In a study published by The New England Journal of Medicine today, Dr. Amita Gupta and colleagues found evidence to suggest that administering isoniazid preventive therapy (IPT) to prevent tuberculosis among HIV+ pregnant women who are taking antiretroviral therapy (ART) offered no benefits over beginning IPT at 12 weeks after delivery. Moreover, IPT during pregnancy is associated with higher adverse composite pregnancy events, including higher rates of low birth weight, preterm birth, stillbirth, and congenital anomalies. The World Health Organization’s guidelines for preventing TB in HIV+ pregnant women currently recommend isoniazid preventive therapy.

A multicenter, double-blind, placebo-controlled, non-inferiority trial was conducted that randomly assigned 956 HIV+ pregnant women to receive the current standard of care of a 28-week course of IPT, which was initiated either during pregnancy (immediate) or 12 weeks postpartum (deferred). Mother-infant pairs were then followed for 4 years. This trial was conducted in countries with high burden of both HIV and TB: South Africa, Zimbabwe, Uganda, Botswana, Tanzania, Thailand, India, and Haiti.

Researchers found that 23.6% of women who received IPT during pregnancy experienced adverse pregnancy outcomes, versus 17% for those who received IPT at 12 weeks postpartum—a statistically significant difference. There were no significant differences in adverse outcomes among the live-born infants followed in the study.

Although isoniazid has been around since the 1950s, this is the first randomized trial to study isoniazid preventive therapy in pregnant women, and the first trial to compare safety in initiating IPT during pregnancy with deferring administration until postpartum. WHO’s clinical care guidelines are based on data from non-pregnant populations. Pregnant women have been excluded from clinical trials; thus the safety, efficacy, and optimal timing of IPT for pregnant women receiving antitretroviral therapy for HIV are unknown.

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