title: Longitudinal use of a line probe assay for human immunodeficiency virus type 1 protease predicts phenotypic resistance and clinical progression in patients failing highly active antiretroviral therapy.
abstract: An observational study assessed the longitudinal use of a new line probe assay for the detection of protease mutations. Probe assays for detection of reverse transcriptase (Inno-LiPA HIV-1 RT; Innogenetics) and protease (prototype kit Inno-LiPA HIV Protease; Innogenetics) mutations gave results for 177 of 199 sequential samples collected over 2 years from 26 patients failing two nucleoside reverse transcriptase inhibitors and one protease inhibitor (first line: indinavir, n = 6; ritonavir, n = 10; and saquinavir, n = 10). Results were compared to recombinant virus protease inhibitor susceptibility data (n = 87) and to clinical and virological data. Combinations of protease mutations (M46I, G48V, I54V, V82A or -F, I84V, and L90M) predicted phenotypic resistance to the protease inhibitor and to nelfinavir. The sum of protease mutations was associated with virological and clinical outcomes from 6 and 3 months on, respectively. Moreover, a poorer clinical outcome was linked to the sum of reverse transcriptase mutations. In conclusion, despite the limited number of patients studied and the restricted number of codons investigated, probe assay-based genotyping correlates with phenotypic drug resistance and predicts new Centers for Disease Control and Prevention stage B and C clinical events and virological outcome. Line probe assays provide additional prognostic information and should be prospectively investigated for their potential for treatment monitoring.
authors.affiliation: Laboratoire de Rétrovirologie, Centre de Recherche Public-Santé Service National des Maladies Infectieuses, Centre Hospitalier de Luxembourg. jeanservais@hotmail.com
authors.forename: Jean
authors.initials: J
authors.lastname: Servais
authors.forename: Christine
authors.initials: C
authors.lastname: Lambert
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Plesséria
authors.forename: Elodie
authors.initials: E
authors.lastname: Fontaine
authors.forename: Isabelle
authors.initials: I
authors.lastname: Robert
authors.forename: Vic
authors.initials: V
authors.lastname: Arendt
authors.forename: Thérèse
authors.initials: T
authors.lastname: Staub
authors.forename: Robert
authors.initials: R
authors.lastname: Hemmer
authors.forename: François
authors.initials: F
authors.lastname: Schneider
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Schmit
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D018450:Disease Progression; D004352:Drug Resistance, Microbial; D015658:HIV Infections / Q000188:drug therapy*; D016333:HIV Protease / Q000737:chemistry* / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D009154:Mutation; D010641:Phenotype; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D016333:HIV Protease