Injectable PrEP could be ‘discreet’ HIV prevention option for women
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Injectable cabotegravir administered every 8 weeks was associated with approximately nine times fewer HIV infections among cisgender women than daily oral PrEP, according to the results of a phase 3 trial.
Sinead Delany-Moretlwe, MBBCh, PhD, DTM&H, a researcher at the University of the Witwatersrand in Johannesburg, presented findings from the HIV Prevention Trials Network 084 study (HPTN 084) during the HIV Research for Prevention virtual conference.
The trial compared ViiV’s long-acting injectable cabotegravir with oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) among cisgender women. Data from the trial were previously publicized by ViiV Healthcare in November, followed shortly by the FDA designating the drug a breakthrough therapy.
HPTN 084 was a companion trial to HPTN 083, which showed that the therapy was also effective among transgender women and cisgender men who have sex with men. Delany-Moretlwe said a licensure package for the therapy could be submitted to the FDA in 2021, with a decision possible by the end of the year.
“We need a range of HIV prevention options for women that can fit into their lives.
Currently many women have challenges with using either condoms — not under their direct control — or oral PrEP because of difficulty with daily pill taking, as well as concerns about the stigma, or fear of violence from partners, or judgment from family and community members, which may limit oral PrEP use,” Delany-Moretlwe told Healio.
“An injectable PrEP could be discreet and overcome some of these challenges,” she said. “We need to learn whether injectable cabotegravir was safe and effective in preventing HIV in cisgender women.”
More than 3K participants
To assess its effectiveness, Delany-Moretlwe and colleagues randomly assigned HIV-uninfected and PrEP-eligible cisgender women in a 1:1 ratio to received either active long-acting cabotegravir (CAB-LA) plus FTC/TDF placebo, or active FTC/TDF plus CAB-LA placebo. According to the study, participants received 5 weeks of daily oral product, followed by intramuscular injections every 8 weeks after an initial 4-week interval load alongside daily oral pills.
Overall, 3,224 participants were enrolled at sites in South Africa, Zimbabwe, Uganda, Malawi, Botswana, Eswatini and Kenya. Of these participants, 54% had two or more partners in the past month, 32% had a partner with HIV or unknown status, 19% had chlamydia and 7% had gonorrhea at enrollment, the researchers reported.
According to the study, a total of 38 incident infections occurred over 3,808 person-years (HIV incidence 1%; 95% CI, 0.71-1.37) four in the CAB-LA arm (HIV incidence 0.21; 95% CI, 0.06-0.54) and 34 in the TDF/FTC arm (HIV incidence 1.79%; 95% CI, 1.24-2.51) (HR = 0.11; 95% CI, 0.04-0.32). In a random subset of 375 TDF/FTC participants, 62% of plasma samples had detectable TDF/FTC and 46% had concentrations consistent with daily dosing, Delany-Moretlwe and colleagues said.
They noted that adverse events were mild to moderate and similar between trial arms, although injection site reactions were more common in the CAB-LA arm (32% vs. 9%) and nausea was more common in the TDF/FTC arm (9% vs. 5%).
According to Delany-Moretlwe, there are additional studies underway assessing CAB-LA in pediatric populations. Given the concerns that arose surrounding dolutegravir and neural tube defects among pregnant women taking the drug for HIV treatment, researchers required all women in HPTN 084 use a long-acting form of contraception out of an abundance of caution, given that dolutegravir is also an integrase inhibitor and similar to CAB, Delany-Moretlwe said. However, she said that, following the emergence of reassuring data on the use of dolutegravir in pregnancy, researchers have planned open-label extension studies on CAB-LA for use during pregnancy.
“CAB-LA is safe and effective in preventing HIV infection in cisgender women,” Delany said. “Women who received CAB-LA had an 89% lower risk of HIV infection compared to those who received daily oral Truvada, likely because 8-weekly injections overcame the adherence barriers associated with daily pill taking.”
‘You get more coverage’
When taken as prescribed, oral PrEP is difficult to beat as an HIV prevention method, Raphael J. Landovitz, MD, professor of medicine at the University of California, Los Angeles Center for Clinical AIDS Research and Education, told journalists in a preconference webinar. But the medication is not always taken as prescribed, said Landovitz, who —like Delany-Moretlwe — hypothesized that this explains why CAB-LA has outperformed daily oral PrEP in trials.
“It’s easier to not have to remember to take a pill, so you get more coverage,” Landovitz said. “People who have other priorities find it difficult to take a pill enough to keep high levels of drug” in their system.
Monica Gandhi, MD, MPH, professor of medicine at the University of California, San Francisco, previously told Healio that scientists will need to confirm that the “breakthroughs” coming out of the injectable CAB-as-PrEP studies “did not occur with integrase inhibitor resistance, as that would curtail the ability to use first-line dolutegravir-based therapy for their treatment.” Landovitz said the COVID-19 pandemic has slowed down the analysis of samples and that resistance data are expected in first quarter of 2021.
Scientists told reporters during the conference that it is too early to tell how much CAB-LA will cost, but that both HPTN trials are doing cost-effectiveness analysis, which will help inform what the price will be.
The FDA recently approved a long-acting injectable regimen containing CAB for HIV treatment. The therapy consists of monthly injections of CAB and rilpivirine, with a cost close to the top range of daily oral therapies on the market, ViiV said.
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Delany S, et al. Abstract 1479. Presented at: HIV Research for Prevention; Jan. 27-28 and Feb. 3-4, 2021 (virtual meeting).
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