Abstract Body

HPTN 084 is a phase 3 randomized, double-blind, double-dummy trial that showed that long-acting injectable cabotegravir (CAB-LA) was superior to tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in preventing HIV in women in sub-Saharan Africa. Participants were required to use long-acting contraception; however, pregnancies occurred during the trial. We report on the safety and pharmacokinetics of CAB-LA in women who became pregnant in HPTN 084.

If a participant had a confirmed pregnancy, study injections were withheld and she was offered open-label TDF/FTC through pregnancy outcome and until cessation of breastfeeding, unblinded to study arm, and continued follow-up visits; live infants were assessed at birth and 12 months. Adverse events (AE) post-confirmation of pregnancy were compared between study arms. The apparent terminal phase half-life (t[sub]1/2app[/sub]) of CAB-LA in pregnant women in HPTN 084 was compared to non-pregnant women from HPTN 077, a phase 2 safety and pharmacokinetics study.

There were 49 confirmed pregnancies (29 CAB, 20 TDF/FTC) in 48 participants during the blinded phase of the study. Pregnancy incidence was 1.3 per 100 person-years (py). CAB-LA participants (n=6) experienced more pregnancy-related AE, including premature rupture of membranes (n=2), pre-eclampsia (n=1), oligohydramnios (n=1), incomplete abortion (n=1) and morning sickness (n=1) than TDF/FTC participants (morning sickness n=1). None of these AE were considered as product-related. No congenital anomalies were observed. Of the 43 participants (26 CAB-LA, 17 TDF/FTC) with confirmed pregnancy who received at least one injection, the incidence of ? grade 2 AEs in the CAB arm was 113/100 py (95% CI: 69.3-185.4/100 py) vs. 166/100 py (95% CI: 102.2-271.0/100 py) in the TDF/FTC arm (p=0.064). The CAB t1/2app geometric mean was 62.0 days (95% CI 43.7-88.0) for HPTN 084 pregnant women as compared to 64.3 days (95% CI: 51.1-80.8) in HPTN 077 non-pregnant women. Age, weight, race, and pregnancy status were not significantly associated with t1/2app. Body mass index (BMI) >27.2 kg/m2 was associated with a longer CAB t1/2app (fold-change: 1.49, 95% CI: 0.97-2.28; p=0.069).

Residual CAB-LA was generally well tolerated in pregnant women. The t1/2app was comparable between pregnant and non-pregnant women. Ongoing studies will examine the safety and pharmacology of CAB-LA in women who choose to continue CAB-LA through pregnan