1. Evaluation of long-acting cabotegravir safety and pharmacokinetics in pregnant women in eastern and southern Africa: a secondary analysis of HPTN 084.
- Author
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Delany-Moretlwe S, Hanscom B, Guo X, Nkabiito C, Mandima P, Nahirya PN, Mpendo J, Bhondai-Mhuri M, Mgodi N, Berhanu R, Farrior J, Piwowar-Manning E, Ford SL, Hendrix CW, Rinehart AR, Rooney JF, Adeyeye A, Landovitz RJ, Cohen MS, Hosseinipour MC, and Marzinke MA
- Subjects
- Humans, Female, Pregnancy, Adult, Young Adult, Africa, Eastern epidemiology, Pre-Exposure Prophylaxis, Africa, Southern epidemiology, Pregnancy Complications, Infectious drug therapy, Pregnancy Outcome, Tenofovir pharmacokinetics, Tenofovir adverse effects, Tenofovir therapeutic use, Tenofovir administration & dosage, Adolescent, Emtricitabine pharmacokinetics, Emtricitabine therapeutic use, Emtricitabine adverse effects, Emtricitabine administration & dosage, Diketopiperazines, Anti-HIV Agents pharmacokinetics, Anti-HIV Agents adverse effects, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, Pyridones pharmacokinetics, Pyridones adverse effects
- Abstract
Introduction: Long-acting injectable cabotegravir (CAB-LA) for pre-exposure prophylaxis significantly reduced HIV acquisition in HPTN 084. We report on the safety and CAB-LA pharmacokinetics in pregnant women during the blinded period of HPTN 084., Methods: Participants were randomized 1:1 to either active cabotegravir (CAB) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) placebo or active TDF/FTC plus CAB placebo. Pregnancy testing was performed at each visit; participants with a positive test had study product withheld and were offered open-label TDF/FTC. Pregnancies were confirmed on two tests at least 4 weeks apart. All participants with a positive pregnancy test prior to November 5, 2020 are included in this analysis. Pregnancy incidence, maternal adverse event (AE) incidence, pregnancy outcomes (including composite outcome of spontaneous abortion <20 weeks, intrauterine foetal death or stillbirth ≥20 weeks, premature birth <37 weeks, or small for gestational age) were assessed. The apparent terminal phase half-life (t
1/2app ) of CAB-LA in pregnant women in HPTN 084 was compared to non-pregnant women from the phase 2a HPTN 077 trial. Multivariable models assessed associations with t1/2app. RESULTS: Fifty-seven pregnancies (30 CAB-LA, 27 TDF/FTC) were confirmed over 3845 person-years [py] (incidence 1.5/100 py, 95% CI 1.1-1.9). CAB-LA group participants had a median 342 days (IQR 192, 497) of CAB-LA exposure prior to pregnancy detection. Grade 2 or higher maternal AE incidence did not differ by study arm (CAB 157, 95% CI 91-271 per 100 py vs. TDF/FTC 217, 95% CI 124-380 per 100 py; p = 0.256). Most pregnancies (81%) resulted in live births (25 CAB-LA, 22 TDF/FTC). Composite poor pregnancy outcomes did not differ significantly by group (CAB 6/30 vs. TDF/FTC 4/27; p = 0.476). No congenital anomalies were observed. The CAB t1/2app geometric mean was 52.8 days (95% CI 40.7-68.4) in pregnant women compared to 60.3 days (95% CI 47.7-76.3; p = 0.66) in non-pregnant women; neither pregnancy nor body mass index were significantly associated with t1/2app ., Conclusions: CAB-LA concentrations post-cessation of injections were 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 pregnancy and lactation., (© 2025 The Author(s). Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)- Published
- 2025
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