HIV and Tuberculosis Drug Interactions

Eligibility Details: - PARTICIPANT INCLUSION CRITERIA: Individuals must meet all of the following criteria to be eligible for study participation: 1. Ages 18-65 years. 2. Weight greater than or equal to 45 kg and less than or equal to 120 kg OR body mass index greater than or eqaul to 18.0 and < 30. 3. Judged to be healthy based on medical history, physical examination, vital signs, and clinical laboratory tests: liver function tests (AST, ALT, Tbili) less than or equal to upper limit of normal [ULN], SCr less than or equal to ULN, platelets (PLT) > 150,000/microL, hemoglobin (Hgb) > 13 g/dL (males); greater than or equal to 12g/dL (females), C-reactive protein (CRP) less than or equal to ULN, CK less than or equal to 2x ULN, fasting total cholesterol < 240 mg/dL, or fasting triglycerides < 240 mg/dL, urine glucose < grade 2 (per DAIDS AE table), urine protein < grade 2 (per DAIDS AE table). 4. Negative QuantiFERON-TB Gold test at screening. 5. HIV-negative, as determined by standard serologic assays for HIV infection. 6. No laboratory evidence of active or chronic hepatitis A, B, or C infection. 7. Willing to abstain from alcohol consumption throughout the study period. 8. Agrees to genetic testing and storage of specimens for future research. 9. Able to provide informed consent. 10. Negative serum or urine pregnancy test for females of child-bearing potential. 11. Participants must agree not to become pregnant or impregnate a partner for the duration of the study. The use of hormonal contraceptives will not be permitted. Study participants must use one of the following methods of birth control when engaging in sexual activities that can result in pregnancy, beginning at screening until the final study visit. 1. Male or female condom. 2. Diaphragm or cervical cap with a spermicide. 3. Intrauterine device without hormones. PARTICIPANT EXCLUSION CRITERIA: Individuals meeting any of the following criteria will be excluded from study participation: 1. Known hypersensitivity to TAF, TDF, INH, RPT, and other rifamycin analogues. 2. History or presence of any of the following: 1. Latent or active TB infection. 2. Gastrointestinal (GI) disease that is uncontrolled, requires daily treatment with medication, or would interfere with a participant s ability to absorb drugs (eg, diarrhea, pancreatitis, or peptic ulcer disease). 3. Renal impairment (chronic renal insufficiency of any chronic kidney disease stage, or acute renal failure not induced by drug therapy defined as eGFR < 90 mL/min or SCr > ULN). 4. Respiratory disease that is uncontrolled or requires daily treatment with medication (eg, asthma or chronic obstructive pulmonary disease). 5. Cardiovascular disease (eg, hypertension [systolic blood pressure > 140 mm Hg or diastolic blood pressure > 90 mm Hg], heart failure, or arrhythmia). 6. Metabolic disorders (eg, diabetes mellitus). 7. Hematologic or bleeding disorders (eg, anemia, hemophilia, serious/major bleeding events, menorrhagia [female participants]). 8. Immunologic disorders. 9. Hormonal or endocrine disorders. 10. Psychiatric illness that would interfere with their ability to comply with study procedures or that requires daily treatment with medication. 11. Seizure disorder, with the exception of childhood febrile seizures. 12. Any current or history of malignancy, with the exception of cutaneous basal cell carcinoma,non-invasive squamous cell carcinoma, or any other malignancies not requiring systemic therapy. 13. Current or history of osteopenia and osteoporosis. 3. Current participation in an ongoing investigational drug protocol or use of any investigational drug within 30 days (based on last dose received) prior to receipt of any study drugs. 4. Therapy with any prescription, over-the-counter (OTC), herbal, or holistic medications, including hormonal contraceptives by any route, within 5 half-lives of the agent prior to receipt of any study medications will not be permitted with the following exception: Intermittent or short-course therapy (<14 days) with prescription or OTC medications, herbals, or holistic medications within the screening period prior to starting study drugs may be permitted, and will be reviewed by investigators on a case-by-case basis for potential drug interactions. Receipt of influenza vaccination will be allowed prior to, during, and/or after the study. 5. Inability to obtain venous access for sample collection. 6. Inability to swallow whole capsules and/or tablets. 7. Pregnant or breastfeeding. 8. Drug use that may impair safety or adherence. 9. Use of nicotine-containing products, including cigarettes and chewing tobacco, nicotine patches, gum, electronic cigarettes, etc. 10. Organ or stem cell transplant recipient. 11. Uncorrected and persistent electrolyte abnormalities (eg, potassium, magnesium, and calcium). 12. Current alcohol use disorders (DSM-5 criteria). 13. Fasting total cholesterol > 240 mg/dL or fasting triglycerides > 240 mg/dL at screening. 14. Any condition that, in the opinion of the investigator, contraindicates participation in this study.