Vaginal gel for HIV prevention so far ineffective in the real-world
Young women in Africa are in desperate need of an HIV prevention method that is acceptable to them – but science has so far failed to provide.
A vaginal gel designed to prevent HIV in women has been shown to be ineffective in a population of young women aged 18-30 in South Africa because of issues relating to adherence and consistency of use.
Preliminary results of the Follow on African Consortium for Tenofovir Studies (FACTS-001) trial were previously reported in 2015 at the Conference for Retroviruses and Opportunistic Infections (CROI), but the full study has only now been peer reviewed and published in this month’s Lancet.
The FACTS-001 trial, led by the Wits Reproductive Health and HIV Institute in South Africa, was a Phase III clinical trial of a vaginal gel comprised of the antiretroviral drug, tenofovir, used before and after sex. The main outcome of the study was to assess whether use of the gel could prevent HIV acquisition among young women in the region, who remain the group most affected by HIV globally.
Other secondary outcomes included rates of herpes (HSV-2), pregnancy, pregnancy outcomes, gel and condom use, and HIV incidence following stopping use of the gel. Among women who became HIV-positive, drug resistance, CD4 t-cell count and viral load monitoring were also secondary outcomes of interest.
2,059 HIV-negative women were randomly assigned to receive a 1% tenofovir gel (no. 1,032) and a placebo (no. 1,027). The women had intensive adherence counselling, and women identified as high-risk for HIV and gender-based violence were given specialised support. The women were tested monthly for HIV over the course of the 27-month study.
At the end of the trial, 61 women became infected with HIV in the tenofovir arm and 62 women in the placebo arm. The results are decidedly sobering – the microbicide made no difference in the HIV infection rates of women.
The researchers blame adherence to the vaginal gel as the main reason for failure of the trial to meet the intended outcomes. Despite adherence counselling, just 19% of the tenofovir group and 18% of placebo group used the gel more than 80% of the times they had sex; 41% and 43% respectively in 50-80% of sex acts; and 40% and 39% respectively in less than 50% of sex acts.
Drug levels were also tested in a sub-cohort of the women, and positively, levels of tenofovir was associated with less risk of acquiring HIV. But a number of behavioural confounding factors could also be attributed to this association.
Adherence levels were worse in younger women, and researchers suggest that this group, the majority of whom live with their parents and may be having sex away from home, may be challenged to take the second post-coital dose of tenofovir. “Pericoital topical products might be suitable for some women—eg, those who have infrequent sex or who do not wish to use systemic products—but consistent use with every sex act remains a key challenge,” state the authors.
Indeed the topic of non-oral pre-exposure prophylaxis (PrEP) has been a ‘hot topic’ this month with a number of studies from the HIV Research for Prevention Conference (HIVR4P 2018) in Madrid reporting data relating to vaginal rings, long-acting implants, vaginal films, vaginal or rectal implants and gels – as reported by Aidsmap. Even oral PrEP is battling adherence issues in demonstration project with women on the continent.
These interventions may all be efficacious in principle, but they are showing little impact on populations they are supposedly for. In an accompanying commentary to the FACT-001 study results, Elvin H. Geng et al. ask if implementation science could be useful for bringing these biomedical interventions to intended populations – should it have a role earlier in the translational research process, even in efficacy trials?
“Investments in HIV prevention research, to date, have been largely directed towards assessing efficacy. Perhaps it is time to bring implementation considerations into focus from the beginning of the scientific process.”
Promising innovations include combining contraception and HIV prevention into one product for women – which could speak to a women’s more pressing needs.
Nelly Mugo of the Kenyan HIV Research Institute (KEMRI) said in the pre-conference satellite on PrEP reported by Aidsmap, “Young women in Africa want to avoid HIV, but what they want to prevent is pregnancy. Pregnancy can have life-changing effects too, and has a higher incidence than HIV infection.”
These options are currently being explored, but there remain significant scientific challenges combining the two interventions into one.
So while trials like FACT-001 and others are disappointing – embracing a human-centred design could overcome the challenge of getting effective HIV prevention to women in Africa.