Qualitative Consumer Research on Acceptance of Long-Acting Pre-Exposure Prophylaxis Products Among Men Having Sex with Men and Medical Practitioners in the United States.

Pre-exposure prophylaxis (PrEP) with oral Truvada® prevents HIV infection. However, the adherence to pill taking required for efficacy has sparked interest in developing new antiretroviral delivery systems that decrease such demands. Long-acting formulations, such as injections and implants, represent promising options that require less frequent adherence. It is important, however, that development of these new modalities be driven by understanding of the value seen in them by target users to maximize their uptake. To identify the key product features that impact user acceptance, we used a three-phase marketing research approach. In this study, we describe the results of the first-phase, qualitative focus group research performed in Chicago and San Francisco that explored subjective perceptions of oral versus alternative PrEP modalities among men having sex with men (MSM) and medical practitioners caring for MSM. Data revealed that potential value in long-acting PrEP lies more in simplifying the lives of users rather than in making them more confident in their adherence. The results provide an important guidance for designing and promoting these future long-acting products to enhance their contribution to increasing the current limited uptake of PrEP that will better stem the HIV epidemic.

Assessment of topical microbicides to prevent HIV-1 transmission: concepts, testing, lessons learned.

The development of topically applied products capable of preventing vaginal and rectal transmission of HIV-1 has been on-going for nearly 20 years. Despite this, only one clinical trial has demonstrated protection against sexual transmission of HIV-1 in women. This review covers the development of microbicides, also referred to as topical pre-exposure prophylaxis (PrEP), through three stages. The first stage focused on nonspecific agents, including surfactants such as nonoxynol-9 (N-9), to prevent HIV-1 transmission. Unfortunately, N-9 enhanced susceptibility to sexual transmission of HIV-1 when evaluated for efficacy. Soon thereafter, other nonspecific agents (polyanions) were quickly moved into large efficacy trials. Due to a lack of coordination among investigators and funders, a large investment was made in a class of compounds shown ultimately to be ineffective, although poor adherence may have contributed to these findings. The second stage involved the assessment of the antiretroviral drug tenofovir, formulated as a vaginal gel, which was found to be modestly effective in a Phase IIb trial (CAPRISA-004) when dosed in a coitally-dependent manner. In another Phase IIb trial, VOICE (MTN-003), tenofovir gel was found to be ineffective when dosed once-daily in a coitally-independent manner. Based on pharmacokinetic data, it was concluded the participants were poorly adherent to this dosing regimen, leading to a lack of efficacy. Tenofovir gel is currently in a Phase III safety and efficacy trial in South Africa (FACTS-001), using the coitally-dependent dosing regimen employed in CAPRISA-004. We are now in the third stage of microbicide research. The antiretroviral drug dapivirine is currently in two Phase III safety and efficacy studies formulated as a vaginal ring. It is hoped that the once-monthly dosing regimen will lead to higher adherence than found in the VOICE study. It is now clear that product adherence could be the greatest challenge to demonstrating topical (and to a similar extent oral) PrEP. Novel dosage forms should play a role in creating products that women will use correctly.

Advances in microbicide vaginal rings.

Vaginal ring devices capable of providing sustained/controlled release of incorporated actives are already marketed for steroidal contraception and estrogen replacement therapy. In recent years, there has been considerable interest in developing similar ring devices for the administration of microbicidal compounds to prevent vaginal HIV transmission. Intended to be worn continuously, such coitally independent microbicide rings are being developed to maintain effective vaginal microbicide concentrations over many weeks or months, thereby overcoming issues around timing of product application, user compliance and acceptability associated with more conventional semi-solid formulations. In this article, an overview of vaginal ring technologies is presented, followed by a review of recent advances and issues pertaining to their application for the delivery of HIV microbicides. This article forms part of a special supplement on presentations covering intravaginal rings, based on the symposium "Trends in Microbicide Formulations", held on 25 and 26 January 2010, Arlington, VA.