Is long-acting cabotegravir safe as PrEP for expecting mothers?

The use of long-acting injectable cabotegravir (CAB-LA) as a pre-exposure prophylaxis (PrEP) during pregnancy appears to be safe and well tolerated in cisgender women, according to the initial data of HPTN* 084 open-label extension (OLE) study presented at AIDS 2024.

CAB-LA is FDA-approved for people with vaginal exposure to HIV; however, for people with PrEP indications in pregnancy, CAB-LA dosing, efficacy, and safety remain unknown. If a person receiving CAB PrEP becomes pregnant, the limited available safety data and long half-life of CAB should be discussed with the patient with shared decision-making around ongoing PrEP use and options. [https://clinicalinfo.hiv.gov/en/guidelines/perinatal/pre-exposure-prophylaxis-prep-prevent-hiv]

Until additional data are accumulated regarding the safety of CAB-LA in pregnancy, providers may want to proceed with caution when using CAB-LA in women of reproductive potential. [Open Forum Infect Dis 2022;9:ofac230]

In the HPTN 084 OLE study, the researchers included 2,472 participants who were offered the choice between open-label CAB-LA and oral tenofovir diphosphate plus emtricitabine (TDF/FTC) for PrEP. Participants were divided into three groups according to CAB-LA exposure, such as during pregnancy (active CAB-LA group), prior to pregnancy only (prior CAB-LA group), or no CAB-LA use (TDF/FTC group). Confirmed pregnancies were defined as two positive tests on two separate urine samples on the same day. [AIDS 2024, SY2503]

There were 367 confirmed pregnancies observed, with an overall incidence rate of 12 per 100 person-years. “This was fourfold higher than the incidence in the unblinded period prior to the OLE and sixfold higher than the incidence observed in the blinded period [(incidence rates of 2 and 3 per 100 person-years, respectively)],” said principal investigator Dr Sinead Delany-Moretlwe from the University of the Witwatersrand in Johannesburg, South Africa.

Two-thirds of all pregnancies occurred in the active CAB-LA arm (n=212) at a median age of 28 years, followed by 68 pregnancies in the prior CAB-LA arm and 45 in the no CAB-LA arm at a median age of 27 years for both.

Of note, 75 percent of the participants in the active CAB-LA group had a history of STI diagnosis before pregnancy compared with 53 percent and 65 percent of those in the prior CAB-LA and no CAB-LA groups, respectively.

Maternal outcomes

Caesarean deliveries did not differ between groups, with 18 percent among those exposed to CAB-LA during and prior to pregnancy and 17 percent among those who were not exposed.

Similar rates of pregnancy-related grade ≥2 adverse events (AEs) were also observed at 38, 47, and 31 per 100 person-years in the active CAB-LA, prior CAB-LA, and TDF/FTC groups, respectively.

Gestational hypertension was the most common pregnancy-related AE, which was also similar across all groups.

None of the exposure groups reported maternal deaths or HIV infections during pregnancy.

Maternal weight gain (1 kg/month) was highest in the active CAB-LA group, but all pregnancy weight gain was within the excepted range.

The rates of spontaneous abortion (<20 weeks) did not differ between pregnancies exposed and unexposed to CAB (20 percent [active CAB-LA], 31 percent [prior CAB-LA], and 13 percent [no CAB-LA]). “However, it is important to interpret the spontaneous abortion data with caution, given the nonlegal status of termination of pregnancy in many HPTN 084 countries,” said Delany-Moretlwe.

The rates of composite poor pregnancy outcomes were also comparable in all groups (33 percent [active CAB-LA], 38 percent [prior CAB-LA], and 27 percent [no CAB-LA]). This result was mainly driven by the frequency of spontaneous abortion observed, Delany-Moretlwe noted.

Neonatal outcomes

A total of 223 live births were observed, 70 percent of which were those exposed to CAB-LA during pregnancy. The median gestational age at delivery (37–39 weeks) and birth weight (3 kg) were similar across all groups.

However, there were four neonatal deaths (1 case was associated with major congenital anomaly and 3 cases were due to respiratory distress) observed in the active CAB-LA group. None was reported in either the prior CAB-LA or no CAB-LA groups. Delany-Moretlwe noted that “all neonatal deaths were considered unrelated to PrEP by the investigators. The prevalence of neonatal deaths at around 2.5 percent is consistent with background rates of neonatal deaths, which can range from 1–4 percent in similar populations.”

“Overall, maternal, pregnancy, and infant outcomes were consistent across nonrandomized exposure groups and with expected background rates in similar populations,” said Delany-Moretlwe.