Vaginal Ring Adherence in Sub-Saharan Africa: Expulsion, Removal, and Perfect Use

Abstract

In sub-Saharan Africa, HIV incidence and prevalence remain disproportionately high among women. Vaginal rings (VRs) have been formulated for the delivery of antiretroviral-based microbicides, and their favorable safety and tolerability profiles reported in clinical studies. Although the concept of drug release through a VR has existed since 1970, and VRs have been marketed since 1992 for contraceptive or hormone replacement purposes, VR use as a microbicide delivery system is a novel application. This is the first study to evaluate VR adherence among African women in the context of its potential use as an HIV prevention method, to examine predictors of adherence, and to describe clinical or contextual reasons for VR removals or nonadherence. This was a randomized trial of the safety and acceptability of a placebo VR worn for 12 weeks in 170 HIV-negative, African women aged 18-35 in four clinic sites in South Africa and Tanzania. The findings suggest that adherence to VR use in the context of HIV prevention trials in these communities should be high, thereby enabling more accurate assessment of an active microbicide safety and efficacy.

Intravaginal ring eluting tenofovir disoproxil fumarate completely protects macaques from multiple vaginal simian-HIV challenges

“…Thus, it is reasonable to assume that it will be easier for women to adhere to long-duration IVR delivery systems compared with daily, episodic, or coitally dependent gels. This is supported by the fact that IVRs have seen excellent product demand and commercial success as a form of birth control in high-income countries and are gaining acceptance in low-income countries (7,29).…”

“…Simply put, if the course of protective antiretroviral levels does not match the kinetics of viral exposure, PrEP will not be highly effective. This motivates the development of long duration, drug delivery systems such as intravaginal rings (IVRs) that may overcome these limitations by facilitating adherence and providing less variation in mucosal drug levels (7,8).…”

Combination Pod-Intravaginal Ring Delivers Antiretroviral Agents for HIV Prophylaxis: Pharmacokinetic Evaluation in an Ovine Model

“…Topical delivery of ARV drugs using intravaginal rings (IVRs) is believed to improve adherence (18) while maintaining sustained mucosal microbicide levels independently of coitus and daily dosing (19). A recent phase 3, randomized, double-blind, placebo-controlled trial involving 2,629 African women evaluating a monthly IVR delivering the nonnucleoside HIV-1 reverse transcriptase inhibitor dapivirine (DPV) showed that this dosing modality can be effective at preventing HIV-1 infection (20).…”

Pharmacokinetics and Preliminary Safety Study of Pod-Intravaginal Rings Delivering Antiretroviral Combinations for HIV Prophylaxis in a Macaque Model

“…Controlled topical delivery of ARV drugs using intravaginal rings (IVRs) is thought to improve adherence (11) and to provide sustained mucosal levels independent of coitus and daily dosing (12). The delivery of two or more ARV drugs from conventional IVR designs involves significant technological and manufacturing hurdles.…”