Safety of Short-course Weekly Rifapentine and Isoniazid (3HP) for TB Preventive Treatment at Conception and During First Trimester in Women With HIV: A Secondary Analysis of the WHIP3TB trial

Abstract Background The safety of a 3-month weekly rifapentine-isoniazid (3HP) for tuberculosis prevention in HIV-positive pregnant women on antiretroviral treatment is unknown. As part of the WHIP3TB trial, 3HP administered once or annually for 2 years was compared to 6 months of isoniazid. 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 ( Results Among 2207 women aged 15–49 years enrolled between November 2016 and November 2017, 236 pregnancies occurred in 222 participants. Fifty-seven (24%) were exposed to study drug (51 in 3HP arm, 6 in 6 months of isoniazid arm) and 179 were unexposed. Median age was 32 years, median antiretroviral treatment duration 2.9 years (interquartile range; 1.2–4.9 years) and median CD4 count 522 cells/L; [interquartile range, 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.