Background: Vaginal microbicides are topical products being studied for their potential to reduce the risk of penile-vaginal human immunodeficiency virus (HIV) transmission. Because the sexual acts that lead to infection in effectiveness trials are unobserved, identification of an effective vaginal product may be unwittingly circumvented if adherence to product is poor or if participants acquire infection through nonvaginal routes of exposure.
Purpose: To model the impact of receptive anal intercourse (RAI) on the measured effectiveness of vaginal microbicides and the power of clinical trials.
Methods: A mathematical model is proposed for assessing effectiveness and power as a function of microbicide efficacy, the probability that the microbicide is used for vaginal acts of intercourse with exposure to HIV, the probability that an act of intercourse with exposure to HIV is rectal, and the ratio of transmission probabilities for rectal versus vaginal intercourse.
Results: The model demonstrated that a moderate frequency of RAI among vaginal microbicide trial participants is expected to substantially reduce study power; if 1 in 50 acts are rectal, and if the rectal transmission probability is 20-fold greater than that of vaginal intercourse, then power to detect an otherwise 40% effective product with a 160 endpoint trial is reduced from 90% to 56%. If 1 in 25 acts are rectal then power is only 34%.
Limitations: Accurate reports of adherence and rates of RAI are difficult to obtain, and precise HIV transmission probabilities are unknown. Hence the true impact of unprotected RAI on vaginal microbicide trials cannot be quantified with certainty.
Conclusions: Counseling against RAI should be provided to all vaginal microbicide trial participants irrespective of sexual history. Collection of accurate behavioral data on RAI during trials is essential to understand whether failure to demonstrate an effect might be attributed to RAI.