Clinically relevant transmitted drug resistance to first line antiretroviral drugs and implications for recommendations

PLoS One. 2014 Mar 17;9(3):e90710. doi: 10.1371/journal.pone.0090710. eCollection 2014.

Abstract

Background: The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR) defined by the 2009 update of the WHO SDRM list.

Methods: We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain) between 2007-2011. Using the Stanford algorithm "Low-level resistance", "Intermediate resistance" and "High-level resistance" categories were considered as "Resistant".

Results: 70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8-7.7)], and 221 harbored TDR using the WHO list [7.9% (6.9-9.0)]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8-2.9) vs. 3.6% (2.9-4.3) by the WHO list] and PIs [0.8% (0.4-1.1) vs. 1.7% (1.2-2.2)], while it was higher for NNRTIs [4.6% (3.8-5.3) vs. 3.7% (3.0-4.7)]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02).

Conclusions: Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • HIV-1 / genetics*
  • HIV-1 / immunology
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Mutation
  • Prospective Studies
  • Viral Load
  • Young Adult

Substances

  • Anti-HIV Agents

Grants and funding

This work was supported by the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida [ISCIII-RETIC RD06/006 and RD12/0017], and through Grant n° PI12/01053. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.