Abstract and Introduction
A trio of studies on pre-exposure prophylaxis demonstrates proof-of-principle in heterosexual populations but highlights the need for more data from women.
Pre-exposure prophylaxis (PrEP) has been shown to be efficacious among men who have sex with men (MSM; JW AIDS Clin Care Nov 23 2010). This week, the New England Journal of Medicine published the results of three trials of PrEP among heterosexual populations in Africa:
Partners-PrEP, in which researchers tested oral tenofovir alone and oral tenofovir/FTC among 4747 heterosexual, HIV-serodiscordant couples
TDF2, in which researchers tested oral tenofovir/FTC among 1219 heterosexual men and women
FEM-PrEP, in which researchers tested oral tenofovir/FTC among 2120 heterosexual women
In all three trials, HIV-negative individuals were randomized to receive daily oral PrEP or placebo, along with comprehensive HIV prevention services, and were assessed monthly for HIV infection and clinical events. The primary endpoint was HIV prevention efficacy (the proportion of individuals who acquired HIV infection in the PrEP group compared with the placebo group).
The efficacy results were decidedly mixed (see table). In the Partners PrEP trial, PrEP was efficacious both in the overall population and among both men and women; the efficacy and safety of tenofovir alone and tenofovir/FTC were not significantly different. In the TDF2 trial, PrEP was efficacious in the overall population, but the study did not have sufficient power to demonstrate a statistically significant effect among women. Finally, in the FEM-PrEP trial, which involved only women, PrEP completely lacked efficacy.
In all three trials, adherence was relatively high (>80%) when measured by pill count and returned pill bottles. However, all these studies, as well as the iPrEx study among MSM, demonstrated low rates of detectable drug in plasma samples taken from seroconverters.
Treatment-emergent resistance was rare in the trials, occurring in only four participants (all in the FEM-PrEP study). The TDF2 study demonstrated a statistically significant but clinically ambiguous decline in bone-mineral density among those receiving tenofovir/FTC. In all three studies, researchers noted a decrease in sexual-risk behavior during follow-up.
AIDS Clinical Care © 2012 Massachusetts Medical Society