The results of the trial were considered so impressive that it was halted early on the basis of the preliminary results, which were released November 9. The study was originally designed to continue through 2022. “I don’t think we can overemphasize the importance of this study,” said Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID), in a briefing on November 9. “One of the stumbling blocks in our prevention modalities is the inconsistency or lack of efficacy of preexposure prophylaxis in those who need it the most, namely young women,” Dr. Fauci said. Worldwide, there are about 17.4 million adult women living with HIV, approximately 51 percent of the global total, according to the World Health Organization (WHO). In East and Southern Africa, HIV prevalence among young women between the ages of 15 and 24 is 1.6 million, more than double that of young men. In the United States, there were 1.1 million people with HIV at the end of 2016, 258,00 of them women, according to the Centers for Disease Control and Prevention (CDC).
Better Adherence Leads to Greater Efficacy
The trial, known as HIV Prevention Trials Network 084 (HPTN 084), began in November of 2017 with 3,223 women. Participants were ages 18 to 45 years old, at risk for acquiring HIV infection, and lived in one of seven countries in sub-Saharan Africa. One group of women received cabotegravir through a shot every eight weeks, while the other group were assigned to take a daily dose of oral Truvada. Before the trial was stopped, a total of 38 women acquired HIV, four from the cabotegravir arm of the study and 34 from the Truvada arm. Although both methods were effective in preventing the infection, the cabotegravir injection was 9 time more effective than the once daily pill. “These types of prevention trials are called endpoint driven trials, which means that they’re designed to compare the number of new infections acquired by the women in each group,” explains Alex Rinehart, PhD, senior director with Global HIV Prevention Strategy at ViiV Healthcare, the maker of the injectable drug. Greater adherence in the cabotegravir injection group appears to be the main driver for cabotegravir’s superior efficacy in preventing HIV, says Dr. Rinehart. “The rate of the return for each of the injection visits in the women study was greater than 90 percent,” he says. “These results follow similar results from a companion trial, HTPB 083, that was conducted in men who have sex with men and transgender women who have sex with men,” says Rinehart. “That trial was also stopped in May of this year for a superiority finding in favor of cabotegravir over the same drug, the daily oral pill, Truvada,” he says. RELATED: How to Talk to Your Doctor About Preventing HIV
‘Real World’ Adherence With Cabotegravir an Unknown
Adherence to the cabotegravir injection was very good in the trial, but that’s a highly controlled environment compared with the real world, says Jenell Coleman Fennell, MD, MPH, director, division of gynecologic specialties and associate professor of gynecology and obstetrics at Johns Hopkins Medicine in Baltimore, Maryland. Dr. Fennell was not involved in the trial. “Clinical trials have a lot of staff to help people comply with the protocol, which is different than the real world when you don’t have all that other support,” says Dr. Fennell. “You definitely need someone who’s really motivated to come in every two months to a clinical site to get an injection on time,” she says. “I can say that in my experience as an ob-gyn, we give out the contraceptive method Depo-Provera, which is a shot every three months. We actually have quite a number of women who may show up late for their depo shot,” she says. Part of translating the success in the trial to outside world could depend on how much “wiggle room” there is — that is, can the drug still be effective in preventing HIV if women are late getting the injection, says Fennell. “It will be interesting to see how much leeway women will have in terms of getting that next injection, because the drug levels start to wane and they’re at risk of acquiring HIV,” says Fennell. Experts have noted that cabotegravir can still be detected in the body for much longer than two months, according to a presentation at the Virtual 2020 National Ryan White Conference on HIV Care and Treatment summarized at HIV.gov. That could mean that the injections could be spaced out even further. RELATED: HIV Positive Women With Depression Have Higher Risk of Heart Disease
Education And Awareness Needed to Protect More Women From HIV Infection
Part of the problem of protecting women from HIV infection in the United States is that a lot of women who are at risk may not be aware that they are, says Fennell. “So even though it’s exciting that we have this new medication out that will soon be on the market, we still have to do a lot more work to do,” she says. There needs to be resources devoted to raising awareness in the women who are at risk for acquiring HIV, says Fennell. “Then they can self-identify as being at risk and make the decision about using whichever form of protection we have out there, whether it’s a pill or an injection,” she says. “Hopefully, the makers of cabotegravir will be able to include women in the marketing and education around the drug in a way that hasn’t been done before in HIV prevention,” says Fennell. RELATED: 10 Facts About HIV/AIDS Everyone Should Know
Will Cabotegravir Be Affordable?
In theory, the injection could help protect the most vulnerable patients from HIV and improve disparities in care, says Fennell. Whether that actually happens will be largely determined by whether cabotegravir will be covered by insurance, however. “If this rolls out and insurance companies, especially Medicaid, don’t cover it or the copay is extremely high, that may further exacerbate the health inequities that we have,” says Fennell. The makers of cabotegravir say that it’s too early to know what the cost of the drug will be for consumers, but they are committed to making the drug accessible to lower- and middle-income countries. “It’s part of our corporate policy, and that’s something that we’re working on right now,” says Rinehart. Cabotegravir is currently approved and available in Canada from Johnson & Johnson for treatment of HIV as part of a combination drug marketed as Cabenuva. The company plans to submit the necessary regulatory package to the U.S. Food and Drug Administration (FDA) in the first half of next year in 2021, and then other regulatory agencies will follow after FDA, says Rinehart.
