Safety of short-course weekly rifapentine and isoniazid (3HP) for TB preventive treatment at conception and during first trimester in women living with HIV: a secondary analysis of WHIP3TB trial

BACKGROUND: The safety of a 3-month weekly rifapentine-isoniazid (3HP) for tuberculosis prevention in HIV-positive pregnant women on antiretroviral treatment (ART) is unknown. As part of the WHIP3TB trial, 3HP administered once or annually for two years was compared to six months of isoniazid (6H). We report outcomes among women who became pregnant, with drug exposure in early pregnancy. METHODS: Women were classified as exposed if conception occurred while taking study drug, and unexposed if conception occurred after the last dose. Outcomes included live birth, stillbirth or abortion. A composite adverse pregnancy outcome was defined as any of the following: stillbirth, spontaneous abortion, low birth weight (<2500g), preterm delivery (<37 weeks gestation), or major congenital anomalies. Outcomes were compared between exposed and unexposed groups. RESULTS: Among 2207 women aged 15-49 years enrolled between November 2016-November 2017, 236 pregnancies occurred in 222 participants. Fifty-seven (24%) were exposed to study drug (51 in 3HP arm, 6 in 6H arm) and 179 were unexposed. Median age was 32 years, median ART duration 2.9 years (interquartile range [IQR]; 1.2-4.9 years) and median CD4 count 522 cells/L; [IQR, 345-684). Of 219 pregnancies with known outcomes, 162(74%) were live births, 51(23%) abortions and 6(3%) stillbirths. Spontaneous abortions occurred at similar frequencies among exposed (12% [7/57]) and unexposed (14% [22/162]) groups with comparable rates of composite adverse outcomes (33% [19/57] vs 35% [56/162]). CONCLUSIONS: Spontaneous abortion and composite adverse pregnancy outcomes, following first-trimester exposure to 3HP were comparable between exposed and unexposed groups, supporting the safety of 3HP in pregnancy.