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An extension of a long-acting cabotegravir study shows safety prior to and during pregnancy in cisgender women, with full results being presented at the 2024 International AIDS Conference.
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Trial Name: Evaluating the Safety and Efficacy of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women
ClinicalTrials.gov ID: NCT03164564
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Completion Date (Estimated): November 30, 2024
According to new research, a long-acting injectable of cabotegravir (CAB-LA, Apretude; ViiV Healthcare) is safe and well-tolerated before and during pregnancy when used as HIV pre-exposure prophylaxis (PrEP). The follow-up phase trial (NCT03164564) included cisgender women, with more than 300 pregnancies and infants.1
CAB-LA, which is administered intramuscularly every 2 months, was previously shown to be an effective HIV prevention method; however, data on the safety of the injection during pregnancy was limited. The open-label extension study of the CAB-LA efficacy trial included women who did not have HIV and had the potential to become pregnant during the study. Participants were monitored for both pregnancy-related adverse events (AEs)—such as gestational hypertension, pre-eclampsia, and weight gain—and infant outcomes—such as miscarriage, stillborn or intrauterine fetal death, premature birth, or low birthweight.1,2
A total of 367 pregnant women were enrolled in the trial. All women received a 3-step regimen with different treatments or placebos depending on the group they were placed in. Arm A received the following: daily oral CAB (30 mg) with oral tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) placebo for 5 weeks (step 1), injections of CAB-LA at 2 time points 4 weeks apart and every 8 weeks after that time followed by daily oral TDF/FTC placebo at week 5 (step 2); and daily TDF/FTC for up to 48 weeks no later than 8 weeks following the last injection (step 3). Additionally, arm B received the following: daily oral TDF/FTC (300 mg/200 mg) and placebo (in place of oral CAB) for 5 weeks (step 1); daily TDF/FTC and placebo (in place of CAB-LA) at 2 time points 4 weeks apart, and every 8 weeks after that time beginning at week 5 (step 2); and daily TDF/FTC for up to 48 weeks no later than 8 weeks following the last injection (step 3).2
The findings indicated that pregnancy-related maternal AE incidence was 45.7, 47.1, and 37.5 per 100 person years among those who used CAB-LA during pregnancy, prior to pregnancy, or without CAB-LA use, respectively. Additionally, infant outcomes were shown to be similar across groups, with negative outcomes reported in 33%, 38%, and 27%, respectively, of pregnancies in these respective groups. The investigators note that there was 1 major congenital anomaly reported in a participant who received CAB-LA, with no maternal deaths occurring throughout the study population.1
CAB-LA was considered to be safe and well-tolerated in this patient population, both prior to and during pregnancy. The analysis’s outcomes were presented at the 2024 International AIDS Conference in Munich, Germany, which was held July 22 to July 26.1
“Cisgender women experience biological changes and social dynamics that can increase their likelihood of acquiring HIV during pregnancy and the postnatal period, and we need to offer them evidence-based options when they may need them most,” said Jeanne Marrazzo, MD, MPH, director of the National Institutes of Health's (NIH) National Institute of Allergy and Infectious Diseases (NIAID), in a news release. “These data provide reassurance about long-acting injectable cabotegravir for HIV prevention during pregnancy.”1
In 2020, the first large-scale clinical trial to show high efficacy of the long-acting injectable form of HIV prevention in cisgender women was conducted. The findings demonstrated that among the 38 women who acquired HIV, 4 received CAB-LA and 34 oral CAB. According to the investigators, this translates to an HIV incidence rate of 0.21% (95% CI 0.06%-0.54%) in the CAB-LA group and 1.79% (95% CI 1.24%-2.51%) in the oral CAB group. Additionally, the investigators noted that although both PrEP methods were effective in the prevention of HIV acquisition, CAB-LA’s protective effects met the statistical criteria for superiority (HR, 0.11; 95% CI 0.04-0.32). Both treatments were well-tolerated among the enrolled women and demonstrated no safety concerns, with the most common AE being pain or tenderness at the injection site.3
“The overlap between high HIV incidence and the specific risks that cisgender pregnant women face in acquiring HIV in many countries calls for diverse and highly effective PrEP options as part of sexual and reproductive health approaches,” said study chair Sinead Delany-Moretlwe, MBBCh, PhD, director of research at Wits RHI, professor of global health and infectious diseases at the University of the Witwatersrand, Johannesburg, in the news release. “We hope that these findings can fill an important knowledge gap that can help increase access to this highly effective HIV PrEP option among cisgender women before, during, and after pregnancy.”1
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