[44] ANALYSES OF FOUR KEY CLINICAL TRIALS TO ASSESS THE RISK OF HEPATOTOXICITY WITH NEVIRAPINE: CORRELATION WITH CD4<sup><font size="1" class="small">+</font></sup> LEVELS, HEPATITIS B & C SEROPOSITIVITY, AND BASELINE LIVER FUNCTIONS TESTS

1st International AIDS Society Conference on HIV Pathogenesis and Treatment

Buenos Aires, Argentina - July 8-11, 2001

[TITLE:] ANALYSES OF FOUR KEY CLINICAL TRIALS TO ASSESS THE RISK OF HEPATOTOXICITY WITH NEVIRAPINE: CORRELATION WITH CD4⁺ LEVELS, HEPATITIS B & C SEROPOSITIVITY, AND BASELINE LIVER FUNCTIONS TESTS

[AUTHOR(S):] Dieterich, D; Stern, J; Robinson, P; Hall, D; Carlier, H
Boehringer Ingelheim, Ridgefield, CT, USA

IAS Conf HIV Pathog Treat 2001 Jul 8-11;1st: Abstract No. 44

[ABSTRACT:] Objectives: To assess the incidence of nevirapine (NVP) hepatotoxicity as identifed by adverse events & evaluate markers that may predict increased risk for NVP hepatotoxicity.

Methods: Four NVP placebo controlled clinical trials (PBO) (n > 2700) were analyzed for liver related adverse events. Events were listed as the WHO preferred terms and were grouped as Hepatitis & Related Hepatic Events (HRHE).

Background: Prevalence of underlying liver disease is high among HIV study populations. Hepatotoxicity is a significant concern with ARTs and an important cause for discontinuation or disruption of therapy.

Results: In subjects with advanced HIV disease (n = 2249, median baseline CD4⁺ = 93) overall 1 yr rate of HRHE was NVP: 3.4%, PBO: 2.2% for a NVP attributable rate of 1.2%. In naïve subjects or those with limited prior ART exposure (n = 456, median baseline CD4⁺ = 363), the overall 1 yr rate of HRHE was NVP: 8.1%, PBO: 3.0% for a NVP attributable rate of 5.1%. Stratifying by baseline CD4⁺ < 350 (n = 203) the overall 1 yr rate of HRHE was NVP: 2.9%, PBO: 0% for a NVP attributable rate of 2.9%; while with CD4⁺ >= 350 (n = 253) the overall 1 yr rate of HRHE was NVP: 13.1%, PBO: 5.0% for a NVP attributable rate of 8.1%. Similar increased NVP HRHE risk factors include baseline ALT/AST >Grade 1 or co-infection with Hep B or C. Data from cohort studies will be presented to show the incidence of hepatic events in NVP treated patients is similar to that of patients treated with other ARTs.

Conclusions: Population based cohort studies have suggested the incidence of hepatic events in NVP treated patients is low. Observed rates in clinical trials appear to depend on several risk factors: baseline CD4⁺ >= 350 cells/mm3, baseline ALT/AST or co-infection with Hep B or C.

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