Trends and predictors of transmitted drug resistance (TDR) and clusters with TDR in a local Belgian HIV-1 epidemic

PLoS One. 2014 Jul 8;9(7):e101738. doi: 10.1371/journal.pone.0101738. eCollection 2014.

Abstract

We aimed to study epidemic trends and predictors for transmitted drug resistance (TDR) in our region, its clinical impact and its association with transmission clusters. We included 778 patients from the AIDS Reference Center in Leuven (Belgium) diagnosed from 1998 to 2012. Resistance testing was performed using population-based sequencing and TDR was estimated using the WHO-2009 surveillance list. Phylogenetic analysis was performed using maximum likelihood and Bayesian techniques. The cohort was predominantly Belgian (58.4%), men who have sex with men (MSM) (42.8%), and chronically infected (86.5%). The overall TDR prevalence was 9.6% (95% confidence interval (CI): 7.7-11.9), 6.5% (CI: 5.0-8.5) for nucleoside reverse transcriptase inhibitors (NRTI), 2.2% (CI: 1.4-3.5) for non-NRTI (NNRTI), and 2.2% (CI: 1.4-3.5) for protease inhibitors. A significant parabolic trend of NNRTI-TDR was found (p = 0.019). Factors significantly associated with TDR in univariate analysis were male gender, Belgian origin, MSM, recent infection, transmission clusters and subtype B, while multivariate and Bayesian network analysis singled out subtype B as the most predictive factor of TDR. Subtype B was related with transmission clusters with TDR that included 42.6% of the TDR patients. Thanks to resistance testing, 83% of the patients with TDR who started therapy had undetectable viral load whereas half of the patients would likely have received a suboptimal therapy without this test. In conclusion, TDR remained stable and a NNRTI up-and-down trend was observed. While the presence of clusters with TDR is worrying, we could not identify an independent, non-sequence based predictor for TDR or transmission clusters with TDR that could help with guidelines or public health measures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • Belgium / epidemiology
  • Cluster Analysis
  • Drug Resistance, Viral / genetics*
  • Female
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / epidemiology*
  • HIV Infections / transmission
  • HIV Infections / virology*
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Pregnancy
  • Prevalence
  • Public Health Surveillance
  • Retrospective Studies
  • Risk Factors
  • Young Adult

Substances

  • Anti-HIV Agents

Grants and funding

This work was supported in part by the AIDS Reference Laboratory of Leuven that receives support from the Belgian Ministry of Social Affairs through a fund within the Health Insurance System; by the Fonds voor Wetenschappelijk Onderzoek – Flanders (FWO) grant G069214N; and by the European Community's Seventh Framework Programme (FP7/2007-2013) under the project “Collaborative HIV and Anti-HIV Drug Resistance Network (CHAIN)” grant agreement N° 223131; by the University of Leuven (Program Financing no. PF/10/018); by the Doctoral Research Training Program “Francisco Jose de Caldas” by the Departamento Administrativo de Ciencia, Tecnología e Innovación, COLCIENCIAS, Republic of Colombia and by ERACOL, a scholarship for academic exchange in medicine and the health sciences between Europe and Latin America to A.C.P.P. The computational resources and services used in this work were provided by the Hercules Foundation and the Flemish Government – department EWI-FWO Krediet aan Navorsers (Theys, KAN2012 1.5.249.12). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.