Uganda and Kenya are among seven African countries carrying out large-scale clinical trials of a long-lasting injectable pre-exposure prophylaxis (PrEP) in sexually active women.
The trials, called HPTN 084 and sponsored by the US National Institutes of Health, will also be conducted in Botswana, Malawi, Swaziland, South Africa and Zimbabwe and will examine whether a long-acting form of the investigational anti-HIV drug cabotegravir injected once every eight weeks can safely protect women at risk of HIV infection.
Injectable cabotegravir (CAB) is considered better than a combination of daily oral HIV drugs — Tenofovir disoproxil fumarate 300mg plus Emtricitabine 200 mg (TDF/FTC).
The only drug regimen currently licensed for HIV pre-exposure prophylaxis, or PrEP, is the anti-HIV medication Truvada taken daily as an oral tablet.
Kenya and South Africa are the only countries in Africa where oral PrEP has been rolled out as one of the prevention interventions for high risk HIV-negative people.
HPTN 084 will enroll HIV-uninfected, sexually active women. The participants will be assigned by chance to either CAB or TDF/FTC in a double-blind manner, meaning neither the participant nor research staff know what the participant is receiving.
Study participants will be transitioned to locally available HIV prevention services when their participation in the study, conducted by NIH-funded HIV Prevention Trials Network , ends.
“This new study, driven by African women scientists and volunteers, is testing the efficacy of a new HIV prevention tool for women who need more options for protection,” said Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.
“Taking a daily pill can be challenging for some people. For some women, a long-acting injectable form of protection may be an easier, more desirable and discreet alternative.”
Women accounted for 58 per cent of new HIV infections among adults in Southern and East Africa in 2016, thus protecting them from acquiring the virus is essential to controlling the HIV epidemic.
Current data suggest that women who use oral Truvada for HIV prevention may need to take it every day, without fail, to achieve and maintain drug concentrations high enough to provide protection. Truvada consists of two anti-HIV drugs, emtricitabine and tenofovir disoproxil fumarate.
“Injectable cabotegravir has the potential to give sexually active women a choice of biomedical HIV prevention tools for the first time--somewhat similar to the choices available to women for contraception,” said Sinead Delany-Moretlwe, the HPTN 084 protocol chair and associate professor and director of research at the Wits Reproductive Health and HIV Institute at the University of the Witwatersrand in Johannesburg.
“Current HIV prevention tools can be especially difficult for women to control or negotiate with a partner. An effective, long-acting injectable drug would allow a woman to discreetly protect herself from HIV during sex.”
“HPTN 084 will also examine how women experience long-acting injectable cabotegravir —whether they find it desirable and usable,” said Mina Hosseinipour, the HPTN 084 protocol co-chair.
“Understanding what types of HIV prevention fit best in women’s lives will help further refine HIV prevention research, delivering tools that are ultimately safe, effective and desired.”
The trial will enroll approximately 3,200 sexually active women aged 18 to 45 years at 20 sites in the seven countries in southern and eastern Africa.
The women are randomly assigned to either the cabotegravir group or the Truvada group. Neither the participants nor the study team will know who is in which group until the end of the trial.
Participants will be in the study for an average of 3.6 years. During the first five weeks after enrolment, they will receive two daily oral tablets: Either cabotegravir or Truvada, and a placebo pill.
Beginning in the sixth week, participants in the cabotegravir group will receive injections of cabotegravir and placebo tablets to be taken orally daily, while participants in the Truvada group will receive placebo injections and Truvada tablets to be taken orally daily.
Injections will be administered by study staff. The first two injections will be four weeks apart, then once every eight weeks for an average of 2.6 years.
After completing the injections, all participants will be offered 48 weeks of PrEP with daily oral Truvada.
Subsequently, all participants will be transitioned to locally available HIV prevention services for PrEP, as available. Study results are expected in 2022.
A related study, HPTN 083, is testing the safety and efficacy of injectable CAB for HIV prevention in 4,500 men who have sex with men and transgender women who have sex with men in seven countries in the Americas, Asia and Africa.
“If cabotegravir is shown to protect against HIV acquisition, the long-acting injectable agent could become another major tool in our HIV prevention toolbox,” said Myron Cohen, HPTN co-principal investigator and director of the Institute for Global Health and Infectious Diseases at the University of North Carolina at Chapel Hill.