A significant reduction in the frequency of HIV-1 drug resistance in Québec from 2001 to 2011 is associated with a decrease in the monitored viral load.

Hugues Charest,Isabelle Hardy,Mark A Wainberg,Daniela Moisi,Ernest Lo,Cécile Tremblay,Florence Doualla-Bell,Bluma Brenner,Donald G Murphy,Régis Cantin,Jean-Guy Baril,Michel Roger,Linda Lemieux,Nicolas Sluis-Cremer

doi:10.1371/journal.pone.0109420

Abstract

BackgroundHIV drug resistance represents a major threat for effective treatment. We assessed the trends in the frequency of drug resistance mutations and the monitored viral load (VL) in treatment-naïve (TN) and treatment-experienced (TE) individuals infected with HIV-1 in Québec, Canada, between 2001 and 2011.Methods and FindingsResistance data were obtained from 4,105 and 5,086 genotypic tests performed on TN and TE patients, respectively. Concomitantly, 274,161 VL tests were carried out in the Province. Changes over time in drug resistance frequency and in different categories of VL were assessed using univariate logistic regression. Multiple logistic regression was used to evaluate associations between the rates of certain mutations and antiretroviral prescriptions. From 2001 to 2011, the proportion of undetectable VL test results continually increased, from 42.1% to 75.9%, while a significant decrease in the frequency of resistance mutations associated with protease inhibitors [PI (from 54% to 16%)], nucleoside [NRTI (from 78% to 37%) and non-nucleoside reverse transcriptase inhibitors [NNRTI (from 44% to 31%)] was observed in TE patients. In TN individuals, the overall frequency of transmitted drug resistance was 13.1%. A multiple logistic regression analysis indicated that the introduction of co-formulated emtricitabine/tenofovir or emtricitabine/tenofovir/efavirenz was positively associated with the decrease of the frequency of the M184I/V mutations observed overtime (p = 0.0004).ConclusionsWe observed a significant decrease in the frequency of drug resistance mutations in TE patients, concomitant with a decrease in the proportion of patients with detectable viremia. These findings may be related to both the increased potencies and adherence to therapy associated with newer antiretroviral regimens. Nevertheless, our data demonstrate that broad use of antiretrovirals does not increase the level of circulating drug resistant variants.

Highlights

We observed a significant decrease in the frequency of drug resistance mutations in TE patients, concomitant with a decrease in the proportion of patients with detectable viremia
In view of the recent findings of the efficacy of antiretroviral therapy (ART), for the health benefit of individuals [1,2] and to prevent HIV transmission [2], programs to expand the use of ART have been implemented in several countries
Viral load testing The number of viral load (VL) tests performed yearly in the province increased from 21,600 in 2001 to over 28,400 in 2011

Summary

Introduction

In view of the recent findings of the efficacy of antiretroviral therapy (ART), for the health benefit of individuals [1,2] and to prevent HIV transmission [2], programs to expand the use of ART have been implemented in several countries. Trends in monitored viral load and frequency of HIV-drug resistance are good indicators of the effectiveness of clinical and public health interventions throughout the cascade of care, from diagnosis to viral suppression [3,4,5,6]. Our study aimed to analyze the frequency and putative determinants of HIV-1 drug resistance in patients in the province of Quebec from 2001 to 2011, as monitored through the use of two surveillance program databases. HIV drug resistance represents a major threat for effective treatment. We assessed the trends in the frequency of drug resistance mutations and the monitored viral load (VL) in treatment-naıve (TN) and treatment-experienced (TE) individuals infected with HIV-1 in Quebec, Canada, between 2001 and 2011

Methods

Results

Discussion

Conclusion