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Antimicrobial Agents and Chemotherapy, August 2000, p. 2109-2117, Vol. 44, No. 8
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Prevalence and Characteristics of Multinucleoside-Resistant Human Immunodeficiency Virus Type 1 among European Patients Receiving Combinations of Nucleoside Analogues

Kristien Van Vaerenbergh,1,* Kristel Van Laethem,1 Jan Albert,2,dagger Charles A. B. Boucher,3 Bonaventura Clotet,4 Marco Floridia,5 Jan Gerstoft,6 Bo Hejdeman,7 Claus Nielsen,6 Christophe Pannecouque,1 Luc Perrin,8 Maria F. Pirillo,5 Lidia Ruiz,4 Jean-Claude Schmit,9 François Schneider,9 Anne Schoolmeester,10 Rob Schuurman,3 Hans J. Stellbrink,11 Lieven Stuyver,10 Jan Van Lunzen,11 Barbara Van Remoortel,1 Eric Van Wijngaerden,1 Stefano Vella,5 Myriam Witvrouw,1 Sabine Yerly,8 Erik De Clercq,1 Jan Desmyter,1 and Anne-Mieke Vandamme1

Rega Institute for Medical Research and University Hospitals, Leuven,1 and Innogenetics, Ghent,10 Belgium; Swedish Institute for Infectious Disease Control, Stockholm,2 and Stockholm Söder Hospital, Venhälsan,7 Sweden; University Hospital, Utrecht, The Netherlands3; Retrovirology Laboratory "irsi caixa", Badalona, Spain4; Istituto Superiore di Sanità, Roma, Italy5; Statens Serum Institut, Copenhagen, Denmark6; Laboratory of Virology, Geneva University Hospital, Geneva, Switzerland8; Laboratoire de Rétrovirologie, CRP-Santé, Luxembourg9; and Universitäts-Krankenhaus Eppendorf, Hamburg, Germany11

Received 28 December 1999/Returned for modification 13 March 2000/Accepted 25 April 2000

The prevalence and the genotypic and phenotypic characteristics of multinucleoside-resistant (MNR) human immunodeficiency virus type 1 (HIV-1) variants in Europe were investigated in a multicenter study that involved centers in nine European countries. Study samples (n = 363) collected between 1991 and 1997 from patients exposed to two or more nucleoside analogue reverse transcriptase inhibitors (NRTIs) and 274 control samples from patients exposed to no or one NRTI were screened for two marker mutations of multinucleoside resistance (the Q151M mutation and a mutation with a 2-amino-acid insertion at codon 69, T69S-XX). Q151M was identified in six of the study samples (1.6%), and T69S-XX was identified in two of the study samples (0.5%; both of them T69S-SS), but both patterns were absent among control samples. Non-NRTI (NNRTI)-related changes were observed in viral strains from two patients, which displayed the Q151M resistance pattern, although the patients were NNRTI naive. The patients whose isolates displayed multinucleoside resistance had received treatment with zidovudine and either didanosine, zalcitabine, or stavudine. Both resistance patterns conferred broad cross-resistance to NRTIs in vitro and a poor response to treatment in vivo. MNR HIV-1 is found only among multinucleoside-experienced patients. Its prevalence is low in Europe, but it should be closely monitored since it seriously limits treatment options.

* Corresponding author. Mailing address: Rega Institute for Medical Research and University Hospitals, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. Phone: 32 16 332160. Fax: 32 16 332131. E-mail: Kristien.vanvaerenbergh{at}uz.kuleuven.ac.be.

dagger Present address: Department of Clinical Virology, Huddinge University Hospital, Stockholm, Sweden.

Antimicrobial Agents and Chemotherapy, August 2000, p. 2109-2117, Vol. 44, No. 8
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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