Effects of drug resistance on viral load in patients failing antiretroviral therapy

N. Machouf, R. Thomas, V. K. Nguyen, B. Trottier, M. R. Boulassel, M. A. Wainberg, J. P. Routy

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Previous studies on patients who develop drug resistant HIV-1 variants have shown that continued use of failing regimens might provide clinical benefit. However, the effect of long-term exposure to drug resistant variants may lead to emergence of compensatory mutations that may jeopardize this effect. In this study, we assess associations among type and number of drug resistant mutations, viral load and disease progression in patients with long-term follow up. Patients with genotypic testing performed at the time of treatment failure were enrolled. Comparison of viral load and CD4 cell count between different resistance groups was performed using analysis of variance. Multiple linear regression analysis was performed to assess the simultaneous effects of the presence of particular mutations and their accumulation on viral load. Data from 475 patients who were followed for a median of 43 months from October 1999 to July 2005 were studied. A "V shape" relationship was observed between the number of mutations and viral load. Specifically, in patients harboring up to five mutations, viral load was reduced by 0.8 log/copies when compared to wild-type variants. However, with more than six mutations viral load progressively increased. Certain reverse transcriptase mutations such as M184V/I, K70R, V108I, and protease mutations such as L33FIV, M84V, and M36I were associated with reduced viral load. Together, these findings suggest that long-term maintenance of a sub-optimal antiretroviral regimen may have deleterious consequences for the patient.

Original languageEnglish
Pages (from-to)608-613
Number of pages6
JournalJournal of Medical Virology
Volume78
Issue number5
DOIs
Publication statusPublished - May 2006

Fingerprint

Viral Load
Drug Resistance
Mutation
Therapeutics
Pharmaceutical Preparations
RNA-Directed DNA Polymerase
Virus Diseases
CD4 Lymphocyte Count
Treatment Failure
Disease Progression
HIV-1
Linear Models
Analysis of Variance
Peptide Hydrolases
Regression Analysis

Keywords

  • Antiretroviral drug failure
  • Drug resistance
  • Genotypic testing
  • HIV
  • V-shape relationship

ASJC Scopus subject areas

  • Virology

Cite this

Machouf, N., Thomas, R., Nguyen, V. K., Trottier, B., Boulassel, M. R., Wainberg, M. A., & Routy, J. P. (2006). Effects of drug resistance on viral load in patients failing antiretroviral therapy. Journal of Medical Virology, 78(5), 608-613. https://doi.org/10.1002/jmv.20582

Effects of drug resistance on viral load in patients failing antiretroviral therapy. / Machouf, N.; Thomas, R.; Nguyen, V. K.; Trottier, B.; Boulassel, M. R.; Wainberg, M. A.; Routy, J. P.

In: Journal of Medical Virology, Vol. 78, No. 5, 05.2006, p. 608-613.

Research output: Contribution to journalArticle

Machouf, N, Thomas, R, Nguyen, VK, Trottier, B, Boulassel, MR, Wainberg, MA & Routy, JP 2006, 'Effects of drug resistance on viral load in patients failing antiretroviral therapy', Journal of Medical Virology, vol. 78, no. 5, pp. 608-613. https://doi.org/10.1002/jmv.20582
Machouf, N. ; Thomas, R. ; Nguyen, V. K. ; Trottier, B. ; Boulassel, M. R. ; Wainberg, M. A. ; Routy, J. P. / Effects of drug resistance on viral load in patients failing antiretroviral therapy. In: Journal of Medical Virology. 2006 ; Vol. 78, No. 5. pp. 608-613.
@article{d4a8d115f7374105a67547ce8abf70f3,
title = "Effects of drug resistance on viral load in patients failing antiretroviral therapy",
abstract = "Previous studies on patients who develop drug resistant HIV-1 variants have shown that continued use of failing regimens might provide clinical benefit. However, the effect of long-term exposure to drug resistant variants may lead to emergence of compensatory mutations that may jeopardize this effect. In this study, we assess associations among type and number of drug resistant mutations, viral load and disease progression in patients with long-term follow up. Patients with genotypic testing performed at the time of treatment failure were enrolled. Comparison of viral load and CD4 cell count between different resistance groups was performed using analysis of variance. Multiple linear regression analysis was performed to assess the simultaneous effects of the presence of particular mutations and their accumulation on viral load. Data from 475 patients who were followed for a median of 43 months from October 1999 to July 2005 were studied. A {"}V shape{"} relationship was observed between the number of mutations and viral load. Specifically, in patients harboring up to five mutations, viral load was reduced by 0.8 log/copies when compared to wild-type variants. However, with more than six mutations viral load progressively increased. Certain reverse transcriptase mutations such as M184V/I, K70R, V108I, and protease mutations such as L33FIV, M84V, and M36I were associated with reduced viral load. Together, these findings suggest that long-term maintenance of a sub-optimal antiretroviral regimen may have deleterious consequences for the patient.",
keywords = "Antiretroviral drug failure, Drug resistance, Genotypic testing, HIV, V-shape relationship",
author = "N. Machouf and R. Thomas and Nguyen, {V. K.} and B. Trottier and Boulassel, {M. R.} and Wainberg, {M. A.} and Routy, {J. P.}",
year = "2006",
month = "5",
doi = "10.1002/jmv.20582",
language = "English",
volume = "78",
pages = "608--613",
journal = "Journal of Medical Virology",
issn = "0146-6615",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Effects of drug resistance on viral load in patients failing antiretroviral therapy

