Genital inflammation reduces efficacy of tenofovir gel against HIV in women

Genital inflammation in women substantially reduced the effectiveness of tenofovir gel in preventing HIV infection, according to findings published in Nature Medicine.

“HIV acquisition risk varies widely within a population and is dependent on behavioral and biological factors,” Lyle R. McKinnon, PhD, assistant professor of Medical Microbiology at the University of Manitoba, Canada, and colleagues wrote. “Younger women (< 25 years of age), for example, experience higher HIV incidence, likely owing to a combination of types and frequencies of sexual partnerships and biological factors, such as genital inflammation.”

McKinnon and colleagues wrote that in several trials, the effectiveness of pre-exposure prophylaxis (PrEP) was lowest among women aged younger than 25 years compared with any other group. Men who have sex with men who were highly adherent to oral PrEP were better protected against HIV infection than young women in one study.

“Case-control analyses of the three trials that have tested topical tenofovir in women showed that protection against HIV ranged from 50% to 60% if product adherence was high,” the researchers wrote. “These data suggest that adherence alone might not fully explain the incomplete efficacy of this product.”

The researchers performed a post hoc prospective analysis of 774 patients who participated in the Centre for the AIDS Program of Research In South Africa (CAPRISA) 004 study, a trial of topical tenofovir gel. McKinnon and colleagues measured concentrations of nine different proinflammatory cytokines from cervicovaginal lavages, and defined genital inflammation using a graduated cytokine store.

Tenofovir gel was 57% protective against HIV in women without genital inflammation, the researchers reported (95% CI, 7-80), but only 3% protective in women with genital inflammation (95% CI, –104 to 54).

Among highly adherent women, women without inflammation demonstrated 75% protection (95% CI, 25-92), whereas women with inflammation showed –10% protection (95% CI, –184 to 57).

“Inflammation is a major risk factor for HIV acquisition; reducing genital inflammation through treating its root causes or using anti-inflammatory agents might further optimize PrEP for women,” McKinnon and colleagues wrote. “Genital inflammation should be investigated as a potential effect modifier in trials for new PrEP products.” – by Andy Polhamus

Disclosures: McKinnon reports no relevant financial disclosures. One author holds a patent related to PrEP.