Efavirenz concentrations in HIV‐infected patients with and without viral hepatitis

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • HIV‐1 co‐infection with HBV/HCV is the most important factor determining efavirenz‐induced liver toxicity. Higher efavirenz plasma concentrations have been reported in these patients facilitating concentration drug‐related adverse effects. • It is not known whether changes in efavirenz disposition are due to the hepatitis infection/inflammation or to liver failure. As a consequence, the guidelines for the application of therapeutic drug monitoring of efavirenz in HBV/HCV co‐infected patients have not been established. WHAT THIS STUDY ADDS • The present study has shown that HBV/HCV infection in itself does not predispose to higher efavirenz plasma concentrations. In the absence of hepatic failure, the risk of efavirenz concentration‐dependent toxicity is not increased. • Thus, therapeutic drug monitoring indications in co‐infected patients with hepatic function within the normal range should be the same as in HIV‐1 mono‐infected patients. AIMS Data on efavirenz in HIV/viral hepatitis co‐infected patients is non‐consensual, probably due to liver function heterogeneity in the patients included. METHODS A case control study was performed on 27 HIV‐infected patients, with controlled and homogenous markers of hepatic function, either mono‐infected or co‐infected with HBV/HCV, to ascertain the influence of viral hepatitis on efavirenz concentrations over a 2‐year follow‐up period. RESULTS No differences were found in efavirenz concentrations between groups both during and at the end of the follow‐up period: control (2.43 ± 1.91 mg l–1) vs. co‐infected individuals (2.37 ± 0.37 mg l–1). CONCLUSION It was concluded that HBV/HCV infections in themselves do not predispose to an overexposure to efavirenz.

Prospective plasma efavirenz concentration assessment in Chinese HIV‐infected adults enrolled in a large multicentre study

“…Prior studies have demonstrated high efavirenz concentrations among coinfected patients with cirrhosis, as a result of the impact of impaired liver function on efavirenz metabolism . No differences in efavirenz concentration have been reported in HBV‐ or HCV‐coinfected patients without cirrhosis when compared with HIV‐monoinfected patients ; however, one report showed a high efavirenz concentration in HCV‐monoinfected patients without liver cirrhosis . Patients with HBV or HCV infection in our study did not have cirrhosis.…”

Pharmacokinetics of the nonnucleoside reverse transcriptase inhibitor efavirenz among HIV‐infected Ugandans

“…The failure to find a significant influence of gender on efavirenz exposure, although such an influence has previously been reported [4,7], may have been a result of the skewed gender balance, as there were twice as many female as male participants. The effect of total bilirubin on efavirenz exposure previously reported [16] was not observed in this study; however, such a failure to observe any effect of parameters related to liver function has been documented before, and has been found in HIVinfected patients coinfected with hepatitis [25,26].…”

Pharmacokinetics and Pharmacodynamics of the Non-Nucleoside Reverse-Transcriptase Inhibitor Etravirine in Treatment-Experienced HIV-1-Infected Patients

“…Other NNRTIs have shown similar increases in hepatitis C coinfected patients, although conflicting data exist with respect to both efavirenz and nevirapine. 20 , 21 , 22 , 23 , 24 The change in the apparent oral clearance of etravirine was negligible (+8.3%) in subjects with hepatitis B coinfection, and a 24% decrease was observed in subjects with hepatitis C coinfection. The importance of this finding is limited by the relatively small number of patients with hepatitis B and/or C coinfection and by the exclusion of coinfected patients with markedly elevated liver enzymes.…”