Safety and Effectiveness of Isoniazid Preventive Therapy in Pregnant Women Living with Human Immunodeficiency Virus on Antiretroviral Therapy: An Observational Study Using Linked Population Data

Abstract Background Isoniazid preventive therapy (IPT) is widely used to protect against tuberculosis (TB) in people living with human immunodeficiency virus (HIV). Data on the safety and efficacy of IPT in pregnant women living with HIV (PWLHIV) are mixed. We used an individual-level, population-wide health database to examine associations between antenatal IPT exposure and adverse pregnancy outcomes, maternal TB, all-cause mortality, and liver injury during pregnancy through 12 months postpartum. Methods We used linked routine electronic health data generated in the public sector of the Western Cape, South Africa, to define a cohort of PWLHIV on antiretroviral therapy. Pregnancy outcomes were assessed using logistic regression; for maternal outcomes we applied a proportional hazards model with time-updated IPT exposure. Results Of 43 971 PWLHIV, 16.6% received IPT. Women who received IPT were less likely to experience poor pregnancy outcomes (adjusted odds ratio [aOR], 0.83 [95% confidence interval {CI}, .78–.87]); this association strengthened with IPT started after the first trimester compared with none (aOR, 0.71 [95% CI, .65–.79]) or with first-trimester exposure (aOR, 0.64 [95% CI, .55–.75]). IPT reduced the risk of TB by approximately 30% (aHR, 0.71 [95% CI, .63–.81]; absolute risk difference, 1518/100 000 women). The effect was modified by CD4 cell count with protection conferred if CD4 count was ≤350 cells/μL (aHR, 0.51 [95% CI, .41–.63]) vs 0.93 [95% CI, .76–1.13] for CD4 count >350 cells/µL). Conclusions This analysis of programmatic data is reassuring regarding the safety of antenatal IPT, with the greatest benefits against TB disease observed in women with CD4 count ≤350 cells/μL. Analysis of individual-level population-wide data is reassuring regarding the safety and efficacy of isoniazid preventive therapy to prevent tuberculosis disease in a cohort of >43 000 pregnant women living with HIV on antiretroviral therapy in South Africa.