Abstract

The HEPADOSE study: evaluation of protease inhibitors and non nucleoside analogue plasma concentrations in HIV/HCV and HIV infected patients

Dominguez S.¹, Peytavin G.², Guiguet M.¹, Calvez V.¹, Costagliola D.¹, Bricaire F.¹, Poynard T.¹, Katlama C.¹, Benhamou Y.¹

¹Pitie salpetriere hospital,INSERM unity U720,University Pierre and Marie Curie, PARIS, France, ²Bichat Claude Bernard hospital, PARIS, France

Introduction: Whether HIV/HCV coinfection could impair drug metabolism remains unclear.

Methods: To compare plasma ARV concentrations in a cross sectionnal study we performed plasma ARV concentrations (Cmin) in HIV/HCV pts with a documented liver biopsy within two years matched on HIV pts according to sex and ARV. We used the standard threshold value to define the NNRTI and PI expected therapeutic concentrations . Statistical analysis was performed by using non parametric Wilcoxon test, or Fisher’s exact test.

Results: We enrolled 73 HIV/HCV and 66 HIV monoinfected pts, HIV RNA was < 200 cps/mL in 68% and 83 % pts ,median CD4 cell count was 331 and 385/mm3 respectively. Median PI Cmin were similar in the two groups, except for LPV wich was lower in HIV-HCV pts ( p=0.04). Both EFV and NVP Cmin were higher in HIV/HCV pts compared to HIV pts Moreover, according to the fibrosis stage NNRTI Cmin were significantly over the expected therapeutic concentration in HIV/HCV pts: 86% in F4 stage , 56% in F0-F3 stage compared to 24% in HIV pts (p=0.01). Among pts with NNRTI Cmin over the expected therapeutic concentration cytolysis ³ grade 2 was significantly more frequent in HIV/HCV pts compared to HIV pts (39% vs 10 % p=0.02).

ARV Cmin normal value(ng/ml)	VIH (n=66) n, Median Cmin ,range	VIH/VHC (n=73)n,Median Cmin ,range
Lopinavir (3000-7000)	[n=14] 5990 (4114-7920)	[n=16] 3673 (2535-4992) p=0.04
Ritonavir (400-1000)	[n=39] 373 (202-667)	n=47] 314 (161-646) p=0.62
Efavirenz (1100-3000)	[n=8] 1494 (1362-3083)	[n=12] 3583 (3270-4339) p=0.04
Nevirapine (3400-6000)	[n=13] 3954 (3461-4942)	[n=11] 5331 (3990-7326) p=0.12

Conclusions: In HIV/HCV patients Cmin did not change significantly for PI except for lopinavir, but NNRTI were strongly overdosed in HIV-HCV pts suggesting the need of drug monitoring in this population.