Methodological issues in microbicide research and development

Abstract

A variety of research designs are useful in microbicide research. These designs include the individual-level RCT for determining microbicide effectiveness, the community intervention trial for assessing the impact of microbicide introduction into specific communities, cohort studies for examining microbicide use patterns under 'natural' conditions where a woman decides whether or not to use a microbicide, and sequential behavioral and disease surveillance surveys for assessing whether microbicide introduction is associated with HIV control in large populations. Ethical issues are critical in microbicide research. One prominent issue is the need to promote condom use in all treatment and control groups in microbicide studies; if we must do so, what intensity level of condom promotion is appropriate? A related issue is whether an intense condom promotion run-in phase can be used to screen into a microbicide trial only those women with poor condom adherence during the run-in phase? Also, is it ethical to conduct studies employing hierarchical counseling messages where some of the methods (e.g. microbicides) are of unproven effectiveness in preventing HIV? Microbicide effectiveness for HIV prevention will be influenced by population characteristics. For example, microbicide effectiveness will vary according to microbicide use. We can expect microbicide use to be lower in non-sex worker populations than in sex workers. Likewise, if microbicides are used for pregnancy prevention in addition to disease prevention, microbicide use may be lower in women using highly effective contraception. Microbicide effectiveness for HIV prevention may also be influenced by the prevalence of other sexually transmitted infections in a population. For these reasons it is important to conduct effectiveness research in those populations which will ultimately be targeted for microbicide interventions. In addition to exploring microbicide use among women with differing types of sex partners (i.e. commercial, regular, irregular) it will be important to address other behavioral issues in microbicide research. These include the effect of microbicide use on use of the male condom, microbicide use by pregnant women, women seeking to become pregnant, and women using highly effective contraception, and microbicide use by HIV-infected women. Also, akin to other barrier methods, we need to understand how to accurately measure microbicide use. Because microbicides will neither be 100% effective nor appropriate for all women, it will be important to add effective microbicides to the arsenal of physical and chemical barriers. Thus, current prevention efforts focusing on male condom and female condom use should continue. Likewise, it is important to continue research on the effectiveness of vaginal devices including female condoms, the diaphragm and cervical caps for HIV prevention.