Treatment failure of nelfinavir-containing triple therapy can largely be explained by low nelfinavir plasma concentrations

被引:57
作者
Burger, DM
Hugen, PWH
Aarnoutse, RE
Hoetelmans, RMW
Jambroes, M
Nieuwkerk, PT
Schreij, G
Schneider, MME
van der Ende, ME
Lange, JMA
机构
[1] Univ Med Ctr Nijmegen, Dept Clin Pharm, NL-6500 HB Nijmegen, Netherlands
[2] Slotervaart Hosp, Dept Pharm & Pharmacol, Amsterdam, Netherlands
[3] Univ Amsterdam, Dept Med Psychol, Amsterdam, Netherlands
[4] Univ Hosp, Maastricht, Netherlands
[5] Univ Utrecht, Ctr Med, Utrecht, Netherlands
[6] Univ Hosp, Rotterdam, Netherlands
关键词
pharmacokinetics; protease inhibitors; nelfinavir; virologic failure;
D O I
10.1097/00007691-200302000-00011
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
relationship between plasma concentrations of nelfinavir and virologic treatment failure was investigated to determine the minimum effective concentration of nelfinavir. Plasma samples were prospectively collected from treatment-naive patients who began taking nelfinavir, 1250 mg BID + two nucleoside reverse transcription inhibitors (NRTIs). Nelfinavir concentration ratios were calculated by dividing each individual nelfinavir level by the time-adjusted population value. Virologic failure was defined as either no response (a detectable viral load after 6 months) or a relapse (detectable viral load after being undetectable, or an increase in viral load >1 log above nadir). Forty-eight patients were included with a median follow-up period of 8 months. The median concentration ratio of nelfinavir was 0.98 (interquartile range, 0.76-1.47). Virologic failure was observed in 29% of the patients. In a univariate analysis, the nelfinavir concentration ratio appeared to be the single determinant that was related to virologic failure (P = 0.039). Patients with a median ratio <0.90 had a relative risk of 3.0 (95% CI, 1.2-7.6) for virologic failure. Using this threshold, virologic failures were detected with 64% sensitivity and 74% specificity (P = 0.014). Virologic failure of nelfinavir-containing triple therapy can be explained, to a large extent, by low plasma levels of nelfinavir.
引用
收藏
页码:73 / 80
页数:8
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