December 13, 2011

CONRAD to Initiate Phase I Study to Assess the Effect of Contraception on Markers of Vaginal Immunity


Arlington, VA – CONRAD is pleased to announce the initiation of a study to examine the effects of two hormonal contraceptive methods on markers of mucosal immunity. Hormonal contraceptives, particularly long lasting methods such as Depo-Provera, are a key element of family planning in the developing world, where risk of HIV is also the greatest.  A recent study of the use of hormonal contraceptives and risk of HIV-1 transmission conducted by the Partners in Prevention HSV/HIV Transmission Study Team illustrated the importance of better understanding the effects of hormonal contraceptives and the risk of HIV-1 acquisition. 

This prospective open-label parallel cohort study will enroll 72 HIV-uninfected women aged 18-50 at low risk for sexually transmitted infections (STIs) at three sites to include the Eastern Virginia Medical School, PROFAMILIA in the Dominican Republic and the University of Pittsburgh School of Medicine.   Participants will select either Depo-Provera® or a combined oral contraceptive to use for 3 months. The study will also assess the effect of the methods and the menstrual cycle on the pharmacokinetics (PK) and pharmacodynamics (PD) of tenofovir (TFV) 1% vaginal gel. TFV gel will be administered in a modified BAT regimen in which participants insert the gel vaginally 1 hour before intercourse and 1 hour after intercourse.   Specimens will be collected approximately 4 or 12 hours after intercourse, as determined by randomization.

Vaginal specimens will be collected before starting contraception: once in the follicular phase of the menstrual cycle (after TFV gel) and twice in the luteal phase (with and without TFV gel). Samples will also be collected after initiation of contraception, once at 6 weeks without TFV gel and once at 10 weeks following TFV gel. Concentrations of TFV and its active metabolite, TFV-diphosphate, will be assessed in blood and genital tract specimens. Biopsies will be collected for immune cell activation, histology, and HIV-1 infectivity. CVL supernatants will be tested for anti-HIV and anti-HSV activity and soluble immune markers, and immune cells in the cell pellet will be characterized.

CONRAD has long been involved in gathering evidence on the effect of hormonal contraception on vaginal tissue.  In 1999, CONRAD published a study in which 16 women were followed for three months after their first injection of Depo-Provera. The vaginal epithelium was thicker in the follicular phase of the menstrual cycle than the luteal phase, but there was no difference between the luteal phase and after Depo-Provera administration. Previous studies in monkeys showed dramatic thinning after administration of progesterone implants, Depo-Provera, and Norplant II.

The health risks of pregnancy and HIV acquisition must be weighed against the use of hormonal contraception and while this Phase I study will not answer all outstanding questions, it will serve to provide more crucial data to the field to prevent HIV and STIs.