Pregnancy Outcomes in HIV-Infected Women Receiving Long-Term Isoniazid Prophylaxis for Tuberculosis and Antiretroviral Therapy

Abstract

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.

Trends in maternal deaths in HIV‐infected women, on a background of changing HIV management guidelines in South Africa: 1997 to 2015

“…Data from South Africa indicate poor uptake of isoniazid preventative therapy among HIV‐infected pregnant women . There have been concerns about the risk of hepatitis with isoniazid use in pregnancy, but available evidence suggests no increased risk even in pregnant women on ART receiving long‐term isoniazid .…”

Incidence and correlates of tuberculosis IGRA conversion among HIV-infected postpartum women

“…While universal isoniazid preventive therapy (IPT) is currently recommended for HIV-infected individuals, 37 the benefit of preventive therapy is most evident in those who are TST-positive. Although there are data to suggest that IPT is well tolerated in peripartum women in programmatic and trial settings, 38,39 there are still concerns about side effects in this population; this is the subject of a current National Institutes of Health-funded trial (IMPAACT P1078). An approach of repeated M. tuberculosis infection testing followed by IPT for those with a positive test without evidence of active TB may an alternative to universal IPT.…”

Preventing Tuberculosis Among HIV-Infected Pregnant Women in Lesotho

“…21,23 Our findings suggest that side effects with IPT during pregnancy are not commonly similar to reports from other studies in Botswana and Brazil, further strengthening the case for use during pregnancy. 14,[24][25][26][27] However, further studies are needed to assess the safety of this intervention, when administered in the context of a routine program in places with high HIV prevalence and concurrent use of ART, as this study was not specifically designed or powered to assess the safety of IPT in this context. In studies among the general adult population receiving isoniazid, less than 2% experience significant side effects.…”