Vaccine and Infectious Disease Division

Modeling which gender benefits most from vaginal microbicides

Recent clinical trials of vaginal microbicides have shown promise at reducing risk of HIV transmission. These microbicides are topical gels or creams and provide an opportunity for women to control the method of protection, a major benefit in areas where they often lack the power to request other methods of safe sex. These areas also tend to have high rates of heterosexual HIV transmission.  Vaginal microbicides could have multiple benefits: they could prevent transmission to an uninfected individual, they could reduce the infectivity of an HIV-infected individual, and they could protect against other sexually transmitted diseases.  Conversely, long-term use by an infected individual could lead to resistant variants of HIV, thereby nullifying the protective effect of the treatment.  Most clinical trials simply report the number of infections prevented over time, which oversimplifies the complex interplay of these potential factors.  Mathematical modeling can be used to improve our determination of these various efficacies, to determine whether and how they provide benefit to each gender, and to model the effects of their long-term usage in various populations to determine whether the efficacies change over time.

VIDD staff scientist Dr. Dobromir Dimitrov and colleagues, including VIDD affiliate investigator Dr. Benoit Masse, modeled the influence of various parameters on outcomes and identified the main factors that could provide a protective advantage to one gender over the other in the model.  They demonstrated that there is a complex interplay between and within baseline assumptions and model parameters, including HIV acquisition risks per sexual act, the efficacy mechanism of the microbicide, rates of viral resistance mutations and the reversion rate for those presumably fitness-reducing mutations after transmission.  In particular, the choice of metrics used to access public health impact of biomedical interventions, such as the number of infections prevented or the ratio of those infections prevented by gender, is often influenced the gender distribution of benefits from a microbicide intervention, especially when different timeframes of prevention were assessed.  This modeling study shows that a thorough assessment of the power of vaginal microbicides to prevent HIV transmission requires comprehensive analyses beyond simple assessment of infections prevented over fixed periods of time.

Dimitrov DT, Boily MC, Baggaley RF, Masse B. Modeling the gender-specific impact of vaginal microbicides on HIV transmission. J Theor Biol. 2011 Nov 7;288:9-20.