Fifth International Congress

Drug Therapy in HIV Infection


22-26 October, 2000
Glasgow, UK

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HEPATIC SAFETY WITH NEVIRAPINE (NVP) AND TWO NUCLEOSIDES IN PATIENTS WITH ADVANCED HIV INFECTION, FROM A PLACEBO (PBO) CONTROLLED CLINICAL ENDPOINT TRIAL (1090)

P. Cahn1, M. Johnson2, R. Nusrat3, D. Hall3, P. Robinson3 and the 31090 Study Team
1 Foundacion Huesped, Buenos Aires, Argentina; 2 Royal Free Hospital, London, UK; 3 Boehringer-Ingelheim Pharmaceuticals, Ridgefield, Connecticut, USA

Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL8.6
AIDS 2000, Oct 22-26;14(Suppl. 4); S11

BACKGROUND: Study 1090 was a clinical endpoint study of NVP versus PBO, in patients with advanced HIV infection. In addition to NVP or PBO all patients received at least two nucleoside analogues as background ARV therapy. This international trial was conducted from December 1995 through July 1998 and offers the opportunity to examine the incidence of hepatic adverse events (AEs) due to NVP and/or background therapies, in patients from diverse regions and ethnicities.

METHODS: Adult HIV infected patients with < 200 CD4+ cells were randomized to receive NVP or PBO, plus double nucleoside (nuc) background therapy. Patients were to remain on assigned therapy until a confirmed HIV endpoint occurred, and then could switch to open label NVP+ background therapy. All patients were to be followed for 24 months, regardless of changes in therapy. Clinical and laboratory safety and treatment exposure data were recorded prospectively and evaluated for the time when patients were on blinded NVP/PBO.

RESULTS: There were 2249 patients randomized to either NVP or PBO. The patients were from Western Europe (43%), North America (25%), South Africa (23%) and Argentina (8%). Women represented 20.8%; and 69.8% were white, 24.0% were black. The median time on blinded drug was about 13 months. Clinical hepatitis (including viral hepatitis) occurred in 2.8% and 1.4% of NVP and PBO patients (P = 0.026), respectively. Transaminase elevations > 5X ULN occurred in 8.2% of each group. One NVP and three PBO patients experienced fatal hepatic events (HEs); none were attributed to study medication. Approximately half of HEs appeared within the first 3 months, events continued to accumulate over the full duration of the study. Using Cox regression analysis, the only clear baseline factor predicting subsequent HEs (for both NVP and PBO groups) was elevated transaminases. Abnormal transaminases obtained while on study drug were poor predictors of subsequent HEs.

CONCLUSION: Hepatic events are encountered in HIV-infected patients taking NVP and non-NVP containing regimens. Understanding potential risk factors and clinically appropriate caution should help to minimize important HEs in patients receiving combination antiretroviral therapy.

Presenting author: P. Cahn

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2000-10-22
PL8-6

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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