Suchergebnisse

IntroductionWide inter‐patient variation of plasma efavirenz (EFV) concentrations has been observed, and a substantial proportion of HIV‐positive patients may have unnecessarily higher plasma EFV concentrations than recommended while receiving EFV‐containing combination antiretroviral therapy (cART) at the currently recommended daily dose of 600 mg. A lower daily dose (400 mg) of EFV has recently been demonstrated to be as efficacious as the recommended 600 mg when combined with tenofovir/mtricitabine in a multinational clinical trial, with a lower incidence of adverse effects. We aimed to use a therapeutic drug monitoring (TDM)‐guided strategy to optimize the EFV dose in HIV‐positive Taiwanese patients.Materials and MethodsThe plasma EFV concentrations at 12 hours (C12) after taking the previous dose were determined among HIV‐positive adults who had received EFV‐containing cART with viral suppression (plasma HIV RNA load (PVL) <200 copies/mL). For those with EFV C12 >2.0 mg/L, EFV (Stocrit, MSD) was reduced to half a tablet daily. Determinations of EFV C12 were repeated 4–12 weeks after switch using high‐performance liquid chromatography. CYP2B6 G516T polymorphisms were determined using polymerase‐chain‐reaction restriction fragment‐length polymorphism.ResultsBetween April 2013 and June 2014, 111 patients (95.5% male; mean age, 39 years; 96.4% with PVL <40 copies/ml; 26.4% HBsAg‐positive and 7.5% anti‐HCV‐positive) with plasma C12 efavirenz >2.0 mg/L were switched to a reduced dose (1/2# hs) of EFV; 45.5% of them had CYP2B6 G516T or TT genotypes; and 32.4% weighed 60 kg or less. The mean baseline EFV C12 before switch was 3.65 mg/L (interquartile range (IQR), 2.62–4.17) for 111 patients, which decreased to 1.96 mg/L (IQR, 1.53–2.33) for 64 patients who had completed follow‐up of C12 EFV 4 weeks after switch, with a reduction of 49.4% (IQR, 38.9–57.0%). As of 10 July, 2014, all of the 38 patients (100%) who had completed at least one follow‐up of PVL achieved undetectable PVL (<40 copies/ml) following switch to a reduced dose of EFV after a mean observation of 13 weeks (IQR, 7–15 weeks).ConclusionsSwitch to cART containing a half tablet of EFV (1/2#) in HIV‐positive Taiwanese patients with higher plasma EFV concentrations who had achieved viral suppression could maintain successful viral suppression with the guidance of TDM.