Seventy-two percent of the 1995 enrollees were female; their median age was 32 years; their median CD4+ count was 297
, and 47% initiated ART during the 36-month period of observation. Of the 1436 women in the study, 721 (50.2%) were randomized to 6 months of IPT; 715 women (49.8%) were randomized to 36 months of IPT. A total of 268 pregnancies were observed during the trial. We excluded 29 women who were still pregnant at the time the dataset was closed or who exited the trial prior to the end of pregnancy, 23 repeat pregnancies, and 20 women without PMCT regimen data, leaving a total of 196 pregnancies in the analysis dataset (98 per arm). Some participants received placebo after 6 months of IPT or stopped taking isoniazid while remaining under observation in the trial, resulting in some women not receiving isoniazid while pregnant. Of women in the 6-month isoniazid arm, 20 were exposed to isoniazid during pregnancy, and 39 were exposed to ART. Of women in the 36-month isoniazid arm, 83 were exposed to isoniazid in pregnancy, and 34 were exposed to ART.
Overall, 103/196 (52.6%) women were exposed to isoniazid during some part of pregnancy, with 102 beginning in the first trimester, and 68% of these women had continuing exposure throughout pregnancy (). None of the women receiving isoniazid had severe hepatitis or rash either during pregnancy or in the postpartum period. Among these 103 women, 94 had begun isoniazid before pregnancy; the median duration of isoniazid receipt before the last menstrual period for these women was 341 days (range 1–1095 days).
Selected characteristics of subjects experiencing pregnancy during the Isoniazid Preventive Therapy Trial, Botswana, 2005–2008 (n = 196).
All women were exposed to antiretroviral drugs during pregnancy: 73 (37%) received ART, and the remainder received either short-course zidovudine (121) or zidovudine/lamivudine (AZT/3TC) (2). Of 73 women receiving ART during pregnancy, the most (64/73, 88%) received AZT/3TC and nevirapine; 3 received lopinavir/ritonavir-based regimens; 6 received other combinations. Women taking ART had significantly lower CD4+ T-cell counts than those taking short-course prophylaxis (median CD4+ count 239 versus 452, Wilcoxon rank-sum P < 0.0001). Of the 73 women receiving ART, 62% did so during all 3 trimesters. For the 47 women who began taking ART before pregnancy, the median duration of ART before pregnancy was 347 days (range 21–2221 days). Twenty-six initiated ART during pregnancy.
Two pregnant women developed TB symptoms during their pregnancies. One started anti-TB treatment 3 months after having a live birth, and the other initiated anti-TB treatment a month after her LNMP and sustained a stillbirth 7 months later. Both successfully completed standard 6-month anti-TB treatment.
Final outcomes of the 196 pregnancies were 124 (63%) term live births; 42 (21.4%) premature deliveries, 8 (4%) low-birth-weight term infants, 11 (6%) stillbirths, 6 spontaneous abortions (3%), 4 neonatal deaths (2%), and 1 congenital abnormality (talipes equinovarus, ).
In bivariate analysis (), ART receipt during pregnancy was associated with AO (unadjusted odds ratio (uOR) 2.0, 95% confidence interval (CI) 1.1–3.5), as was increasing maternal age (uOR 1.1 per year, 95%CI 1.0–1.1). Isoniazid exposure during pregnancy was not associated with increased odds of AO. Length of exposure to INH prior to pregnancy was also not associated with increased odds of AO when analyzed either as a continuous or categorical variable (data not shown).
Association between adverse pregnancy outcomes and isoniazid and/or antiretroviral therapy during pregnancy in HIV-infected women, Isoniazid Preventive Therapy Trial, Botswana, 2005–2008 (n = 196).
In a multivariable model including all variables in , none was significantly associated with increased odds of AO except maternal age. Addition of a dichotomous variable representing maternal CD4 count <200 near delivery did not significantly change any model parameter, and this variable was not retained. A separate but otherwise identical model showed no association between any variable (including ART exposure) and the outcome of preterm delivery (not shown). Similarly, another separate analysis with the same covariates but with the antiretroviral drug exposure variable dichotomized as exposure prior to pregnancy or in the first trimester versus all others demonstrated no significant association with preterm delivery (not shown).