Women design their own vaginal microbicide trial: Suggestions on how to improve adherence from former participants of HIV prevention trials

Low adherence in vaginal microbicide clinical trials for HIV prevention has impeded interpretation of trial results and hindered evaluation of potentially efficacious HIV prevention gels. Understanding the underlying reasons why women join trials and their barriers to product use can support identification of ways to improve adherence and its reporting. Eight focus group discussion workshops were conducted with 46 former microbicide trial participants in Durban, South Africa and Mwanza, Tanzania. Participants provided feedback on why women join trials, the barriers to using study gel and reporting adherence accurately, and how clinical trial design can be improved to support better adherence and its reporting. Women join microbicide trials for a number of important reasons such as healthcare and financial reimbursement. Fear of adverse effects from the investigational product was the most important reason why participants reported not using the gel. The key reason for inaccurate reporting of gel use was fear of removal from the trial. Participants made concrete suggestions for improving microbicide trial design such as applicator use testing and real time feedback, improving education to participants about how trials answer their research questions, and improving transparency and clarity about study procedures. Participants also gave feedback on an innovative trial design with a non-randomised arm. Identifying HIV prevention products for women requires better understanding of the lives of women asked to join these trials, and application of that understanding to microbicide trial design. This study has demonstrated that participants and research teams can work collaboratively to design clinical trials that meet needs of both the research and of participants.

Tenofovir Hot-Melt Granulation using Gelucire® to Develop Sustained-Release Vaginal Systems for Weekly Protection against Sexual Transmission of HIV

Hot-melt granulation is a technique used to obtain granules by dispersing a drug in polymers at a high temperature. Tenofovir, an antiretroviral drug with proven activity as a vaginal microbicide, was dispersed in melted Gelucire® (or a mixture of different Gelucire®) to obtain drug-loaded granules. Studies performed on the granules proved that the drug is not altered in the hot-melt granulation process. The granules obtained were included in a matrix formed by the hydrophilic polymers hydroxypropylmethylcellulose and chitosan to obtain vaginal tablets that combine different mechanisms of controlled release: The Gelucire® needs to soften to allow the release of the Tenofovir, and the hydrophilic polymers must form a gel so the drug can diffuse through it. The studies performed with the tablets were swelling behavior, Tenofovir release, and ex vivo mucoadhesion. The tablets containing granules obtained with Tenofovir and Gelucire® 43/01 in a ratio of 1:2 in a matrix formed by hydroxypropylmethylcellulose and chitosan in a ratio of 1.9:1 were selected as the optimal formulation, since they release Tenofovir in a sustained manner over 216h and remain attached to the vaginal mucosa throughout. A weekly administration of these tablets would therefore offer women protection against the sexual transmission of HIV.

Ensuring Health Care Providers Have Comprehensive Communication Tools for Future Microbicide Introduction in Kenya: A Formative Research Study

As the field of HIV prevention advances and new antiretroviral (ARV)-based prevention products are developed, health care providers will play a critical role in promoting or limiting new product use. To provide evidence-based communication supporting potential product roll-out, we developed and assessed a suite of vaginal microbicide communication materials tailored to various Kenyan audiences. However, our materials could potentially be adapted for use with other ARV-based prevention products and settings. For health care providers, we developed three sets of materials: informational brochures, wall charts, and a counseling flip chart. Trained research assistants conducted 24 in-depth interviews with providers from a range of health facilities in Nairobi and Nakuru, Kenya. Interviews assessed providers’ current HIV counseling practices for women in different types of sexual relationships, attitudes toward vaginal microbicide gel, and thoughts on the content and usefulness of the microbicide communication materials; priority was given to the counseling flip chart. Interviews also included hypothetical counseling scenarios to assess providers’ potential to appropriately use materials and adapt their counseling techniques. Microbicide communication materials were well received and effective in educating providers about microbicides and in helping them provide appropriate counseling for hypothetical scenarios involving women in different sexual contexts.