Abstract
We investigated the predictors of plasma mid-dose concentrations (C12) of efavirenz by enrolling 456 HIV-positive patients who had received 2 nucleos(t)ide reverse-transcriptase inhibitors plus efavirenz (600 mg daily) for 2 weeks or longer and had their CYP2B6 516G>T polymorphism and efavirenz C12 determined. The median efavirenz C12 was 2.41 mg/L (IQR, 1.93–3.14). In analysis of covariance models, patients with CYP2B6 516GT and TT genotypes compared to those with GG genotype had higher efavirenz C12 (for GT genotype, an increase by 0.976 mg/L [95%CI, 0.765–1.188], and TT genotype, 4.871 mg/L [95%CI, 4.126–5.616]), while per 10-kg increment in weight decreased C12 by 0.199 mg/L (95%CI, 0.111–0.287). Models incorporating CYP2B6 516G>T polymorphism and weight had moderate predictive values in predicting efavirenz C12 ≥ 2 mg/L (ROC area under curve = 0.706 [95%CI, 0.656–0.756]). In the absence of CYP2B6 516G>T polymorphism, weight ≤58 kg provided better predictabilities for efavirenz C12 ≥ 2 mg/L (probability, 77.1% [95%CI, 69.0–83.5%] for weight = 50 kg and 70.6% [95%CI, 64.1–76.4%] for weight = 58 kg).
Highlights
The recommended EFV dose for an HIV-positive adult patient is 600 mg daily and the suggested therapeutic range of plasma mid-dose concentration (C12) of EFV is 1 to 4 mg/L
Be ameliorated by reductions of the EFV dose in areas where regimens consisting of EFV plus 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) remain the first-line combination antiretroviral therapy
Of the 502 HIV-positive patients receiving EFV-containing regimens during the study period, 456 patients (90.8%) were enrolled and 46 patients were excluded, including 14 whose plasma was sampled outside the time frame of 12 ± 2 hours after the last dose of EFV, 27 who were concurrently taking either rifampicin, anti-epileptics or protease inhibitors, and 5 who had documented poor drug adherence
Summary
The recommended EFV dose for an HIV-positive adult patient is 600 mg daily and the suggested therapeutic range of plasma mid-dose concentration (C12) of EFV is 1 to 4 mg/L. ENCORE1 study has shown that EFV at 400 mg daily is non-inferior to the standard 600 mg, when combined with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) in antiretroviral-naïve adult patients[9]. Under the scheme of therapeutic drug monitoring (TDM), successful reduction of EFV to a daily dose of 300 mg or 200 mg has been reported[21,22]. Considering that EFV in combination with TDF/FTC remains the first-line cART in areas where TDM is generally unavailable, HIV care providers may need other tools to guide dose reduction. Our previous study has shown that EFV dose reduction from 600 mg to 300 mg was associated with a 46.2% reduction in the plasma EFV C1223
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
