Long-acting PrEP for women – ‘hugely significant’ for the HIV response
News the HIV world has been waiting for – long-acting injectable cabotegravir (CAB LA) is a potentially game-changing tool to prevent HIV in women.
In an interim analysis of a large-scale clinical trial, long-acting, injectable pre-exposure prophylaxis (PrEP) offered once every two months was more effective than daily oral PrEP at preventing HIV in a population of cisgender women in Africa.
The results usher in a new era of HIV prevention options for women, who have so far had to rely on condom use, daily pill-taking or abstinence. These methods bring specific challenges for women – who lack control over their reproductive and general health due to unequal gender roles.
According to an independent interim analysis of ‘HPTN 084’ – a double-blind randomised control trial – the novel drug CAB LA was 89% more effective than daily oral tenofovir/emtricitabine (Truvada), the only other drug approved for PrEP.
The findings do not mean that daily PrEP was ineffective. It is already known that, when used consistently and correctly, daily oral tenofovir/emtricitabine can virtually eliminate the chance of HIV infection. But injectable PrEP offers people who may struggle with daily adherence the ability to experience the full benefits of PrEP - without the pill burden.
As a result of the overwhelming superiority of CAB LA for this population of women, the independent trial review board stopped the trial’s blinded arm and ordered all women be offered CAB LA should they want it.
If this all sounds familiar, it’s because back in May, Avert reported on the findings of the companion trial to HPTN 084 – HPTN 083 – which found the same drug to be safe and highly effective at preventing HIV among cisgender men and transgender women who have sex with men. In this study, interim results reported a 69% increase in effectiveness when compared to daily pills.
This present study enrolled 3,223 women aged 18 to 45 at an increased risk of HIV across seven countries in East and Southern Africa (Botswana, Kenya, Malawi, South Africa, Eswatini, Uganda and Zimbabwe).
Four HIV infections occurred among women randomly assigned to the cabotegravir injectable arm of the study, compared to 34 infections in the arm that was randomly assigned to daily oral PrEP. The risk of HIV was nine-fold lower with cabotegravir injections than with daily oral PrEP. The study authors have not yet analysed why infections in the CAB LA arm occurred.
The results have been described as ‘hugely significant’ by UNAIDS Executive Director Winnie Byanyima. “UNAIDS has long been calling for additional, acceptable and effective HIV prevention options for women, and this could be a real game-changer,” she said.
“If donors and countries invest in rolling out access of injectable PrEP to women at higher risk of HIV, new infections could be dramatically reduced.”
While the findings are a welcome positive development for 2020 – there remain a few unanswered questions that are specific to women.
- Injectable PrEP does not overcome all adherence challenges. CAB LA needs to be administered in a health facility, meaning people still have to come into the clinic every two months to receive their injections. This could present a barrier to implementation for both the health facility and patient, by further medicalising PrEP. Check out Avert’s reporting on the challenges of adherence for injectable PrEP in June.
- CAB LA has a ‘long tail’ – meaning that a detectable level of the drug persists in the body for a long period after someone stops taking it. During this period, the level of cabotegravir in the blood may not prevent HIV, but it could be enough for a person to develop viral resistance should they become infected with HIV. What’s more, for women, the median time to undetectable cabotegravir is 66 weeks, compared to 43 weeks in men. During this time, optimal adherence to other HIV prevention methods, including daily oral PrEP and condoms, is required.
- Additional information on the benefits for adolescent girls. Adolescent girls in Africa are disproportionately burdened by HIV and face similar barriers to young women. Data from South Africa in particular shows that girls aged 15-19 are four times more likely to get HIV than their male counterparts. The LIFT Study (HPTN 084-01) is currently examining whether CAB LA is safe and acceptable for adolescent females and have enrolled 50 adolescents from South Africa, Uganda, and Zimbabwe.
- Safety during pregnancy and breastfeeding. Very few women became pregnant during HPTN 084 because of the requirement that they also receive long-acting contraception. Further trials will need to monitor if CAB LA has any adverse effects on foetal and pregnancy outcomes.
In a press release, the World Health Organization (WHO) note that CAB LA has the potential to increase choice and overcome some of the barriers related to adherence for long-term use of biomedical HIV prevention. But open-label extension trials are needed to improve our understanding of some of the safety concerns listed above, and also the best implementation approaches to reach the women who could benefit from injectable PrEP.
Additionally, further research innovation is needed to find other ways to provide PrEP that may be more acceptable to women - like a PrEP implant, or a dual-method PrEP contraceptive.