Emergence and genetic evolution of HIV-1 variants with mutations conferring resistance to multiple reverse transcriptase and protease inhibitors.

Abstract:

:The emergence of genotypic resistance in protease and reverse transcriptase (RT) gene regions was longitudinally evaluated in plasma samples from a group of 12 HIV-1-infected patients treated with different combination of antiretroviral therapies and selected on the basis of their clinical failure. Complex mutational patterns in the reverse transcriptase gene were observed. In particular, combinations of AZT (41L, 67N, 70R, 210W, and 219Q/E) and 3TC (184M) were seen in 10 patients. Two patients presented codon 151 multinucleoside analogue resistance (MNR). Additionally, seven patients harbored RT nonnucleoside analogue-related resistance substitutions (98G, 103N, and 181C). Multiple protease-selected mutations were found in each patient with an average of six substitutions per patient, with 10I/F/V, 63P, 71V, 82A/T, 84V, and 90M being the most prevalent substitutions. Overall, these results showed that for most patients virological failure was coupled with detectable genotypic resistance. Furthermore, most patients exhibited genotypic resistance to almost all available anti-HIV-1 drugs. The high viral loads found in most patients at the end of the study suggest that the replication of these multidrug resistant viruses are not severely compromised. Phylogenetic analysis of these pol sequences revealed that a specific HIV-1 genotype prone to develop multidrug resistance was not found.

journal_name

J Med Virol

authors

Cabana M,Clotet B,Martínez MA

doi

10.1002/(sici)1096-9071(199912)59:4<480::aid-jmv10

keywords:

subject

Has Abstract

pub_date

1999-12-01 00:00:00

pages

480-90

issue

4

eissn

0146-6615

issn

1096-9071

pii

10.1002/(SICI)1096-9071(199912)59:4<480::AID-JMV10

journal_volume

59

pub_type

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