AEGiS-15IAC: Pharmacokinetics of nevirapine in HIV-HCV-coinfected patients.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Pharmacokinetics of nevirapine in HIV-HCV-coinfected patients.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. WeOrB1238)

Heripret L, Lavrut T, Durant J, Serini MA, Carsenti H, Dellamonica P, Garraffo R
Infectiology Unit, CHU, Nice, France

BACKGROUND: Nevirapine-associated hepatotoxicity is multifactorial, but HIV-HCV-coinfection is associated with a greater incidence of hepatotoxicity. Some reports suggest that this could be attributed partly to higher nevirapine plasma levels in coinfected patients. We compare the pharmacokinetics of nevirapine in HIV monoinfected and HIV-HCV coinfected patients.

METHODS: Prospective study including 10 HIV+HCV- and 10 HIV+HCV+ patients treated for more than 3 months with 2 NRTI and nevirapine. HIV+HCV+ patients had positive HCV PCR, serum ALT and AST< 2x upper limit of normal (ULN), when biopsy was available Metavir score ≤A1 and ≤F1, no previous HCV treatment. Nevirapine plasma levels were measured before ingestion and after 1, 2, 3, 4, 6, 8, 12 hours by HPLC. Pharmacokinetic parameters were determined using WinNonlin 3.2 software. Statistical analysis used variance analysis and Student test.

RESULTS: 20 patients were studied in each group: 10 men and 10 women. Median age was 40,5 yrs (IQR: 36,8-42,3), median weight was 68,5 kgs (59 - 77,5), median duration of nevirapine therapy was 38,5 mths (32,3-48,5). Both groups were comparable in age, weight, duration of nevirapine therapy, but they significantly differed in AST and ALT (0,74 vs 1,32 ULN and 0,84 vs 1,51 ULN, respectively, in HCV- vs HCV+ patients; p<0,05). [table: see text] There is no significant difference between both groups for Ctrough, Cmax, AUC and t1/2. Conclusion The greater incidence of severe nevirapine-associated hepatotoxicity in coinfected patients can not be attributed to higher plasma drug levels. The absence of difference between both groups demonstrates that nevirapine can be prescribed to coinfected patients with Mild Chronic Hepatitis at usual dosing regimen taking into consideration usual precautions of use.

Keywords: AEGIS, Nevirapine, HIV, Acquired Immunodeficiency Syndrome, HIV Seropositivity, HIV Infections, Hepacivirus, Anti-HIV Agents, Alanine Transaminase, Aspartate Aminotransferases, Incidence, HIV Antibodies, Therapeutic Equivalency, Prospective Studies, Humans, Female, Male, pharmacokinetics, immunology

040711
WeOrB1238