Fifth International Congress Drug Therapy in HIV Infection 22-26 October, 2000 Glasgow, UK

SEVERE LIVER TOXICITY IN PATIENTS RECEIVING TWO NUCLEOSIDE ANALOGUES AND A NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR

I. Sanne on behalf of the FTC-302 Study Investigators and the FTC-302 Independent Clinical Steering Committee
17. Eton Road, Parktown, Republic of South Africa 2193

Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL9.3
AIDS 2000, Oct 22-26;14(Suppl. 4); S12

The use of some antiretroviral agents has been associated with hepatotoxicity. This toxicity has been associated with concomitant chronic viral hepatitis, alcohol use, hypersensitivity reactions and lactic acidosis.

FTC-302 is a randomized, placebo-controlled, double-blind study comparing emtricitabine (FTC) to lamivudine 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.

A total of 468 patients were enrolled (385 in the NVP stratum, 83 in the EFV stratum). Fifty-nine percent of the patients are female; 87% of the patients are black. At the time of this report, all patients on treatment have completed 24 weeks. 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 4 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 two others had serological evidence of HCV infection. Incidence of grade 4 elevations was comparable between blinded treatment arms (9 versus 10%) and between blacks and non-blacks (9 versus 12%), but in females the incidence was twice that of males (12 versus 6%, P = 0.05). Two patients developed liver failure and died, one of whom was HBsAg positive at screening.

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 8 weeks of use.

Presenting author: I. Sanne

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2000-10-22
PL9-3

Originally published in AIDS Volume 14, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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