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 journalArticle

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

Fingerprint

HIV Infections
Disease Progression
Mutation
Reverse Transcriptase Inhibitors
Nucleosides
Centers for Disease Control and Prevention (U.S.)
CD4 Lymphocyte Count
Acquired Immunodeficiency Syndrome
HIV
T-Lymphocytes
Highly Active Antiretroviral Therapy
Protease Inhibitors
Treatment Failure
Proportional Hazards Models
Thymidine
Observation
Databases
RNA
Confidence Intervals

ASJC Scopus subject areas

  • Pharmacology

Cite this

The V118I mutation as a marker of advanced HIV infection and disease progression. / Zaccarelli, Mauro; Tozzi, Valerio; Lorenzini, Patrizia; Forbici, Federica; Narciso, Pasquale; Ceceherini-Silberstein, Francesca; Trotta, Maria Paola; Bertoli, Ada; Liuzzi, Giuseppina; Marconi, Patrizia; Mosti, Silvia; Perno, Carlo Federico; Antinori, Andrea.

In: Antiviral Therapy, Vol. 12, No. 2, 2007, p. 163-168.

Research output: Contribution to journalArticle

Zaccarelli, M, Tozzi, V, Lorenzini, P, Forbici, F, Narciso, P, Ceceherini-Silberstein, F, Trotta, MP, Bertoli, A, Liuzzi, G, Marconi, P, Mosti, S, Perno, CF & Antinori, A 2007, 'The V118I mutation as a marker of advanced HIV infection and disease progression', Antiviral Therapy, vol. 12, no. 2, pp. 163-168.
Zaccarelli, Mauro ; Tozzi, Valerio ; Lorenzini, Patrizia ; Forbici, Federica ; Narciso, Pasquale ; Ceceherini-Silberstein, Francesca ; Trotta, Maria Paola ; Bertoli, Ada ; Liuzzi, Giuseppina ; Marconi, Patrizia ; Mosti, Silvia ; Perno, Carlo Federico ; Antinori, Andrea. / The V118I mutation as a marker of advanced HIV infection and disease progression. In: Antiviral Therapy. 2007 ; Vol. 12, No. 2. pp. 163-168.
@article{0c7ac404fb824c52be9e5422db190760,
title = "The V118I mutation as a marker of advanced HIV infection and disease progression",
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.",
author = "Mauro Zaccarelli and Valerio Tozzi and Patrizia Lorenzini and Federica Forbici and Pasquale Narciso and Francesca Ceceherini-Silberstein and Trotta, {Maria Paola} and Ada Bertoli and Giuseppina Liuzzi and Patrizia Marconi and Silvia Mosti and Perno, {Carlo Federico} and Andrea Antinori",
year = "2007",
language = "English",
volume = "12",
pages = "163--168",
journal = "Antiviral Therapy",
issn = "1359-6535",
publisher = "International Medical Press Ltd",
number = "2",

}

TY - JOUR

T1 - The V118I mutation as a marker of advanced HIV infection and disease progression

AU - Zaccarelli, Mauro

AU - Tozzi, Valerio

AU - Lorenzini, Patrizia

AU - Forbici, Federica

AU - Narciso, Pasquale

AU - Ceceherini-Silberstein, Francesca

AU - Trotta, Maria Paola

AU - Bertoli, Ada

AU - Liuzzi, Giuseppina

AU - Marconi, Patrizia

AU - Mosti, Silvia

AU - Perno, Carlo Federico

AU - Antinori, Andrea

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34147170524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34147170524&partnerID=8YFLogxK

M3 - Article

C2 - 17503658

AN - SCOPUS:34147170524

VL - 12

SP - 163

EP - 168

JO - Antiviral Therapy

JF - Antiviral Therapy

SN - 1359-6535

IS - 2

ER -