Isoniazid Preventive Therapy and Pregnancy Outcomes In HIV-Infected Women in the Tshepiso Cohort

BACKGROUND: Both pregnancy and HIV increase the risk of tuberculosis disease which results in poor maternal, pregnancy, and infant outcomes. Isoniazid preventive therapy (IPT) reduces mortality among HIV-infected individuals in high-burden settings, but has recently been associated with adverse pregnancy outcomes when initiated during pregnancy. METHODS: In this secondary analysis, we used multivariable logistic regression to evaluate the association between IPT exposure and adverse pregnancy outcomes (fetal demise, prematurity, low birth weight and congenital anomaly) in HIV-infected pregnant women enrolled as controls in the Tshepiso study, a prospective observational cohort of HIV-infected pregnant women with and without TB disease in Soweto, South Africa from 2011-2014. RESULTS: There were 151 women enrolled with known pregnancy outcomes; 69 (46%) reported IPT initiation during pregnancy. Of the 69 IPT-exposed participants, 11 (16%) had an adverse pregnancy outcome compared to 23 of 82 (23%) IPT-unexposed participants. The adjusted odds of having an adverse pregnancy outcome was 2.5 (95%CI: 1.0, 6.5; p=0.048) times higher in IPT-unexposed women compared to IPT-exposed women after controlling for maternal age, CD4 count, viral load, antiretroviral regimen, body mass index and anemia. CONCLUSIONS: IPT exposure during pregnancy was not negatively associated with pregnancy outcomes after controlling for relevant demographic, clinical and HIV-related factors. These results may provide some reassurance that IPT can be safely used in the second or third trimester of pregnancy. Additional research is needed to confirm both the safety of IPT and new short-course TB preventive therapies during pregnancy.