Among women with normal baseline transaminases (n=699), CD4 count ≥250 cells/μL was not associated with the development of severe hepatotoxicity (OR 1.3; 95% CI 0.4–3.3). We also stratified baseline CD4 count by 50 cells/μL increments (i.e. 0–49, 50–99, 100–149 cells/μL, etc.) to evaluate CD4 count associations not limited to the 250 cells/μL dichotomization. Women with the lowest CD4 counts (0–49 cells/μL) had the highest rates (7%) of severe hepatotoxicity (Fig. 2). Overall, women with baseline CD4 counts of Selleckchem HM781-36B 250–299 and ≥300 cells/μL had similar rates of severe hepatotoxicity to women in the lower CD4 count strata. Rash occurred in 148 women (18%) and

was severe (grade 3 or 4) in 23 cases (3%). The median onset time was 13 days (IQR 9.5–44 days) after initiating nevirapine and the median duration of rash was 17 days (IQR 10–28 days). Nevirapine was discontinued in all 23 women (58%) who had severe rash. One woman required hospitalization for severe rash (complications of Stevens–Johnson syndrome) but there were no deaths attributable to severe rash. Severe rash was associated with hepatotoxicity ≥grade 2 in six cases (26%). ART was reintroduced with a single drug substitution to either efavirenz (n=22) or ritonavir-boosted (100 mg dose) indinavir (n=1). Severe rash resolved and did not recur in 20 (91%) Navitoclax of

the 22 women who received efavirenz. Sclareol In two women severe rash persisted on efavirenz but

resolved with a single drug substitution to ritonavir-boosted lopinavir. Severe rash occurred in three (2%) of 121 women with a baseline CD4 count ≥250 cells/μL vs. 20 (3%) of 699 women with CD4 count <250 cells/μL (OR 0.9; 95% CI 0.2–3.0). Other baseline variables (including baseline transaminases, age, BMI, HIV VL, concomitant anti-tuberculosis therapy and WHO clinical stage) were not associated with the development of severe rash (data not shown). Rash-associated hepatotoxicity (any rash associated with hepatotoxicity ≥grade 2) occurred in 27 women (3%). Nevirapine was discontinued in 23 (85%) of 27 women with rash-associated hepatotoxicity. One of these women died with symptoms suggestive of fatal hepatotoxicity (discussed in detail below). ART was reintroduced in the other 22 women with either efavirenz (n=20) or ritonavir-boosted indinavir (n=2). Two participants who were restarted on efavirenz had to subsequently change to ritonavir-boosted indinavir because of persistent or worsening rash. Nevirapine was continued in four women with rash-associated hepatotoxicity because the rash and transaminase elevations had resolved on repeat clinical evaluation and testing. Rash-associated hepatotoxicity occurred in seven (6%) of 113 women with baseline abnormal (≥grade 1) ALT or AST vs. 20 (3%) of 699 women with normal baseline values (aOR 2.8; 95% CI 1.1–7.1) (Table 2).