AU - Machouf, N.

AU - Thomas, R.

AU - Nguyen, V. K.

AU - Trottier, B.

AU - Boulassel, M. R.

AU - Wainberg, M. A.

AU - Routy, J. P.

PY - 2006/5

Y1 - 2006/5

N2 - Previous studies on patients who develop drug resistant HIV-1 variants have shown that continued use of failing regimens might provide clinical benefit. However, the effect of long-term exposure to drug resistant variants may lead to emergence of compensatory mutations that may jeopardize this effect. In this study, we assess associations among type and number of drug resistant mutations, viral load and disease progression in patients with long-term follow up. Patients with genotypic testing performed at the time of treatment failure were enrolled. Comparison of viral load and CD4 cell count between different resistance groups was performed using analysis of variance. Multiple linear regression analysis was performed to assess the simultaneous effects of the presence of particular mutations and their accumulation on viral load. Data from 475 patients who were followed for a median of 43 months from October 1999 to July 2005 were studied. A "V shape" relationship was observed between the number of mutations and viral load. Specifically, in patients harboring up to five mutations, viral load was reduced by 0.8 log/copies when compared to wild-type variants. However, with more than six mutations viral load progressively increased. Certain reverse transcriptase mutations such as M184V/I, K70R, V108I, and protease mutations such as L33FIV, M84V, and M36I were associated with reduced viral load. Together, these findings suggest that long-term maintenance of a sub-optimal antiretroviral regimen may have deleterious consequences for the patient.

AB - Previous studies on patients who develop drug resistant HIV-1 variants have shown that continued use of failing regimens might provide clinical benefit. However, the effect of long-term exposure to drug resistant variants may lead to emergence of compensatory mutations that may jeopardize this effect. In this study, we assess associations among type and number of drug resistant mutations, viral load and disease progression in patients with long-term follow up. Patients with genotypic testing performed at the time of treatment failure were enrolled. Comparison of viral load and CD4 cell count between different resistance groups was performed using analysis of variance. Multiple linear regression analysis was performed to assess the simultaneous effects of the presence of particular mutations and their accumulation on viral load. Data from 475 patients who were followed for a median of 43 months from October 1999 to July 2005 were studied. A "V shape" relationship was observed between the number of mutations and viral load. Specifically, in patients harboring up to five mutations, viral load was reduced by 0.8 log/copies when compared to wild-type variants. However, with more than six mutations viral load progressively increased. Certain reverse transcriptase mutations such as M184V/I, K70R, V108I, and protease mutations such as L33FIV, M84V, and M36I were associated with reduced viral load. Together, these findings suggest that long-term maintenance of a sub-optimal antiretroviral regimen may have deleterious consequences for the patient.

KW - Antiretroviral drug failure

KW - Drug resistance

KW - Genotypic testing

KW - HIV

KW - V-shape relationship

UR - http://www.scopus.com/inward/record.url?scp=33645943739&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645943739&partnerID=8YFLogxK

U2 - 10.1002/jmv.20582

DO - 10.1002/jmv.20582

M3 - Article

C2 - 16555280

AN - SCOPUS:33645943739

VL - 78

SP - 608

EP - 613

JO - Journal of Medical Virology

JF - Journal of Medical Virology

SN - 0146-6615

IS - 5

ER -