Adherence and its measurement in phase 2/3 microbicide trials.

Adherence optimization and measurement have emerged as critically challenging issues for clinical trials of topical microbicides. Although microbicide trials have routinely collected adherence data, their utilization in trial design, implementation, and interpretation has been inconsistent. Drawing on data-driven presentations from several focused meetings, this paper synthesizes lessons from past microbicide trials and provides recommendations for future trials of microbicide and other HIV prevention technologies. First, it describes four purposes for adherence data collection, with particular attention to intention-to-treat versus adherence-adjusted analyses for determining effectiveness. Second, the microbicide field's experiences with adherence measures and data collection modes are discussed, including the strengths and weaknesses of various options and approaches for improving measurement. Then, several approaches to optimizing trial participants' adherence are presented. The paper concludes with a set of recommendations for immediate use or further research.

Microbicide preference among young women in California.

BACKGROUND: Microbicides for HIV/sexually transmitted infection (STI) prevention are still in development. Microbicide acceptability studies have thus focused on soliciting input from individuals about hypothetical products using traditional epidemiological and behavioral research methodologies. Here, we integrate a well-established market research method, conjoint analysis, with more traditional epidemiological and behavioral research to examine potential users' preferences for different microbicide formulations. METHODS: Focus group discussions (n = 67) were held with a diverse population of young men and women (aged 18-32 years) from Northern California. Then, young women participated in structured surveys (n = 321) that included a conjoint study, a methodology not yet used in microbicide acceptability. The main outcome measures were intentions for different microbicide formulations, inferred preferences for microbicide characteristics, and self-reported risk factors for HIV, other STIs, and pregnancy. RESULTS: Risk of STIs and unwanted pregnancies is a concern within this population. Participants' responses suggest that the ideal microbicide would (1) offer protection from pregnancy, HIV, STIs, and vaginal infections, (2) offer as much protection as condoms, (3) allow insertion up to 8 hours prior to sexual activity, (4) be available over the counter (OTC), (5) be inserted with an applicator, and (6) have only slight leakage not requiring a panty liner. The average predicted purchase probability for this ideal microbicide was 69%. CONCLUSIONS: Our findings help illustrate microbicide product preferences and demand among young women in California, and the methodological approach should lend itself to other populations as well as during clinical trials when understanding product use and nonuse is critical.

Microbicide acceptability research: current approaches and future directions.

With growing recognition of the potential value of microbicides for HIV/STI prevention, the importance of the acceptability of this brand-new technology has been widely acknowledged. We review the current body of microbicide acceptability research, characterize the limitations in assessment approaches, and suggest strategies for improvement. Electronic databases and abstracts of recent meetings were searched for acceptability data regarding vaginal and rectal products that may be used for HIV prevention. Of the 61 studies reviewed, more than half assessed acceptability based primarily on the description of a hypothetical microbicide, or with the demonstration of a spermicide or lubricant. Physical characteristics of microbicidal products, their effects after insertion, and their effects on sensation during intercourse (for both partners) were the dimensions most frequently assessed (measured in 77%, 49% and 49% of studies, respectively). Attention to the social context of use was inadequate. As acceptability is likely to be a key determinant in the use-effectiveness of microbicides, in-depth understanding of the social processes that shape microbicide acceptability across diverse populations will become increasingly valuable. This includes exploring the effects that sexual partners, health care providers, and key opinion leaders have on the acceptability of microbicides among women and men, including youth and people living with HIV. Future research will benefit from studies of the acceptability of other contraceptive-barrier methods (especially the female condom), use of an agreed-upon operationalization of acceptability, use of acceptability assessments within clinical trials, expansion of measurement domains, and assessment of changes in perceptions of acceptability and use over time. Failure to understand the key factors associated with microbicide acceptability is likely to hinder the adoption and continued use of products that are effective in preventing HIV infection.

Topical microbicides for disease prevention: status and challenges.

As the human immunodeficiency virus and sexually transmitted disease epidemics advance relentlessly, it is clear that an armamentarium of therapeutic and preventive methods will be essential to their containment. Topical microbicides--self-administered prophylactic agents applied to the vagina or rectum in various formulations--could be a crucial addition to that necessary armamentarium. This article provides an update on the dramatically broadening array of approaches being pursued in microbicide research and development and identifies critical challenges to progress.

Microbicides from a regulatory perspective.

OBJECTIVE: To provide researchers, product sponsors, drug regulators, and funding organizations with a convenient reference regarding regulatory guidance for microbicide development and licensure. METHODS: WHO and other leading agencies in the microbicide field sponsored a series of technical consultations over the past decade that engaged a wide range of international experts in regional settings of primary relevance for microbicide development, testing, and eventual use. This article summarizes the results of those consultations against the ever-changing background of HIV prevention. RESULTS: These efforts have significantly clarified the scientific basis for developing regulatory guidance for microbicide development and licensure. CONCLUSION: The technical consultations organised by WHO and others have substantially expanded regulatory perspectives about the development and testing of topical microbicides for preventing the sexual transmission of HIV and other STIs.