4; 95% CI 1.5–7.8) (Table 2). Other baseline variables were not associated with the development

of rash-associated hepatotoxicity; these variables included CD4 cell count ≥250 cells/μL, age, BMI, HIV VL, concomitant anti-tuberculosis therapy and WHO ROCK inhibitor clinical stage. This analysis was repeated for each country separately and the same baseline transaminase association described above was observed (data not shown). CD4 count ≥250 cells/μL was not significantly associated with the development of rash-associated hepatotoxicity in any country but the association trended in different directions in Zambia (OR 0.5; 95% CI 0.01–3.8) and Thailand (OR 2.3; 95% CI 0.4–10.3). As abnormal baseline transaminases were a strong predictor of rash-associated hepatotoxicity, we also repeated this analysis excluding the 121 women with abnormal baseline transaminases. Among women with normal baseline transaminases (n=699), CD4 count ≥250 cells/μL was not associated with the development of rash-associated hepatotoxicity see more (OR 1.9; 95% CI 0.5–5.7). When we stratified baseline CD4 count by 50 cells/μL increments, women with the lowest CD4 counts (0–49 cells/μL) also had the highest rates (6.5%) of rash-associated hepatotoxicity (Fig. 2). However, rates of rash-associated hepatotoxicity also increased across the highest baseline CD4

count strata (200–249, 250–299 and ≥300 cells/μL) compared with women with baseline CD4 counts of 50–199 cells/μL (Cochran-Armitage trend test, P=0.004), suggesting a J-curve distribution of risk for rash-associated hepatotoxicity according to the CD4 count at which nevirapine-based ART was initiated. Compared with baseline CD4 counts of 50–199 cells/μL, a baseline CD4 count <50 cells/μL (aOR 3.7; 95% CI 1.0–13.5) and a baseline CD4 count ≥200 cells/μL (aOR 3.9; 95%

CI 1.3–12.6) were both associated with the development of rash-associated hepatotoxicity after adjusting Cobimetinib nmr for baseline transaminase levels and country. A similar association was not observed with CD4 cell count and severe hepatotoxicity or severe rash. Three women (0.4% of total participants) died with symptoms suggestive of fatal hepatotoxicity (Table 3). All three women had severe hepatotoxicity with additional symptoms (one woman also had rash-associated hepatotoxicity) and baseline CD4 counts <100 cells/μL, and were receiving anti-tuberculosis therapy. Two of these women were receiving four-drug anti-tuberculosis therapy that included rifampicin which had been prescribed by a nonstudy clinic unbeknown to the study clinician. Among women initiating nevirapine-based ART, severe hepatotoxicity and rash-associated hepatotoxicity were associated with elevated baseline transaminase levels. We did not observe an association for either severe hepatotoxicity or rash-associated hepatotoxicity with baseline CD4 count ≥250 cells/μL compared with CD4 count <250 cells/μL.