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.
Stein
Daniel S
DS
Worldwide Clinical Pharmacology, GlaxoSmithKline, Research Triangle Park, North Carolina, USA.
Lou
Yu
Y
Johnson
Mark
M
Randall
Sharon
S
Blanche
Stephane
S
D000293:Adolescent; D019380:Anti-HIV Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002219:Carbamates; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use
D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir