Objective. While 6- to 12-month courses of isoniazid for tuberculosis prevention are considered safe in pregnant women, the effects of longer-term isoniazid prophylaxis or isoniazid in combination with antiretroviral therapy (ART) are not established in human-immunodeficiency-virus-(HIV-) infected women who experience pregnancy during the course of therapy. Design. Nested study of pregnancy outcomes among HIV-infected women participating in a placebo-controlled, TB-prevention trial using 36 months daily isoniazid. Pregnancy outcomes were collected by interview and record review. Results. Among 196 pregnant women, 103 (52.6%) were exposed to isoniazid during pregnancy; all were exposed to antiretroviral drugs. Prior to pregnancy they had received a median of 341 days (range 1–1095) of isoniazid. We observed no isoniazid-associated hepatitis or other severe isoniazid-associated adverse events in the 103 women. Pregnancy outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital abnormality. In a multivariable model, neither isoniazid nor ART exposure during pregnancy was significantly associated with adverse pregnancy outcome (adjusted odds ratios 0.6, 95% CI: 0.3–1.1 and 1.8, 95% CI 0.9–3.6, resp.). Conclusions. Long-term isoniazid prophylaxis was not associated with adverse pregnancy outcomes, such as preterm delivery, even in the context of ART exposure. 1. Introduction Tuberculosis (TB) is a major cause of morbidity and mortality for HIV-infected persons [1]. A clinical trial was recently completed in Botswana, in which a 36-month course of isoniazid prophylaxis against TB (IPT) was highly efficacious in reducing the risk of TB in tuberculin-skin-test-positive adults [2] when compared with a shorter-term regimen. Based upon this and other evidence [3], the World Health Organization recommended that in countries with high TB transmission, national health programs consider providing 36-month isoniazid prophylaxis for persons living with HIV [4]. The HIV epidemic disproportionately affects women in developing countries [5]. As availability of antiretroviral medications for therapy (ART) and for prevention of mother-to-child HIV transmission (PMTCT) has been rapidly scaled up [6], and with increasing health, pregnancy is common. While 6- to 12-month courses of isoniazid are considered safe in pregnancy [7], our objective was to describe the effects of longer-term isoniazid prophylaxis or simultaneous isoniazid and ART in pregnant HIV-infected women. 2. Methods
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