Pharmacokinetics of Tenofovir, Emtricitabine, Maraviroc, and Raltegravir in Cervical, Vaginal, and Rectal Tissues and Secretions

Exclusion Criteria

• •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including documented drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing).
• •Subjects with a history of hysterectomy
• •Subjects who are pregnant, possibly pregnant, or lactating
• •Subjects with a presence of vaginal discharge or genital bleeding at screening
• •History of febrile illness within five days prior to first dose.
• •Any condition possibly affecting drug absorption (eg, gastrectomy).
• •A positive urine drug screen.
• •A positive result for HIV.
• •Active Hepatitis B infection as determined by positive Hepatitis B surface antigen (HbsAg) or Hepatitis B core antibody (HBcAb) tests (in the absence of HBsAb).
• •Active Hepatitis C infection as defined by anti-hepatitis C virus serology (determined by multi-antigen EIA) and detectable Hepatitis C viral RNA.
• •A positive test for syphilis, gonorrhea, Chlamydia, or trichomonas at screening or symptomatic bacterial vaginosis.
• •Any laboratory chemistry or hematology result Grade 2 or greater according to the DAIDS Laboratory Grading Tables.
• •Treatment with an investigational drug within 4 months preceding the first dose of trial medication.
• •History of regular alcohol consumption exceeding 14 drinks (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of spirits) per week.
• •Participation in a clinical trial involving vaginal or rectal biopsies within 12 months preceding the first dose of trial medication.
• •Use of prescription or nonprescription drugs, vitamins, and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of trial medication. As an exception, systemic hormonal methods of contraception can be continued.
• •Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing
• •History of sensitivity to heparin or heparin-induced thrombocytopenia
• •Any vaccination within 30 days of study entry
• •Allergy to lidocaine or Mohl's solution
• •Allergy to latex
• •Abnormal pap smear in the past 12 months
• •Any degree of ectopy or abnormality evident during the pelvic exam at screening
• •Any condition which, in the opinion of the investigator, is likely to interfere with follow-up or ability to take the study medication appropriately.
• •Unwilling or unable to comply with the following dietary restriction in regard to study drug administration:
• •Subjects must abstain from all food and drink (except water) at least 4 hours prior to any safety laboratory evaluations
• •Subjects must abstain from all food and drink (except water) at last 8 hours prior to the start of pharmacokinetic sample collections
• •Subjects will not be allowed to eat or drink grapefruit containing products from 7 days prior to the first dose of trial medication until collection of the final pharmacokinetic blood sample. While confined, the total daily nutritional composition will be approximately 50% carbohydrate, 35% fat and 15% protein, and the daily caloric intake per subject should not exceed approximately 3200 kcal.
• •Subjects will be required to consume only a clear liquids diet the night before the rectal biopsy procedure and until the procedure has been completed