부산대학교 도서관

Background Once-daily nucleoside-sparing combination antiretroviral therapy (cART) regimens, such as maraviroc/darunavir/ritonavir, may be attractive therapeutic options. However, the pharmacokinetic (PK) profiles of such regimens have not been established. Methods HIV-1-infected subjects on stable cART comprising of tenofovir/emtricitabine (TDF/FTC) 245/200 mg plus darunavir/ritonavir 800/100 mg once daily with plasma HIV-1 RNA <50 copies/mL were eligible to enter this phase I, open-label, prospective, two-period PK study. On day 1 (period 1) maraviroc 150 mg daily was added to subjects cART regimen and on day 11 (period 2) TDF/FTC discontinued. At steady state (days 10 and 20) intensive PK sampling was undertaken. Geometric mean (GM) ratios for PK parameters between periods 2 versus 1 were calculated. In addition the number of subjects with trough (Ctrough) and average (Cave) maraviroc concentrations below 25 and 75 ng/mL (values previously associated with optimal virological response) were calculated and factors associated with total maraviroc exposure assessed. Results Eleven subjects completed study procedures with a mean age 49 years (range 35-59 years), 82% male and 27% and 73% of black and Caucasian ethnicity, respectively. Maraviroc GM (95% confidence interval [CI]) Ctrough and Cave concentrations in both study periods (see Table) were > 25 and > 75 ng/mL (concentrations associated with near maximal efficacy). No individual subjects had a maraviroc Cave below 75 ng/mL in either study period. One subject had a maraviroc Ctrough concentration below 25 ng/mL in period 1 (14 ng/mL) and one other subject in period 2 (21 ng/mL). Although no statistically significant differences in PK parameters were observed between period 2 and period 1 for any drug (see Table), a trend was observed towards lower maraviroc, darunavir and ritonavir concentrations in period 2 (TDF/FTC discontinued) versus period 1. [ABSTRACT FROM AUTHOR]