 140 on repeat measurement in the last 3 months, on more than one occasion. * Significant myocardial disease (e.g., current myocarditis or reduced left ventricular ejection fraction below the lower limit of normal) or diagnosed coronary artery disease. * History of cardiac arrhythmia that needs to be medically treated. * History of psychotic symptoms (e.g., hallucinations, delusional thinking) in the prior 3 months. * History of seizures, abnormal electroencephalogram or brain damage with significant persisting neurological deficit in the past 3 months or currently on anti- seizure medications * Significant respiratory disease requiring oxygen. * Exposure to any immunomodulatory drug (including maraviroc) in the 12 weeks prior to study * Prior or current use of experimental agents used with the intent to perturb the HIV-1 viral reservoir in the 12 weeks prior to study. * Participants of reproductive potential or breastfeeding. Women of childbearing potential must have a negative serum pregnancy test at screening. All participants of childbearing potential must agree to use a double-barrier method of contraception throughout the study period and up to 90 days after the last dose of MA. * Pregnancy. A serum pregnancy test will be performed. If this test is positive, the participant will not be allowed to enter the study since body changes occurring during pregnancy will alter the study results. * Recent vaccination within the last 2 weeks prior to study baseline visit.\* \*Note: Routine or standard of care vaccinations (such as SARS-CoV-2, influenza, pneumococcal, and meningococcal vaccinations) are allowed, but must be administered greater than 14 days prior to baseline study visit. For SARS-CoV-2 vaccination, the last dose must be administered at least 14 days prior to baseline study visit.