Pharmacodynamics of efavirenz 400mg in treatment-naïve Chinese HIV-infected patients in a prospective cohort study

Abstract

BackgroundThe plasma concentration of efavirenz (EFV) 600mg dose was found to exceed the upper limit of proposed therapeutic window in most Chinese HIV-infected individuals, thus dosage reduction of EFV to 400mg daily warrant consideration. This study aimed at assessing the pharmacodynamics of EFV 400mg for HIV-infected patients in China. MethodTwenty cART-naïve individuals were enrolled in this study. EFV 400mg combined with tenofovir (TDF) and lamivudine (3TC) as initial antiretroviral regimens were administered for 48 weeks. EFV concentration and T-cell subsets as well as HIV RNA load were evaluated at baseline, 4, 12, 24, 48 weeks. Moreover, the neuropsychiatric adverse effects were also assessed by Hamilton depression scale (HAMD) and Pittsburgh sleep quality index (PSQI).ResultsEighteen males and two females whose median age was 26 (interquartile range [IQR]: 23-32) years completed 48 weeks of follow-up. The median EFV concentration was 1.88 (IQR: 1.54-2.42), 1.74 (IQR: 1.36-1.93), 1.93 (IQR: 1.66-2.22), 1.85 (IQR: 1.54-2.14) mg/L at week 4, 12, 24, 48, respectively. The viral load was 4.59 (IQR: 4.10-5.19) lg copies/mL at baseline and it decreased by 4.6 (IQR: 3.98-5.18) lg copies/mL from baseline to weeks 48. 3 of 20 (15%), 10 of 20 (50.0%), 17 of 20 (85%), 18 of 19 (95%) participants had a plasma viral load less than 50 copies/mL at weeks 4, 12, 24, 48 respectively. The median CD4 cell count was 330 (IQR: 237-410) cells/µL at baseline and it increased to 473 (IQR: 344-574) cells/µL at 48 weeks. The score of HAMD was 5 (IQR: 3-9.8), 3 (IQR: 2.25-4) at baseline and 48 weeks. And the score of PSQI was 4 (IQR: 2-5.8), 3 (IQR: 2-4) at baseline and 48 weeks. Dizziness was the most common event, occurring in 70% patients within the first two weeks of treatment. ConclusionPatients prescribed with EFV 400mg-containing agents demonstrated favorable virological and immunological responses. And the plasma EFV concentration was within the recommended therapeutic range with less adverse reactions. EFV 400mg was effective and safe in Chinese HIV-infected patients.