Initiating 28-week isoniazid therapy during pregnancy was noninferior to initiating it 12 weeks after delivery to prevent tuberculosis in pregnant women with HIV who are on ART, according to results from a randomized controlled trial published in The New England Journal of Medicine. However, researchers found a greater risk for treatment-related adverse events in mothers who initiated treatment during pregnancy, suggesting that the best time to start isoniazid is after delivery.
Amita Gupta, MD, MHS, professor of medicine and international health in the division of infectious diseases and co-director of Center for Clinical Global Health Education at Johns Hopkins University, said WHO “currently strongly recommends” that adults and children with HIV receive isoniazid preventive therapy (IPT) for at least 6 months, including pregnant women, even though the recommendations are based on trials that excluded pregnant women.
“The WHO recommendation to initiate IPT during pregnancy in women with HIV who are on antiretroviral therapy needs re-evaluation,” she told Infectious Disease News.
Gupta and colleagues performed a multicenter, double-blind, placebo-controlled, noninferiority trial, during which pregnant women with HIV were randomly assigned to receive isoniazid preventive therapy for 28 weeks either during pregnancy or starting 12 weeks after delivery. They followed mothers and infants for 48 weeks after delivery.
Results showed that a primary outcome event — explained in the study as grade 3 or higher maternal treatment-related adverse events or permanent discontinuation of the trial regimen because of toxic effects — occurred in 72 of 477 women (15.1%) who initiated treatment during pregnancy (the immediate group) and in 73 of 479 (15.2%) women who initiated it 12 weeks after delivery (deferred group), a rate difference of 0.1 (95% CI, 4.77 to 4.98).
According to the study, two women in the immediate group and four women in the deferred group died, all during the postpartum period. Six women developed TB, three in each group. Unexpectedly, the researchers found there was a higher incidence of an adverse pregnancy outcome — including stillbirth or spontaneous abortion, low birth weight in an infant, preterm delivery or congenital anomalies in an infant — in the immediate group vs. the deferred group (23.6% vs 17%).
“In the first high quality [randomized controlled trial] ever done to study TB prevention in pregnant and postpartum women, the optimal timing of IPT initiation for pregnant women appears to be after delivery to avoid the increased adverse pregnancy outcomes and needs careful postpartum clinical monitoring and adherence support. The challenge is that many women are lost to follow-up in the postpartum period,” Gupta concluded.
“Programs have to weigh the risks of the increased adverse pregnant outcomes but ease of implementation of IPT initiation in pregnancy vs. the postpartum greater loss to follow-up and potential for never initiating TB prevention. Shorter, safer TB preventive regimens that have been recently identified need to be studied in pregnancy as we cannot assume data from nonpregnant populations is sufficient to inform policy for pregnant populations.” – by Caitlyn Stulpin
Disclosures: Gupta reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.