Dose-Proportionality and Intra-Individual Variability of Intracellular TFV-DP and FTC-TP in Healthy Volunteers

Exclusion Criteria

• •At screening::
• •* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 1.5 X the site laboratory ULN (upper limit of normal)
• •* Hemoglobin less than 10.0 g/dL
• •* Platelet count less than 100,000/mm3
• •* Serum phosphate level below site laboratory LLN (lower limit of normal)
• •* INR or aPTT greater than site laboratory ULN
• •* Other safety tests (bicarbonate (HCO3), potassium (K), chloride (Cl), sodium (Na), calcium (Ca), fasting glucose) with results outside of the laboratories reference range
• •* 1+ or greater protein on urine dipstick testing
• •* 1+ or greater glucose on urine dipstick testing
• •Culture-confirmed urinary tract infection
• •Co-enrollment in any other HIV interventional research study (excluding behavioral only interventions) or prior enrollment in the active arm of a HIV vaccine trial.
• •Clinically apparent or patient report of active skin disorders including: rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, and pustular rash.
• •Women who are pregnant or breastfeeding.
• •One or more reactive HIV rapid test results at screening or enrollment, even if HIV infection is not confirmed.
• •Positive hepatitis B surface antigen (HBsAg) test.
• •Excessive use of alcohol (more than 4 drinks a day on a regular basis).
• •Interleukin therapy; medications with significant nephrotoxic potential, including but not limited to amphotericin B, aminoglycosides, cidofovir, foscarnet and systemic chemotherapy; and medications that may inhibit or compete for elimination via active renal tubular secretion (including but not limited to probenecid).
• •Participants with a history of having a gastrectomy, colostomy, ileostomy, or any other procedure altering the gastrointestinal tract or drug absorption.
• •Intensive sampling cohort only:
• •* A positive test for syphilis, gonorrhea, or Chlamydia
• •* A positive test for HSV-2 (individuals with active lesions only)
• •* Findings consistent with bacterial vaginosis, vaginal candidiasis, or trichomonas (women only)
• •* History of STI within 3 months prior to enrollment
• •* Medications that prolong clotting time (e.g., warfarin, heparin, clopidogrel classes.)
• •* Abnormalities of the colorectal mucosa, or significant colorectal symptom(s), which in the opinion of the clinician represents a contraindication to biopsy (including but not limited to presence of any unresolved injury, infectious or inflammatory condition of the local mucosa, and presence of symptomatic external hemorrhoids).
• •* Clinically apparent pelvic exam finding (observed by study staff) of genital lesions, erythema, edema or any other abnormal physical or pelvic exam finding that, in the opinion of the investigator or designee, would contraindicate study participation.
• •* Women who have had cervical procedures (conization, LEEP procedure, cryosurgery) within the previous 6 months.
• •* Spermicide as a method for contraception within last 30 days
• •Any other reason or condition that in the judgment of the investigator, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.