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Antimicrobial Agents and Chemotherapy, June 2001, p. 1836-1842, Vol. 45, No. 6
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.6.1836-1842.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Genotypic and Phenotypic Resistance Patterns of Human Immunodeficiency Virus Type 1 Variants with Insertions or Deletions in the Reverse Transcriptase (RT): Multicenter Study of Patients Treated with RT Inhibitors

Bernard Masquelier,1,* Esther Race,2 Catherine Tamalet,3 Diane Descamps,4 Jacques Izopet,5 Claudine Buffet-Janvresse,6 Annick Ruffault,7 Ali Si Mohammed,8 Jacqueline Cottalorda,9 Anne Schmuck,10 Vincent Calvez,11 Elisabeth Dam,2 Hervé Fleury,1 Françoise Brun-Vézinet,4 and the ANRS AC11 Resistance Study Group

The Virology Laboratories of the University Hospitals of Bordeaux,1 Marseille,3 Paris-Bichat Claude Bernard,4 Toulouse,5 Rouen,6 Rennes,7 Paris-Broussais,8 Nice,9 Grenoble,10 and Paris-Pitié Salpêtrière,11 and IMEA-INSERM, Hôpital Bichat Claude Bernard, Paris,2 France

Received 27 October 2000/Returned for modification 29 January 2001/Accepted 27 March 2001

Genomic rearrangements in the 5' part of the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have been involved in multidrug resistance to nucleoside RT inhibitors (NRTI). We carried out a retrospective, multicenter study to investigate the prevalence, variability, and phenotypic consequences of such rearrangements. Data concerning the HIV-1 RT genotype and the biological and clinical characteristics of NRTI-treated patients were collected from 10 virology laboratories. Sensitivities of the different HIV-1 variants to RT inhibitors were analyzed in a single-cycle recombinant virus assay. Fifty-two of 2,152 (2.4%) RT sequences had a rearrangement in the 5' part of the RT, with an extensive molecular variation. The number of codons inserted between positions 68 and 69 ranged from 1 (3 samples) or 2 (41 samples) to 5 and 11 in one case each. In four cases, codon 67 was deleted. High levels of phenotypic resistance to zidovudine (AZT), lamivudine (3TC), stavudine (d4T), abacavir (ABC), and didanosine (ddI) were found in 95, 92, 72, 62, and 15% of the 40 samples analyzed, respectively. Resistance to AZT, d4T, and ABC could be found in the absence of the T215Y/F mutations. Resistance to 3TC could develop in the absence of specific mutations. Low-level resistance to ddI was noticed in 40% of the patients. The deletions of codon 67 seemed to have little effect on NRTI sensitivity. Most of the rearrangements were shown to contribute to cross-resistance to NRTI. The results regarding susceptibility to ddI raise the question of the interpretation of the phenotypic data concerning this drug.

* Corresponding author. Mailing address: Laboratoire de virologie, Hôpital Pellegrin, Place Amélie Raba Léon, 33076 Bordeaux Cedex, France. Phone: 33 5 56 79 55 10. Fax: 33 5 56 79 56 73. E-mail: bernard.masquelier{at}chu-bordeaux.fr.

Antimicrobial Agents and Chemotherapy, June 2001, p. 1836-1842, Vol. 45, No. 6
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.6.1836-1842.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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