Protocol No: ECCT/15/09/01 Date of Protocol: 23-06-2015

Study Title:

Effects of contraceptive ring on vaginal microbiota, HIV shedding and local immunity


Study Objectives:

Primary Objective:

To assess potential benefits associated with both cyclic (use for 3 weeks, remove for 1 week, as defined in the package insert) and continuous (use for 4 weeks, then replace) CVR use among women (both HIV-negative and HIV-positive) with BV at enrollment (and thus at high risk for BV persistence and recurrence).

Secondary objectives:

  1. To determine the effect of the CVR on clinically defined incidence of BV, the vaginal microbiome and rates of adverse events with CVR use.
  2. To assess the acceptability of the CVR to men who are sex partners of study participants.
  3. To assess acceptability and preference for contraceptive type at study end.


Laymans Summary:

The need for contraceptive options in women at risk for HIV acquisition has taken on urgency with evidence indicating that systemic hormonal contraception (primarily injectable, long-acting progestin) may increase women’s risk of HIV acquisition and transmission to male sex partners.1 Lack of other contraceptive options, especially for women at highest risk of HIV in Sub-Saharan Africa, is a critical barrier to progress towards optimizing women’s reproductive health. While intrauterine devices (IUDs) are an option, implementation of delivery has been slow. The use of a contraceptive vaginal ring (CVR) has been explored and reported on in several Sub-Saharan African countries, and its acceptability in general is excellent.2 A commonly used CVR in the United States is the NuvaRing. Moreover, the format of drug delivery through the form of a vaginal ring is also being intensely explored with the use of antiretroviral agents (dapivirine, tenofovir) as a means of topical, female-controlled HIV prevention, and formulation work with several antiretroviral drugs for sustained delivery with the NuvaRing format is underway.3 Such “multicomponent prevention” has become a major focus for scientists, advocates, and funders alike.


Abstract of Study:

Our objective is to study effects of a contraceptive vaginal ring (CVR) containing estrogen and progesterone (NuvaRing) on vaginal bacteria, HIV shedding, and local immunity in women. We will build on data that support a favorable effect of CVR on vaginal bacteria. Bacterial vaginosis (BV) is found in >50% of women in sub-Saharan Africa. BV significantly increases risk of HIV acquisition in, and HIV transmission to male partners from, HIV-infected women, genital HIV shedding, and viral set point in infected male partners. Pregnancy is also an independent risk for HIV acquisition and transmission. Contraception comprises critical biomedical prevention for women with or at risk for HIV. Systemic depot progesterone—commonly used throughout Africa—may independently increase risk of HIV acquisition and transmission. Hormonal interventions preventing unintended pregnancy and promoting a protective vaginal microenvironment could synergistically reduce HIV risk especially combined with topical antiretrovirals (ARV). We hypothesize NuvaRing use may contribute to reduction in BV, pregnancy prevention, and decreased rates of HIV shedding in HIV-infected women. Sustained vaginal delivery of contraceptive and ARV PrEP as “multicomponent prevention” is a major focus for scientists but effects on the vaginal environment need careful definition before broad implementation.

Aim 1: Determine effect of CVR on vaginal bacteria, including incident/persistent BV. Show whether sustained local hormone delivery promotes desirable lactobacilli, and thus reduces risk of BV, in women with and without HIV.

Aim 2. Define the soluble mucosal host immune response and endocervical immune cell populations with CVR. Determine if shifts in vaginal bacteria anticipated to occur with CVR will be accompanied by favorable changes in the lower genital tract, including restoration of protective mediators decreased with BV.

Aim 3. In HIV-infected women, determine effect of CVR on genital HIV shedding. HIV-infected women not on ART at enrollment will have endocervical swabs collected for HIV RNA quantification.

Study Site and Population

This study will be conducted at the Thika Partners Study Clinic located in Thika, Kenya. We will enroll approximately 120 women with bacterial vaginosis (BV) based on clinical criteria and a minimum of 75 male sex partners.