618   Hepatotoxicity Associated with NNRTI Use: Role of Drugs and Chronic Viral Hepatitis.

M. Sulkowski*, S. Mehta, D. Thomas, and R. Moore.
Johns Hopkins Univ., Baltimore, MD.

Background:The use of HARRT regimens that include NNRTIs has been associated with hepatotoxicity, particularly among HCV- or HBV-coinfected pts. The objectives of this study were to compare the incidence of severe hepatotoxicity associated with efavirenz (EFV)- and nevirapine (NVP)-containing regimens and to define the role of chronic viral hepatitis in its development.

Methods:298 pts. prescribed a new NNRTI-containing regimen (NVP, 202 pts and EFV, 96 pts) were prospectively followed in the Johns Hopkins HIV clinic cohort. AST and ALT levels were evaluated before and during drug therapy, and severe hepatotoxicity was defined as grade 3 or 4 changes according to standard toxicity criteria (JAMA283:74, 2000). HCV and HBV serologies were routinely performed on all pts.

Results:Pts. prescribed NVP were more likely to be black (79% > 66%), to be HBsAg reactive (9% > 2%) and to have HIV load >10, 000 c/mL (76% > 63%) than those prescribed EFV, but no differences were observed in age, sex, IDU status, HCV⁺status (49% NVP/45%EFV), and baseline levels of AST, ALT, or CD4 cells. The median duration of follow-up was 280 (IQR 121—619) days for NVP users and 167 (IQR 95 — 286) days for EFV users. Severe hepatotoxicity was observed in 41 (13.8%) of NNRTI users (95% CI 10.1—18.2), including 33 (16.7%) of 202 NVP users (95% CI 11.5—22.0%) and 8 (8.3%) of 96 EFV users (95% CI 3.7—15.7). The incidence rate (cases/100 person-months) of severe hepatotoxicity was similar for NVP [1.3 (95% CI 0.9—1.8)] and EFV users [1.2 (95% CI 0.6—2.4)]. Chronic HCV or HBV was not associated with an increased risk of severe toxicity (RR 1.2, 95% CI 0.65—2.06). In multivariate regression analysis, only CD4 increase >50/mm³[OR 2.5 (95% CI 1.2—4.5)] was associated with hepatotoxicity in NNRTI recipients.

Conclusions:Although significantly more hepatotoxicity was observed among NVP users, due to greater time on NVP, only CD4 cell increase was independently associated with severe hepatotoxicity. Since the incidence of severe hepatotoxicity was not increased in patients with chronic HCV or HBV infection, these data indicate that NNRTI therapy should not be withheld from patients with chronic viral hepatitis.