NIAID Now | October 03, 2019
Tuberculosis (TB) is the leading cause of death for people with HIV. Among women, TB predominantly affects people of childbearing age. When active TB disease develops during pregnancy or in the weeks after birth, it is associated with poor health outcomes for both the mother and baby.
The World Health Organization (WHO) strongly recommends providing the antibiotic isoniazid to prevent active TB in people with HIV. However, this recommendation is based upon data from nonpregnant adults. The safety, efficacy, and appropriate timing of TB preventive therapy with isoniazid in pregnant women, including women with HIV who are taking antiretroviral therapy (ART), has not been determined.
A clinical trial funded in part by NIAID, known as TB APPRISE, sought to fill this gap. The trial, which was conducted at 13 sites in 8 countries that have a high prevalence of TB, enrolled 956 women ages 18 years or older who were living with HIV and were between 14 and 34 weeks pregnant. The study participants were randomly assigned to a group that either began oral isoniazid during pregnancy (immediate group) or twelve weeks after giving birth (deferred group) and were followed 40 weeks post-birth.
The results showed a significant difference in pregnancy outcomes between the immediate and deferred groups. Among women taking isoniazid during pregnancy, 24% of pregnancies resulted in poor health outcomes for fetuses or newborns, including stillbirth, miscarriage, low birth weight, premature birth, or congenital abnormalities, compared with 17% in the deferred group.
Conversely, there was no difference in the rate of side effects experienced by women in the intermediate and deferred groups. Approximately 15% of women in both treatment groups suffered moderate-to-severe side effects as a result of isoniazid treatment. A total of six women—three in each group—developed TB.
Overall, women had an increased risk of serious adverse pregnancy outcomes when taking isoniazid during pregnancy versus after delivery, suggesting that alternative approaches to TB preventive therapy are needed in pregnant women. In addition, the trial highlights the need to include pregnant women in clinical trials to inform global health policy.
Reference: Gupta A et al. Isoniazid preventive therapy in HIV-infected pregnant and postpartum women. The New England Journal of Medicine. 2019 Oct. 3; 381(14):1333–46.