Pharmacokinetic and pharmacodynamic analysis of amprenavir-containing combination therapy in HIV-1-infected children.

Several factors influence the antiviral response to antiretroviral therapy. In this pharmacokinetic and pharmacodynamic analysis, the relationship of drug exposure, demographics, and cotherapy measures to antiviral response in a cohort of largely treatment-experienced children treated with amprenavir and nucleoside reverse transcriptase inhibitors was examined. Multiple pharmacodynamic and demographic factors were examined, but only the minimum plasma concentration (C(min))/protein-binding-adjusted 50% inhibitory drug concentration (IC(50)) ratio and whether individuals received 2 versus fewer than 2 nucleosides to which their viral isolates were susceptible were associated with the magnitude of the time-weighted average change in HIV-1 RNA log(10) copies/mL from baseline (AAUCMB). In multivariate logistic regression analysis, only the C(min)/IC(50) ratio was independently associated with having a >or=1 log(10) AAUCMB decline. The probability in the study population of having a >or=1log(10) AAUCMB was 50% and 85% at C(min)/IC(50) ratios of approximately 1 and 4, respectively. Of the multiple factors examined, only the C(min)/IC(50) ratio was a significant predictor of antiviral response in the first 8 weeks on amprenavir-containing combination antiretroviral therapy.

RCT Entities:   Population Interventions Outcomes