HIV Prevention trials
Apples and oranges? Interpreting success in HIV prevention trials
Heise LL, Watts C, Foss A, Trussell J, Vickerman P, Hayes R, McCormack S. Contraception. 2011 Jan;83(1):10-5
In the last decade, several large-scale clinical trials evaluating the efficacy of novel HIV prevention products have been completed, and eight are currently underway or about to be reported. Little attention has been given in the literature to the level of protection sufficient to warrant introduction, and there is concern that using the term "efficacy" to describe the effect of user-controlled methods such as microbicides may mislead policymakers. The authors reviewed how the fields of family planning, vaccine science, and mathematical modelling understand and use the terms efficacy and effectiveness, and explore with simple mathematical models how trial results of user-controlled products relate to common understandings of these terms. Each field brings different assumptions, a different evidence base, and different expectations to interpretations of efficacy and effectiveness - a reality that could cloud informed assessment of emerging data. When making judgments on the utility of new health technologies, it is important to use standards that yield appropriate comparisons for the innovation and that take into account the local epidemic and available alternatives.
Editors’ note: Deciding how good is good enough for a new HIV prevention technology to be worth introducing in your setting depends on a number of factors, including the risk of HIV infection—but it also depends on how randomised controlled trial findings are understood and whether a method is user-controlled or provider-controlled. The term ‘efficacy’ is used most frequently in reporting vaccine trial results where it measures the biological effect of a vaccine since there is objective evidence of whether a vaccine dose has been administered or not. Similarly, male circumcision, a one-time surgical procedure, is considered after three trials to be 50-60% efficacious in reducing HIV risk in heterosexual men. The term ‘efficacy’ has been used recently referring to the protection against HIV seen in the iPrEx chemoprevention trial among men who have sex with men who were in the active arm of the study and had detectable drug levels. To further complicate matters, trials measure protection achieved over time while modellers use ‘per-sex-act efficacy’ in modelling the potential impact of introducing a new prevention modality. However, most HIV prevention trial results report effectiveness, a combined measure of the biological efficacy of a product and its pattern of use in the trial. With respect to recently reported oral and topical pre-exposure prophylaxis trial results, it is evident that designing effective strategies to improve pill-taking behaviour or gel use, in addition to correct and consistent use of condoms, will be a key consideration, along with cost, demand, viral resistance, acceptability, incremental benefits, etc. in influencing policy makers decisions to add chemoprevention to their programming.