NIH Launches HIV Prevention Trial of Long-Acting Injectable Medication in Sexually Active Women

Study to Test Efficacy, Safety of Injectable Cabotegravir Compared with Daily Oral PrEP
November 30, 2017

The first large-scale clinical trial of a long-acting injectable medication for HIV prevention in sexually active women has begun. The study in southern and eastern Africa 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 for HIV infection. 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. The U.S. National Institutes of Health (NIH) is sponsoring the trial, and the NIH-funded HIV Prevention Trials Network (HPTN) is conducting the study, called HPTN 084. 

“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 S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. “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 percent of new HIV infections among adults in southern and eastern Africa in 2016, so 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, M.B.B.Ch., Ph.D., the HPTN 084 protocol chair. “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.” Dr. Delany-Moretlwe is associate professor and director of research at the Wits Reproductive Health and HIV Institute at the University of the Witwatersrand in Johannesburg.

NIAID is sponsoring the Phase 3 clinical trial and co-funding it in a unique partnership with ViiV Healthcare and the Bill & Melinda Gates Foundation. ViiV Healthcare and Gilead Sciences Inc. are providing the study medications. The new trial complements HPTN 083, an ongoing NIH study launched in 2016 of long-acting injectable cabotegravir for HIV prevention in men who have sex with men and transgender women who have sex with men.

“HPTN 084 also will examine how women experience long-acting injectable cabotegravir—whether they find it desirable and usable,” said Mina Hosseinipour, M.D., M.P.H., 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.” Dr. Hosseinipour is professor of medicine at the UNC School of Medicine in Chapel Hill, North Carolina, and scientific director of UNC Project-Malawi in Lilongwe. 

The trial will enroll approximately 3,200 sexually active women aged 18 to 45 years at 20 sites in 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 enrollment, 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.

HPTN 084 study participants will receive HIV prevention counseling, condoms and lubricant, as well as counseling to encourage and support adherence to the daily pill. Participants will be tested for sexually transmitted infections (STIs) throughout the trial and referred for appropriate treatment if an STI is diagnosed. Participants will be tested for HIV at least every eight weeks, and those who become HIV-infected during the trial will stop receiving the study products and be referred to local medical providers for appropriate HIV care and treatment. 

For more information about HPTN 084, please see Questions and Answers: The HPTN 084 HIV Prevention Study below, and visit ClinicalTrials.gov under study identifier NCT03164564.

Question & Answer: 

The HPTN 084 HIV Prevention Study

What is the HPTN 084 study?

HPTN 084 is the first large-scale clinical trial of a long-acting injectable drug for HIV prevention in women. The study will examine whether a long-acting form of the investigational anti-HIV drug cabotegravir, injected once every eight weeks, can safely protect women from HIV infection. The study also will investigate whether women find injectable cabotegravir appealing and easy to use. A similar study is taking place in men, as described in the answer to question 4 below.

Why is NIAID conducting HPTN 084?

Currently, the only drug regimen licensed for HIV pre-exposure prophylaxis, or PrEP, is the anti-HIV medication Truvada taken daily as an oral tablet. If long-acting injectable cabotegravir is found to be effective for HIV prevention in women, it would give women a choice of biomedical HIV prevention tools. Taking a daily pill can be challenging for some people, who may find that an every-eight-week injection schedule is more convenient. Thus, if periodic injectable cabotegravir is found to be effective for PrEP, it may be an easier option for some people to adhere to than a daily oral pill. In addition, some people may find periodic injections to be a more discreet form of HIV prevention than daily pills, and thus may prefer injectable cabotegravir for that reason. 

Who can participate in HPTN 084?

The study seeks to enroll approximately 3,200 women aged 18 to 45 years.

Is injectable cabotegravir being tested for HIV prevention in men also?

Yes, an ongoing study called HPTN 083 is testing the safety and efficacy of injectable cabotegravir for HIV prevention in men who have sex with men and transgender women who have sex with men. That study began in 2016 and is taking place in seven countries in the Americas, Asia and Africa.

Where will HPTN 084 take place?

The study will enroll participants at 20 sites in Botswana, Kenya, Malawi, South Africa, Swaziland, Uganda and Zimbabwe.

Why is HPTN 084 taking place only in sub-Saharan Africa?

The study is taking place only in sub-Saharan Africa because more women become infected with HIV there than in any other region of the world. In 2016, women accounted for 57 percent of new HIV infections among adults in sub-Saharan Africa. Women comprise 45 percent or less of newly HIV-infected adults in other regions.

When did HPTN 084 begin, and when are results anticipated?

HPTN 084 began in November 2017, and results are anticipated in 2022.

Who is sponsoring, funding and conducting HPTN 084?

The National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health, is sponsoring HPTN 084 and is co-funding the trial in a unique partnership with ViiV Healthcare and the Bill & Melinda Gates Foundation. The NIH-funded HIV Prevention Trials Network (HPTN) is conducting the study, while ViiV Healthcare and Gilead Sciences, Inc. are providing cabotegravir and Truvada, respectively.

What is the study design?

Half of the HPTN 084 study participants will be randomly assigned to the cabotegravir group and half to 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 their first five weeks after enrollment, all study participants 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. 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. This is to provide continued protection from HIV during the period when cabotegravir levels drop below the threshold expected to be protective. Participants will be tested for HIV at least once every eight weeks throughout the study. 

How is NIAID ensuring the safety of HPTN 084 study participants?

Multiple individuals and groups will carefully monitor the safety of HPTN 084 study participants. The principal investigators at study sites will quickly report and manage any adverse health outcomes, and staff at the HPTN’s Statistical and Data Management Center will monitor reports of safety data from the sites. In addition, a Clinical Management Committee will assist principal investigators if unexpected safety concerns arise. 

Furthermore, both a Study Monitoring Committee and an independent Data and Safety Monitoring Board (DSMB) will conduct periodic reviews of participants’ safety. A DSMB is composed of clinical research experts, statisticians, ethicists and community representatives who meet periodically during a study to review safety and efficacy data as it is gathered. A statistician who is not part of the study team presents interim data to the DSMB. The DSMB alerts the study team if anything appears to compromise the safety of study participants, if there is compelling evidence that the study intervention is effective, or if it becomes clear that the study cannot answer one of the questions it was designed to address. If indicated, the DSMB may advise that the study be ended early.
 

What HIV preventive care will study participants receive?

HPTN 084 study participants will receive HIV prevention counseling, condoms and lubricant, as well as counseling to encourage and support adherence to the daily oral pill. Participants will be tested for HIV at least once every eight weeks. Participants also will be tested for sexually transmitted infections (STIs) throughout the study and referred for appropriate treatment if an STI is diagnosed. 

What will happen to study participants who acquire HIV infection during the trial?

Study participants who acquire HIV infection during the trial will stop receiving the study products and will be referred to local medical providers for appropriate HIV care and treatment in accordance with national guidelines and standards.

Content last reviewed on November 30, 2017