title: Treatment failure of nelfinavir-containing triple therapy can largely be explained by low nelfinavir plasma concentrations.
abstract: The 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, 1,250 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.
authors.affiliation: Department of Clinical Pharmacy, University Medical Center, Nijmegen, The Netherlands. D.Burger@klinfarm.azn.nl
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.forename: Patricia W H
authors.initials: PW
authors.lastname: Hugen
authors.forename: Rob E
authors.initials: RE
authors.lastname: Aarnoutse
authors.forename: Richard M W
authors.initials: RM
authors.lastname: Hoetelmans
authors.forename: Marielle
authors.initials: M
authors.lastname: Jambroes
authors.forename: Pythia T
authors.initials: PT
authors.lastname: Nieuwkerk
authors.forename: Gerrit
authors.initials: G
authors.lastname: Schreij
authors.forename: Margriet M E
authors.initials: MM
authors.lastname: Schneider
authors.forename: Marchina E
authors.initials: ME
authors.lastname: van der Ende
authors.forename: Joep M A
authors.initials: JM
authors.lastname: Lange
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods / Q000706:statistics & numerical data; D019540:Area Under Curve; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019888:Nelfinavir / Q000097:blood* / Q000627:therapeutic use*; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D017211:Treatment Failure
chemical_list: D019888:Nelfinavir