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Tenofovir gel fails to prevent HIV infection in women
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SEATTLE — Pericoital vaginal tenofovir 1% gel once again was found to be ineffective at preventing HIV acquisition among women, according to data from the FACTS 001 trial presented at CROI 2015.
“The results are very disappointing,” Helen Rees, MD, executive director of the Wits Reproductive Health and HIV Institute, University of Witwatersrand in Johannesburg, South Africa, said during her presentation. “Tenofovir gel has demonstrated a reduction in HIV acquisition in a proof of concept phase II2 trial, but there are now two phase 3 trials showing no benefit.”
Rees and colleagues evaluated the gel among HIV-negative, sexually active women aged 18 to 30 years. The study included 2,059 women who were randomly assigned to tenofovir gel or placebo. Baseline characteristics between the two groups were similar. The modified intent-to-treat analysis included 1,015 women in the tenofovir arm and 1,014 in the placebo arm, after participants were excluded for HIV-positivity at enrollment or not having a follow-up visit after randomization.
Helen Rees
There were 61 HIV infections over 1,515 person-years of follow-up among women in the tenofovir arm and 62 HIV infections over 1,521 person-years of follow-up in the placebo arm. The incidence rate was the same in both: 4.0 per 100 person-years, an incidence rate ratio of 1.0 (95% CI, 0.7-1.4).
The researchers estimated the use of the gels by dividing the number of returned used applicators by the number of reported sex acts and cutting that in half. By these estimates, participants in both arms used the gel in 50% to 60% of sex acts per month, on average.
In a pre-specified, case-cohort substudy in the tenofovir arm, the researchers measured tenofovir levels in cervicovaginal lavage samples taken quarterly. This study included 56 seroconverters and 158 controls. Among the 1,075 samples, 64% had any tenofovir detected. Tenofovir was detected at all quarterly visits for 22% of the women and never detected in 13% of the women. In an adjusted model, detection of tenofovir was associated with 52% protection (HR = 0.48; 95% CI, 0.23 – 0.97).
“HIV prevention in women is a major public health priority,” Rees said. “Pericoital vaginal tenofovir 1% gel was safe, but not effective in preventing HIV acquisition in this population. There is an urgent need for a range of HIV prevention options for young women, which may be easier to integrate into their lives.” – by Emily Shafer
Reference:
Rees H, et al. Abstract 26LB. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 23-26, 2015; Seattle.
Disclosure: Rees reports no relevant disclosures.
Perspective
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Jeanne Marrazzo, MD, MPH
Tenofovir gel just does not seem to be a generalizable, appropriate intervention for HIV prevention in women. There is clearly a subset of women, seen in both the VOICE and FACTS studies, who did use the product consistently. In the VOICE study, we could detect it in the blood of some women who used the gel. But when you look at the intention to treat populations and the whole group, it just is not right for these women, regardless of the biomedical evidence, which is incredibly strong.
Even in oral PrEP studies, you can chart the incredibly direct relationship between adherence and efficacy. It’s fair and safe to say that the lack of efficacy is almost certainly related to the lack of adherence. There may be other issues in the genital tract that are contributing, but there is clearly a relationship with adherence, which was seen even in the oral PrEP studies.
There is certainly work to be done with gel products. The most exciting potential area is probably for rectal use, as a lubricant for MSM. There is a tenofovir product in phase 1 studies now that is designed for rectal use. The question is whether we know enough about that product, the molecule, the safety and its efficacy overall to move that forward into an efficacy study. It could be that if the men in those studies take up the product in the way that they take up oral PrEP, we will be pleasantly surprised.
In terms of where it’s going in women, there are still unanswered questions. There was a significant protection against herpes simplex virus associated with the gel in the CAPRISA 004 study. The VOICE study also showed that among women who used the gel and had the product in their blood, there was a significant protective effect against herpes. We don’t know what those results will be for FACTS. If it’s also a strong signal there, we will have to take a step back and ask if there is a role for this gel in a defined population. The question will be who is that defined population?
The main message that we keep coming back to is that for the general population of women at highest risk for HIV, gels are not the way to go. We need to look at more user-friendly, sustained delivery systems, whether it’s injectable PrEP, vaginal rings or other devices, that women want to use.
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