Exploring HIV Entry Blockade as a Pre-exposure Prophylaxis Strategy in Women

• Status: Completed
• Trial end date: 2015-05-01
• Target enrollment: 0
• Participant gender: Female

Summary

Pre-exposure prophylaxis (PrEP) is an HIV prevention strategy in which HIV medicines are used by a person before they are exposed to HIV in order to decrease his or her chance of getting infected. In this study, we will investigate a new PrEP strategy in women using a drug called maraviroc, a medicine used in the treatment of HIV infection called a CCR5 antagonist. We hypothesize that maraviroc could be a particularly good drug for PrEP because it achieves high concentrations in the genital tract in women and decreases the number of HIV-susceptible cells in the genital tract, and thus could potentially be dosed in more favorable ways than the current PrEP drugs.

In order to further evaluate this PrEP strategy, we plan to measure the amount of maraviroc in the blood and genital tract of HIV-negative healthy female volunteers before, during, and after they are given maraviroc dosed either in the standard (twice a day) or reduced (once a day) dose for 7 days compared with women who are not given maraviroc. We will also study immune cells from the blood and genital tract from these women to see if maravoric has an effect on these cells that would prevent them from becoming infected with HIV.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Emory University
• Treatments: Maraviroc

Criteria

Inclusion Criteria:

• Female sex, defined by sex at birth

• Age greater than or equal to 18 years

• Negative HIV serology at screening

• Normal menses (within 22-35 day intervals) for at least 3 cycles

• Intact uterus and cervix

• Normal chemistry and CBC panels at screening, including

• Absolute neutrophil count (ANC) greater than 750/mm3

• Hemoglobin greater than 10.0 g/dL

• Platelet count greater than 100,000/mm3

• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase less than 3 x upper limit of normal

• Total bilirubin less than 2.5 x upper limit of normal

• CrCl greater than or equal to 60 mL/min as estimated by the Cockcroft- Gault equation

• Negative hepatitis B surface antigen

• Willing to use condoms for the duration of the study and abstain from sexual intercourse for 48 hours before each genital tract sampling

• Able and willing to provide informed consent

Exclusion Criteria:

• Pregnancy (by clinical history or positive urine pregnancy test at screening)

• Breastfeeding

• Alcohol or substance use that, in the opinion of the study investigator, would interfere with the conduct of the study

• History of loop electrosurgical excision procedure (LEEP), conization, or cryosurgery

• Use of systemic hormonal contraception

• Orthostasis at screening, defined as systolic blood pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg within three minutes of standing.

• Known history of heart or liver disease

• Known history of any medical condition that would interfere with conduct of the study, in the opinion of the study investigator

• Symptoms of active vaginal infection at the time of screening, including new ulcerative genital lesions or purulent and/or foul-smelling vaginal discharge

• Visible ulcerative genital lesions or purulent vaginal discharge during speculum pelvic examination performed at the time of screening

• Concomitant use of medications that interact with maraviroc or known allergy to maraviroc