[TuPeB4534] Low Incidence of Grade III/IV Hepatotoxicity in First HAART: Observations from 1100 Patients Followed for 1 Year

14th International AIDS Conference

Barcelona, Spain — July 7-12, 2002

[TITLE:] Low Incidence of Grade III/IV Hepatotoxicity in First HAART: Observations from 1100 Patients Followed for 1 Year

[AUTHOR(S):] D.T. Dietrich¹, S.L. Becker², J.S. Fusco, R.B. Balu, B.M. Most, G.P. Fusco³, J. Stern, S. Lanes⁴

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. TuPeB4534

BACKGROUND: Hepatotoxicity (HT) has emerged as a major complication of ART and limits the use of antiretroviral agents. HBV and HCV coinfection have been identified as risk factors. The incidence of HT among various classes of ART remains unclear. This analysis evaluates HT in patients during their first HAART regimen from the CHORUS cohort.

Methods and Results: Patients were categorized into mutually exclusive groups: NRTIs only (n=191), NRTIs+PIs (n=559), NRTIs+NNRTIs (n=284) or triple class therapy (n=84). Prevalence of HBV/HCV was 33.0%/11.5%. HT was defined as a diagnosis of clinical hepatitis, bili >3.5, or AST/ALT >5X ULN. At baseline the NRTI only group had more African Americans, females, IDUs, lower viral load, and higher CD4 count. The triple class group was more likely to have HBV/HCV and elevated LFTs at baseline. The rate of grade 3+HT was 5.5%, no patient had a diagnosis of clinical hepatitis. The low rate of grade 3+HT precluded modeling with control for multiple risk factors therefore HT was modified to include grade 2 AST/ALT(>2.5X ULN), representing 49.2% of events. The unadjusted rate(r) and median time(t) to grade 2+HT were; NRTI only (r=7.8%, t=64 days), NRTI+PI (r=12.2%, t=98 days), NRTI+NNRTI (r=9.2%, t=136 days), and triple class (r=10.7%, t=160 days). In multivariable logistic regression analyses including age, gender, race, site, prior AIDS diagnosis, route of infection, BL LFTs, past HBV/HCV, concurrent hepatitis, ART prior to HAART (mono/dual) and alcohol use; elevated BL LFTs (OR=3.1; CI:2.1, 4.6; p<0.0001), concurrent hepatitis (OR= 4.9; CI:2.9, 8.5; p<0.0001), and past HBV/HCV (OR=2.2; CI:1.5, 3.4; p=0.0002) were the most significant predictors of HT. Only NRTI+PI had a marginal association with hepatotoxicity (OR=1.5; CI:1.0, 2.2; p=0.0554) compared to NRTI only.

CONCLUSIONS: Laboratory and clinical HT occurred at a low rate in all classes. Coinfection with HBV or HCV and BL elevated LFTs were associated with increased risk of HT.

Presenting author: Jennifer Fusco

1Liberty Medical LLP, GlaxoSmithKline, PO Box 13398, Research Triangle Park, NC 27709-3398, United States.

2Pacific Horizon Med Group, San Francisco, United States.

3GlaxoSmithKline, RTP, United States.

4Boehringer-Ingelheim, Ridgefield, United States.

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