Global trial of long-acting injectable PrEP for gay men and trans women stopped early following success
Long-acting, injectable cabotegravir is as effective as daily PrEP pills at preventing HIV among cisgender men and transgender women who have sex with men.
When provided every two months as an injectable pre-exposure prophylaxis (PrEP), investigational drug cabotegravir prevents 69% more HIV infections compared to the current standard of care for PrEP among HIV-negative cisgender men and transgender women who have sex with men.
The data comes from an interim analysis of the HIV Prevention Trials Network (HPTN) 083 study which is investigating the effectiveness of long-acting cabotegravir (CAB LA) injected once every eight weeks. It is the first large-scale clinical trial of a long-acting injectable drug for HIV prevention, with almost 4,600 HIV-negative people from more than 40 sites in North and South America, Asia and Africa enrolled.
The analysis revealed that CAB LA was non-inferior to daily oral PrEP, which consists of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). A final analysis is needed to determine if CAB LA is superior. As the study objective was met with one year left, the independent ethics board halted the trial and all participants were offered CAB LA should they want it.
What did the study do?
In this randomised, double-blind control trial, cis men and trans women at-risk of HIV were randomly assigned to receive either injectable CAB LA or oral FTC/TDF drugs.
From November 2016, when study enrolment started, a total of 50 people became infected with HIV. Twelve infections were among people randomised to receive CAB LA, while 38 infections were among people taking oral FTC/TDF, translating to an HIV incidence rate of 0.38% and 1.21% respectively.
While the results strongly suggest superiority of CAB LA over oral FTC/TDF, full results and analysis need to be published and subjected to peer review. Further analysis is also needed to understand why infections occurred despite taking PrEP.
Safety was similar between the two groups and side-effects were mild. Discontinuation due to injection site reactions or injection intolerance in the CAB LA arm of the study was 2%, compared to no discontinuations due to injecting reactions using the placebo in the FTC/TDF arm.
Participants lived in Argentina, Brazil, Peru, United States, South Africa, Thailand and Vietnam. Two-thirds of study participants were under 30 years of age, and 12% were transgender women. Half of the participants in the United States identified as black or African American.
Kimberly Smith, M.D., Head of Research & Development at ViiV Healthcare, the drug’s developer, said, “We are thrilled with the results not only because of the high efficacy of cabotegravir but also because we have demonstrated high efficacy in a study that adequately represents some of the populations most disproportionately impacted by HIV -- black MSM in the US, young MSM globally and transgender women.”
What does long-acting mean and why is it important?
A long-acting drug – in the form of a pill, injectable or an implant – is a type of treatment that does not need to be taken every day. This is important because HIV drugs require very high levels of adherence in order for them to be effective, yet many people find daily pill-taking difficult.
Long-acting formulations, such as cabotegravir, are set to revolutionise treatment options by spacing the number of times one has to take their drugs. They aren't a magic bullet for solving all problems relating to treatment-taking, but they provide another option for people. Cabotegravir formulations are currently being investigated in a number of trials for the treatment of HIV infection and as PrEP.
While CAB LA taken as PrEP can prevent HIV without relying on adherence to a daily pill, many people also prefer long-acting options because they are more discreet.
In a press release, UNAIDS said the findings will have ‘significant impact’. Subject to regulatory approval and accessible drug pricing, men who have sex with men will be able to choose between three ways to use PrEP: daily pills, pills taken before and after sexual activity (event-driven PrEP) or an injection every two months. Transgender women will be able to choose between injections or daily pills. Event-driven PrEP is not yet recommended for transgender women due to possible drug interactions with some hormones.
What about non-trans women?
Women make up the majority of new HIV infections worldwide and are a key affected population for HIV, particularly in sub-Saharan Africa. However there exist few women-led HIV prevention tools.
Trials assessing the safety and efficacy of CAB LA as PrEP for non-trans women are currently underway in HPTN 083’s sister trial, HPTN 084, which started enrolment a year after HPTN 083. To date, more than 3,000 sexually active women in seven African countries have enrolled in the study and interim results are expected in November.
Women in Africa face unique challenges around adherence to PrEP, particularly where they may not have agency over their own health and where there is stigma around HIV. Studies have found that this population would prefer injectable PrEP over daily oral PrEP. PrEP may be even more acceptable when combined with an injectable contraceptive, which trials will need to assess.
“We are eagerly awaiting the results of the ongoing HPTN 084 study among African women,” said Dr Hader of UNAIDS. “We hope that by the end of this year there will be equally good news for women around the world.”