BOSTON — Researchers reported that the immediate initiation of isoniazid preventive therapy for tuberculosis during pregnancy produced an unexpectedly high incidence rate of severe treatment-related adverse events among women with HIV. However, they said the rate was comparable to that among women who initiated therapy postpartum, suggesting that women should be given a choice of when to initiate therapy.
“Identifying ways to prevent TB during pregnancy and the postpartum period is a really important way to address maternal and infant health for a globally important disease such as tuberculosis,” Amita Gupta, MD, MHS, associate professor of medicine and international health and deputy director of the Center for Clinical Global Health Education at Johns Hopkins University School of Medicine, said during a press conference here.
At the Conference on Retroviruses and Opportunistic Infections, Gupta presented safety outcomes from a randomized, double-blind, placebo-controlled phase 4 trial in which they initiated isoniazid preventive therapy (IPT) during and after pregnancy in HIV-positive women on ART in TB-endemic areas of Africa, Asia and Haiti.
Immediate initiation of IPT began at 28 weeks antepartum and was compared with deferred initiation at 12 weeks postpartum. Randomization was arranged by gestational age. Every 4 weeks until week 48 postpartum, safety evaluations were performed on the mother-infant pairs to determine the primary safety outcome of treatment-related maternal adverse events greater than or equal to grade 3 or permanent discontinuation of treatment due to toxicity. The secondary outcomes were maternal hepatoxicity, maternal/infant death, TB, adverse pregnancy outcomes and infant adverse events, according to the presentation. The noninferiority margin was an incidence rate of five per 100 person-years.
Of the 956 women enrolled in the study, 171 discontinued the study prematurely. Results showed that 147 (15%) reached the primary outcome — 74 who initiated IPT antepartum and 73 who initiated IPT postpartum, with incidence rates 15.4 and 14.9 per 100 person-years, respectively. There were six deaths — two in antepartum arm and four in the postpartum arm. Of those deaths, three were due to treatment-related hepatotoxicity (one in the antepartum arm and two in the postpartum arm) and one nontreatment-related hepatotoxicity in the postpartum arm. No statistical difference in incidence rates of any maternal or infant adverse events of grade 3 or higher was found between the study arms. Similarly, there was no difference in maternal or infant TB by study arm. Adverse pregnancy outcomes were significantly higher for immediate initiation of IPT (23%) vs. deferred initiation (17%).
The researchers noted that although immediate and deferred initiation of IPT produced similar, yet unexpectedly high, incidence rates for the primary safety outcome, the prespecified noninferiority margin was not met, and TB incidence was low.
According to Gupta, a re-evaluation of the recommendation to initiate IPT during pregnancy in HIV-positive women on ART is needed.
“These data show that we have a low incidence of TB,” Gupta said, “so should we really be prioritizing IPT in pregnancy or give women the choice to know what the facts are and to select if they feel they want to take on IPT during pregnancy or defer it to after they deliver?” – by Marley Ghizzone
Gupta A, et al. Abstract 142LB. Presented at: Conference on Retroviruses and Opportunistic Infections; March 4-7, 2018; Boston.
Disclosure: Gupta reports no relevant financial disclosures.