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Antimicrobial Agents and Chemotherapy, June 2002, p. 1928-1933, Vol. 46, No. 6
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.6.1928-1933.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Jean Servais,^1* Christine Lambert,¹ Jean-Marc Plesséria,¹ Elodie Fontaine,¹ Isabelle Robert,¹ Vic Arendt,^1,2 Thérèse Staub,^1,2 Robert Hemmer,^1,2 François Schneider,^1,3 and Jean-Claude Schmit^1,2

Laboratoire de Rétrovirologie, Centre de Recherche Public-Santé,¹ Service National des Maladies Infectieuses, Centre Hospitalier de Luxembourg,² Laboratoire National de Santé, Luxembourg, Luxembourg³

Received 5 March 2001/ Returned for modification 14 June 2001/ Accepted 26 March 2002

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.

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* Corresponding author. Mailing address: Avenue de la gare 66, B-6840 Neufchâteau, Belgium. Phone: (32)61.277568. Fax: (32)61.227568. E-mail: jeanservais{at}hotmail.com.

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Antimicrobial Agents and Chemotherapy, June 2002, p. 1928-1933, Vol. 46, No. 6
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.6.1928-1933.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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