Sex and the single microbicide
Richard Jefferys, TAG
The levels and distribution of an anti-HIV microbicide in the genital tract are likely to be critical factors in determining potential efficacy.
Up until now, research studies have typically assessed microbicide levels in sexually abstinent women, which neglects to consider the potential impact of sexual activity. A new study in PLoS One looks at whether the physical act of sex and the introduction of semen into the genital tract affects the microbcide candidate 0.5% PRO 2000 gel. The study was conducted and completed before the recent announcement that 0.5% PRO 2000 gel had failed to show efficacy in preventing HIV infection in a large randomized clinical trial.
The results showed that 0.5% PRO 2000 gel levels were significantly lower after sex, and this correlated with a reduced ability of cervicovaginal lavage (CVL) from gel-treated women to inhibit HIV and HSV-2 in vitro. It was noted, however, that lower gel concentrations did not fully explain the reduction in antiretroviral activity; additional experiments revealed that seminal plasma also had an independent effect.
The researchers acknowledge that their study has limitations, including a small sample size and a single-dose approach that may underestimate microbicide levels compared to repeat dosing. Nevertheless, they suggest that “the current paradigm of microbicide development should be modified to include postcoital sampling following single and repeated dosing with both active and placebo products and should be expanded to include both CVL and biopsies to more fully define the pharmacokinetics and pharmacodynamics of lead candidates prior to embarking on large-scale efficacy trials.”
Ref: Keller MJ et al. Postcoital bioavailability and antiviral activity of 0.5% PRO 2000 gel: implications for future microbicide clinical trials. PLoS ONE 5(1): e8781. doi:10.1371/journal.pone.0008781.