Aims To investigate the long‐term effects of efavirenz on cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein (LDL‐C) and triglycerides (TG). Methods Thirty‐four HIV‐infected patients who commenced efavirenz therapy were monitored for 36 months. Results In patients with baseline HDL‐C < 40 mg · dL−1 an increase in HDL‐C from 31 ± 1 mg · dL−1 to 44 ± 2 mg · dL−1 (95% confidence interval 5.9, 21.9, P < 0.01) was observed and remained throughout the follow‐up period. Median efavirenz plasma concentration was 1.98 mg · L−1 and a direct correlation between percentage of HDL‐C variation or TC/HDL‐C ratio and efavirenz plasma concentrations was found. Conclusions There is evidence of a long‐term and concentration‐dependent beneficial effect of efavirenz on HDL‐C in HIV‐infected patients.

Intrapatient variability in drug plasma concentrations is critical to the use of therapeutic drug monitoring with efavirenz, a non-nucleoside reverse-transcriptase inhibitor. Marked intrapatient variability, particularly for concentrations near the minimal therapeutic concentration, could be a predictor of virologic failure, meaning that a single concentration is of limited value. Previous reports on efavirenz intra-individual variability were obtained only in follow-up periods of 3 to 12 months and do not provide a rationale for the periodicity of sample measurements needed in long-term therapy to identify patients with a large variability and increased risk of therapeutic failure. The aim of this work was to investigate intra-individual variability in efavirenz plasma concentrations over a long-term follow-up period to support therapeutic drug monitoring. In a case series study, clinical and laboratory data were collected from all HIV-positive adults at the immunodeficiency outpatient clinic who were on regimens containing efavirenz in 2002 and who gave their informed consent (n = 31). Efavirenz plasma concentrations were measured throughout a 3 year period, without dose adjustments. For each patient, 6 to 12 samples were obtained over the follow-up period with an interval of at least 3 months between each sample. Mean plasma concentrations (mg/L) in the first, second, and third year of follow-up were 2.20 +/- 0.64, 2.17 +/- 0.68, and 2.31 +/- 0.57. Mean intra-individual variability throughout the first, second, and third year of study was 27%, 31%, and 25%, ranging from 12% to 63%. No differences in intrapatient variability in efavirenz plasma concentrations were found between females and males, HBV/HCV and HBV/HCV patients, or age above/below 40 years. Mean values (intra-individual variability) in plasma concentrations (mg/L) found in 3 of 31 patients who experienced virologic failure were 1.78 (42%), 1.52 (16%), and 1.68 (45%). The high interindividual variability and low maintained values of intrapatient variability in plasma concentrations support therapeutic drug monitoring, which could be based on measurements taken quarterly during the first year of therapeutics. In patients presenting high values of intra-individual variability (eg, >40%) associated with low plasma concentrations (eg, <2 mg/L), more frequent measurements over longer periods (more than 1 yr) of controlled concentrations might be recommended, but this requires further investigation.

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.