Finally, hope for a better HIV prevention option for women. Here’s what we know about cabotegravir and what we don’t.
Resource Details: Press briefing hosted by the University of the Witwatersrand’s Reproductive Health and HIV Institute, HIV Prevention Trials Network Press (HPTN) press briefing, HPTN fact sheet.
*These results have not yet been published.
Announcement Date: 9 November 2020
What was the study about?
This phase three, double-blinded trial, called HPTN 084, is the first study to test whether a long-acting injection of cabotegravir given once every two months works better to prevent HIV in cisgender women than taking the HIV prevention pill Truvada daily. Truvada consists of the two anti-HIV drugs emtricitabine and tenofovir disoproxil fumarate.
Watch the researchers talk about the study
*Note on Publication of study:
The results of the HPTN 084 trial, also called the LIFE (Long-Acting Injection for the Epidemic) study was released ahead of publication. The early results of the research were so promising that the independent expert group that reviewed the study, the Data and Safety Monitoring Board (DSMB), recommended that the blinded phase of the trial be stopped early. In other words, participants who were initially given a dummy injection of cabotegravir will now instead be given the actual drug for the rest of the duration of the study. The recent results will be published in the coming months, according to Sinead Delany-Moretlwe, who headed up the study.
How was the study conducted?
- The LIFE study took place at 20 sites in seven countries in Sub-Saharan Africa, including Botswana, Eswatini, Kenya, Malawi, South Africa, Uganda and Zimbabwe between 2017 and 2020. Watch the HPTN briefing.
- 3 224 HIV negative women participated.
- Participants were between the ages of 18-45 and at a high risk of becoming infected with HIV.
- A total of 3 127 participants were included in the analysis conducted by the data safety and monitoring board review.
- The mean age of study participants was 26 years and 57% of participants were 25 years or younger.
- 82% of the participants were not living with their sexual partner, 55% reported two or more sexual partners in the past month, and one third had a primary partner who was living with HIV or had an unknown HIV status.
- Participants were randomly assigned to one of two groups, A or B. The trial was also split into three steps. Watch the explanation from the researchers.
- In step one, group A was given a daily cabotegravir pill as well as a Truvada placebo for five weeks.
- Group B was given a dummy daily pill of cabotegravir and daily oral Truvada for five weeks.
- For step two, both groups’ cabotegravir pills were changed to eight-weekly cabotegravir injections. The first two injections are given four weeks apart and eight weeks apart from then on. Group B’s injection was a placebo. The groups were then monitored for up to 3.5 years.
- In step 3, cabotegravir was phased out and both groups were given active Truvada and a full HIV prevention package of services such as counselling and transitioned to local HIV services.
Key findings of the study:
- The study found that long-acting cabotegravir injected once every eight weeks was superior to the daily oral Truvada for preventing HIV in cisgender women. Long acting cabotegravir is 89% more effective than Truvada, the research reveals. Thirty eight women in the trial contracted HIV. Four were taking cabotegravir and 34 were receiving daily oral Truvada. This means there is nine times the number of HIV infections in those taking Truvada compared to the cabotegravir arm.
- The manufacturer, ViiV Healthcare, has not yet set the cost of cabotegravir.
- This is the first time such a significant HIV prevention result for women has been seen.
- An earlier study, HTPN 083, found long-acting cabotegravir was also more effective than Truvada at preventing HIV among cisgender men and transgender women.
What scientists still need to find out:
- Is cabotegravir safe for adolescent girls?
A bridging study to assess the safety of long acting cabotegravir in adolescent girls has begun. 50 girls younger than 18 will participate in this research.
- What about pregnant and breastfeeding women?
The open label extension study will be needed to monitor risks that the eight-weekly HIV prevention jab could pose to pregnant women and their unborn babies. Very few women became pregnant during the HPTN 084 trial due to a protocol amendment which required that all participants take long acting contraceptives.
- Real-world implementation issues
Where and how the cabotegravir shot will be delivered, and whether people will accept the change in treatment must still be considered, according to the World Health Organisation.
- Risk for drug resistance?
Injectable cabotegravir can stay in the body for months after a shot. These small amounts of the drug in the system may not be enough to protect against HIV infection and could result in the development of drug resistant HIV following exposure during this time. So far, researchers don’t know if there is any significant risk of drug resistance.
- At this stage, it is recommended that LIFE trial participants who stop taking long acting cabotegravir, either by choice or at the end of the trial, are offered Truvada to fill this possible gap. This might not be necessary but must still be confirmed in future research.
The LIFE study has been unblinded – so what happens next?
- The participants will be told which drug they were taking.
- Once all the regulatory reviews are complete, participants will be given the chance to continue to participate in the open label study (in other words, a study in which both the participants and researchers know who gets which medication).
- This study will run for at least 48 weeks up to two years. Ways to integrate HIV prevention into family planning services will be looked at.
- Helen Rees, the executive director of the Wits Reproductive Health and HIV Institute (WHRI) at the University of the Witwatersrand, says there are additional scientific and clinical questions that still require answers.
- “We’re not looking at something that’s going to be available immediately. But clearly, this is going to be fast tracked both from the clinical research point of view and the manufacturing side. Access to this for a country like ours with such high numbers of infected young women and new infections every year – it could be a game changer.”
- WHRI’s Sinead Delany-Moretlwe says the results reflect the desire that women have for a range of prevention options that will easily fit into their daily lives.
- She is the protocol chair of the trial and is also affiliated to the HIV Prevention Trials Network.
- Delany-Moretlwe says taking injections every eight weeks also allows for more privacy. “Taking an injection, eight weekly, is far easier for many women than taking a pill a day. But also, the social pressures that come with having bottles of pills around and people assuming that they’re sexually active, assuming that they may be HIV positive. injections are discreet, they fit into women’s lives,” she says.
Cabotegravir is a huge win for women: Here’s what the experts and activists say
- “This is extremely encouraging and exciting news for women around the world,” says Maureen Luba Milambe, the regional advocacy advisor for the Aids Vaccine Advocacy Coalition’s (Avac) Africa arm.
- Policy makers, funders and communities must now urgently design and build HIV prevention programmes and health systems that can deliver the growing array of biomedical PrEP options, says Mitchell Warren, the executive director at the Aids Vaccine Advocacy Coalition. “Key to those efforts will be ensuring that we don’t repeat the delays that have slowed daily oral PrEP rollout over the past eight years,” he says.
- Yvette Raphael, executive director of Advocacy for Prevention of HIV and Aids (APHA), says COVID-19 has shone a light on the epidemics of sexual and gender-based violence that help drive HIV. “To be truly effective, injectable HIV prevention and other biomedical options must also be accompanied by investments in women-led work to break the cycles of violence in our societies.”
- These results are hugely significant in the fight to eradicate HIV, says Winnie Byanyima, the executive director at the Joint United Nations Programme on HIV/AIDS (UNAids). “This could be a real game changer. 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.”
- The World Health Organisation says long acting cabotegravir gives women who are at a high risk of contracting HIV a better choice – especially for those who struggle to take a daily tablet or who don’t want to.