8th Conference on Retroviruses and Opportunistic Infections Chicago, IL - February 4 - 8, 2001

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:48 (abstract no. 19)

Bartlett J
Duke Univ, Durham, NC.

BACKGROUND: The use of specific antiretroviral agents may result in drug related hepatotoxicity. This toxicity has been associated with concomitant chronic viral hepatitis, alcohol use, hypersensitivity reactions and lactic acidosis.

METHODS: FTC-302 was a randomized, double-blind study comparing emtricitabine (FTC) to lamivudine (3TC) in a background of stavudine (d4T) and either nevirapine (NVP) (screening HIV-1 RNA ≤ 100,000 copies/mL) or efavirenz (EFV) (screening HIV-1 RNA >100,000 copies/mL) in antiretroviral treatment-naïve HIV-infected patients in the Republic of South Africa.

RESULTS: A total of 468 patients were enrolled (385 in the NVP stratum, 83 in the EFV stratum). Fifty-nine percent of the patients were female; 87% of the patients were black. At the time of this report, all patients on treatment have completed 24 weeks. Unblinded data through week 48 will be reported. To date, treatment-emergent grade 4 elevations in liver enzymes (ALT, AST, alkaline phosphatase, and total bilirubin) have been observed in 36 (9.4%) patients in the NVP stratum and in none of the patients receiving EFV. Of these 36 cases, 33 occurred within the first four weeks of therapy; the onset date for the remaining three cases was week 32. Of the 36 cases, one was HBsAg positive at screening with no evidence of active hepatitis, and 2 others had serological evidence of HCV infection. Incidence of grade 4 elevations was comparable between blinded treatment arms (9% vs. 12%), but in females the incidence was twice that of males (12% vs. 6%, p=0.05). Two patients developed liver failure and died, one of whom was HBsAg positive at screening.

CONCLUSIONS: In this study, a high incidence of severe liver toxicity was observed, especially in women. Clinically these events were attributed to NVP in combination with d4T and blinded treatment medication. Consistent with recent recommendations, liver enzymes in patients receiving NVP with other antiretrovirals should be monitored closely, particularly during the first eight weeks.

2001-02-04
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Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.