Influence of liver fibrosis stage on plasma levels of efavirenz in HIV-infected patients with chronic hepatitis B or C.
OBJECTIVE
Liver function is a key component of efavirenz metabolism and might be altered in severe liver fibrosis induced by HIV/chronic hepatitis co-infection. However, data evaluating the impact of liver fibrosis stages on the plasma efavirenz level are lacking.


METHODS
In this study, conducted in 134 HIV-infected patients [77, 35 and 22 HIV mono-infected, HIV/hepatitis C virus (HCV) co-infected and HIV/hepatitis B virus (HBV) co-infected, respectively] treated with efavirenz 600 mg once a day in combination with other antiretroviral agents, plasma concentration was measured at least 8 h after the last drug intake using a validated HPLC method. The degree of liver fibrosis was determined by means of either liver biopsy or non-invasive biochemical markers (Fibrotest. The proportions of patients above a threshold of 4000 ng/mL were compared by means of Pearson's chi(2) test or Fisher's exact test.


RESULTS
In HIV mono-infected and HIV/HCV and HIV/HBV co-infected patients, mean +/- SD efavirenz plasma concentrations were 3060 +/- 1928, 4108 +/- 3324 and 3163 +/- 2432 ng/mL, respectively. The proportion of patients with an efavirenz concentration above 4000 ng/mL differed significantly according to the presence of hepatitis and the fibrosis stage. A concentration above 4000 ng/mL was found in 14 patients (18.2%) mono-infected with HIV compared with 5 (22.7%, P = 0.01) and 9 (25.7%, P = 0.001) HIV/HBV or HIV/HCV co-infected patients, respectively. When the fibrosis stage was considered in all patients with hepatitis, 3 cirrhotic patients (42.6%) had an efavirenz concentration above the 4000 ng/mL threshold [compared with 14 (18.2%) HIV mono-infected patients, P = 0.001].


CONCLUSIONS
Therapeutic drug monitoring may be of interest in cirrhotic patients more at risk of side effects due to efavirenz overdosing.
Meynard
Jean-Luc
JL
Service des Maladies Infectieuses et Tropicales, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France. jean-luc.meynard@sat.ap-hop-paris.fr
Lacombe
Karine
K
Poirier
Jean-Marie
JM
Legrand
Jennifer
J
Morand-Joubert
Laurence
L
Girard
Pierre-Marie
PM
D000328:Adult; D000480:Alkynes; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000150:complications*; D019694:Hepatitis B, Chronic / Q000150:complications*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry*; D012720:Severity of Illness Index
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz