Early Metabolic Effects of Antiretroviral Drugs in Healthy volUnteers: a Phase 2 Randomized Study

* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: * Aged 18 to 55 years. * Able to provide informed consent. * Willing to allow samples and data to be stored and shared for future research. * Agrees to use a barrier method of contraception or abstain from sexual activity starting at screening though the end of study participation. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: * Current infection with HIV or hepatitis A, B, or C. * Body mass index (BMI) \<18.5 kg/m\^2 or \>30.0 kg/m\^2. * Weight change \>5% in the past 6 months. * History of or current cardiovascular disease such as congestive heart failure, heart block, or clinically relevant abnormal ECG as determined by investigators. * History of or current liver disease or alanine transaminase serum level \>2x upper limit of normal. * History of or current kidney disease or renal insufficiency, or estimated creatinine clearance \<=80 mL/min (Modification of Diet in Renal Disease equation). * Current cancer or history of cancer within 5 years of screening, with the exception of squamous cell carcinoma or basal cell carcinoma that is localized and does not require systemic therapy. * History of bariatric surgery. * Diabetes mellitus as defined by a prior diagnosis or a hemoglobin A1c of \>6.4 percent on screening labs. * Fasting serum glucose \>126 mg/dL. * History of or current hypo- or hyper-thyroid or abnormal TSH, except minor deviations deemed to be of no clinical significance by the investigator. * History of chronic obstructive pulmonary disease. * Psychological conditions by self-report, such as (but not limited to) clinical depression, or bipolar disorders, which would be incompatible with safe and successful participation in this study. * Pregnancy or within 1 year post-partum. * Breastfeeding. * Blood pressure \>140/90 mm Hg or current antihypertensive therapy. * Hemoglobin that is either 10 percent below the lower limit or 10 percent above the upper limit of the normal range for the Clinical Center Laboratory (acceptable ranges: females 10.08-17.27 g/dL, males 12.33-19.25 g/dL). * History of illicit drug, opioid, or alcohol abuse within the last 5 years; current use of illicit drugs or opioids (by history) or excessive alcohol (CAGE assessment score \>=2). * Current use of the following prescription or over-the-counter medications and supplements: * Carbamazepine * Oxcarbazepine * Phenobarbital * Phenytoin * Primidone * Rifabutin * Rifampin * Rifapentine * St. John's wort (Hypericum perforatum) * Cation-containing antacids or laxatives * Sucralfate * Buffered medications * Oral calcium, iron, magnesium, or zinc supplements, including multivitamins containing these polyvalent cations * Dalfampridine * Metformin * Dofetilide * Thyroid medications * Corticosteroids * Weight loss medications, including prescription drugs (eg, semaglutide and tirzepatide) and over-the-counter diet pills * Use of TAF, TDF, and/or FTC for the purpose of HIV PrEP or in a research study within the past 6 months. * Any history of exposure to cabotegravir or lenacapavir (eg, as HIV PrEP or as a participant in a research study for these drugs). * Current use of prescription or nonprescriptive medications that may have interactions with study drugs or confound the study measurements as determined by the investigators. * History of adverse or allergic reactions to the study drugs. * Daily caffeine intake \>500 mg (about 4 cups of coffee). * Current smoker or user of tobacco products. * A change in the participant's diet and/or exercise regimen in the past 3 months or during the timeframe of the study period that, in the opinion of the investigator, would compromise the integrity of the data. * High-risk sexual activity as determined by the investigators, and/or inability or unwillingness to use barrier contraception during the protocol. * Any other condition, medication, or dietary pattern that, in the opinion of the investigators, increases risk to the participant, prevents the participant from complying with study procedures, prevents the participant from completing the study, or interferes with the interpretation of study results.