Risk of failure in patients with 215 HIV-1 revertants starting their first thymidine analog-containing highly active antiretroviral therapy

Michela Violin, Alessandro Cozzi-Lepri, Rossella Velleca, Antonella Vincenti, Salvatore D'Elia, Francesco Chiodo, Florio Ghinelli, Ada Bertoli, Antonella D'Arminio Monforte, Carlo Federico Perno, Mauro Moroni, Claudia Balotta

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To investigate the impact of 215 HIV-1 revertants on the risk of virological failure of the first thymidine analog-containing highly active antiretroviral therapy (HAART). Design: The study included 491 HIV-1 subjects of the Italian Cohort Naive for Antiretrovirals, 405 of whom received a genotypic assay before therapy and had a virological follow-up. Methods: Pre-treatment genotypic resistance was assessed by sequencing of the whole protease (PR) and reverse transcriptase (RT) region. Results: Three (3.2%) and 13 (3.3%) individuals with recent (n = 95) and chronic (n = 396) HIV-1 infection carried an HIV-1 strain with 215 revertants (215D/C/E/A/V), respectively. In contrast, nucleoside associated mutations were higher in the former (15.8%) compared with the latter group (6.8%) (P = 0.005). A multivariable regression model, considering pre-HAART viral load levels, use of saquinavir-hard gel as the only PI, use of zidovudine, number of other RT and PR mutations, indicated that patients carrying 215 revenants had an increased risk of virological failure compared with those not carrying such mutants (adjusted relative hazard = 2.97 95% confidence interval, 1.11-7.94, P = 0.03). Among patients with 215 revenants, who experienced virological failure, four out of seven showed the emergence of the 215Y resistant mutation. The probability of 215Y occurrence was different between patients carrying 215 revenants compared with those who did not carried these mutants (P = 0.006). Conclusions: HIV-1 215 revertants with an increased ability for selecting 215Y mutation are associated with a higher risk of virological failure and may lead to the appearance of virus carrying 215Y/F mutation in vivo. These findings suggest that 215 revertant viruses may compromise the efficacy of the first thymidine analog-containing regimen.

Original languageEnglish
Pages (from-to)227-235
Number of pages9
JournalAIDS (London, England)
Volume18
Issue number2
DOIs
Publication statusPublished - Jan 23 2004

Keywords

  • 215 Revertants
  • HIV-1 genotypic resistance
  • Nucleoside-associated mutations

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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