(C31) The effect of isoniazid use for tuberculosis prevention on pregnancy incidence among women living with HIV on antiretroviral treatment and progestin-based hormonal contraception
PhD student Gillings School of Global Public Health, University of North Carolina at Chapel Hill, United States
Background: Concomitant use of antiretroviral treatment (ART), hormonal contraception, and isoniazid for tuberculosis (TB) prevention is common among women of reproductive age who are living with HIV in sub-Saharan Africa – a region with high TB endemicity. A 6 or 9-month course of isoniazid for TB prevention is an essential prevention tool for women living with HIV in high TB burden areas. Isoniazid inhibits cytochrome P450 3A4, the primary hepatic enzyme responsible for metabolism of depot medroxyprogesterone acetate (DMPA) and the levonorgestrel (LNG) implant, and thus the potential for drug-drug interactions with these contraceptives exists.
Objectives: Our objective was to estimate the effect of isoniazid on 6-month pregnancy risk among women living with HIV who are taking either an efavirenz or dolutegravir-based ART regimen and using either DMPA or LNG implant contraception.
Methods: We analyzed data from the Family Planning and Antiretroviral Treatment (FP-ART) prospective cohort study. Women aged 18-40 years who were living with HIV in Malawi were recruited if they had recently initiated DMPA or the LNG implant. Eligible study visits were those with: reported ART use, DMPA or LNG implant use, no rifamycin antibiotic use, a negative urine pregnancy test, and an observed 6-month follow-up period post-visit. The exposure of interest, isoniazid use, was defined as any current isoniazid use self-reported at the study visit. The outcome of pregnancy was defined as an estimated conception date occurring 1-183 days (6 months) after the study visit. We conducted a visit-level analysis using inverse probability of treatment weights to adjust for the following confounders: age, breastfeeding status, education level at baseline, ART adherence, ART regimen type, and hormonal contraceptive type and adherence. We estimated the adjusted risk difference with a 95% confidence interval (95% CI) calculated using a robust standard error to accommodate multiple visits per participant.
Results: Among 6,721 FP-ART study visits, 4,881 visits (72.6%) from 1,177 women were eligible for inclusion in this analysis. There were 2,019 visits (41.4%) with reported isoniazid use. Pregnancy occurred during the 6-month follow-up period for 132 visits (2.7%); 70 among isoniazid use visits and 62 among non-use visits (3.5% vs 2.2%). The weighted 6-month risk of pregnancy among visits with isoniazid was 0.7 percentage points higher than the risk among non-use visits (95% CI: -0.6% to 2.0%).
Conclusions: We did not find a difference in 6-month pregnancy risk by isoniazid use in a cohort of women living with HIV who were concomitantly using ART and progestin-based contraception, which supports the continued safe use of isoniazid in this population.
