The V118I mutation as a marker of advanced HIV infection and disease progression

Mauro Zaccarelli, Valerio Tozzi, Patrizia Lorenzini, Federica Forbici, Pasquale Narciso, Francesca Ceceherini-Silberstein, Maria Paola Trotta, Ada Bertoli, Giuseppina Liuzzi, Patrizia Marconi, Silvia Mosti, Carlo Federico Perno, Andrea Antinori

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The V118I mutation is included in the nucleoside analogue mutations (NAMs) set. It contributes to thymidine-analogue resistance and, consequently, to resistance to the whole nucleoside reverse transcriptase inhibitor (NRTI) class. We focused on the V118I mutation in order to evaluate factors associated with its detection and its relationship with HIV progression. Methods: Clinical and laboratory data at genotypic resistance test (GRT) of highly active antiretroviral therapy-failing patients were collected and their association with the V118I mutation was analysed. Patients were also followed over time to determine factors related to progression to a new AIDS-related event or death. Results: Of the 792 patients included, 114 (14.4%) carried the V118I mutation. In univariate analysis, the V118I mutation was significantly associated with a higher HIV RNA level, lower CD4+ T-cell count, Centers for Disease Control and Prevention (CDC) stage C, higher number of pre-GRT regimens and class-wide resistance (CWR) to NRTIs, protease inhibitors and non-nucleoside reverse transcriptase inhibitors. Higher numbers of pre-GRT regimens and NRTI CWR were also associated in the multivariable analysis. Within the post-GRT observation period of up to 6 years (median: 72 months; interquartile range: 33-109) 107 events (58 new AIDS-related diseases and 49 deaths) were observed. Using the Cox proportional hazard model and the major clinical, behavioural and laboratory data, the V118I mutation was found to be associated with the endpoint (hazard ratio: 1.93, 95% confidence interval: 1.06-3.50; P=0.031). Other factors associated with disease progression were CDC stage C and lower CD4+ T-cell count at GRT. Conclusions: The analysis of our observational database suggests that the onset of the V118I mutation after treatment failure is unfavourable for the patient and can be considered a strong marker of disease progression.

Original languageEnglish
Pages (from-to)163-168
Number of pages6
JournalAntiviral Therapy
Volume12
Issue number2
Publication statusPublished - 2007

ASJC Scopus subject areas

  • Pharmacology

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