Background:  Nevirapine (NVP), a pregnancy category B NNRTI, has been an important drug in the treatment of HIV⁺ women, particularly pregnant women. Increased risk of hepatotoxicity and rash has been reported in women with CD4 counts >250 cells/µl, usually during the first 18 weeks of treatment. It is unclear if NVP-associated adverse events are more common during pregnancy. This study aimed to identify the prevalence and predictors of adverse events associated with NVP use in a cohort of pregnant and non-pregnant women at 3 U.S. urban HIV clinics.

Methods:  This multi-center, retrospective cohort study included pregnant and non-pregnant HIV⁺ women aged 18 to 55 years, who initiated ART between 1999 and 2005. It compared NVP and non-NVP regimens for hepatic and rash adverse events occurring within 18 weeks ART initiation. Analyses were stratified by baseline CD4 cell count (>/≤250 cells/μL) and pregnancy status. Regimen comparisons were performed using χ² for dichotomous outcomes, and unpaired t-test or Mann-Whitney U tests for continuous variables.

Results:  Of 612 subjects, 27 had new hepatic events (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] ≥grade 2) documented:  6 of 140 (4.3%) in the NVP group compared to 21 of 459 (4.6%) in the non-NVP group (p = 0.885). No significant differences were observed in the development of ≥grade 3 hepatic adverse events between the NVP (n = 2, 1.4%) and non-NVP groups (n = 5, 1.1%, p = 0.668). Pregnancy was not an independent predictor of hepatotoxicity. However, women with nadir CD4 >250/μL were more likely to have hepatic events on a NVP-based regimen (p = 0.054) while women with CD4 ≤250/μL were more likely to have hepatic events on non-NVP regimens (p = 0.21). Among those with baseline CD4 ≤250/μL, there were no hepatic events in the NVP group and 16 (6.8%) in the non-NVP group (p = 0.13); of those with a baseline CD4 >250, 5.6% of the NVP group had hepatic events vs 2.3% in non-NVP (p = 0.255). Rashes ≥grade 2 were reported in 30 of 526 (5.7%), with a trend toward a higher frequency among women who initiated NVP-based regimens (p = 0.099). NVP was significantly associated with reports of ≥grade 2 rash among baseline CD4 counts ≥250 cells/µL (p = 0.001), with a trend among pregnant women (p = 0.054).

Conclusions:  This large cohort study confirms an increased risk of hepatotoxicity and rash when NVP is initiated in women with baseline CD4 >250 cells/μL. Although pregnancy was not an independent risk factor, all women with increased CD4 counts on NVP should be closely monitored for adverse events.