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

Andrea Clemencia Pineda-Peña, Yoeri Schrooten, Lore Vinken, Fossie Ferreira, Guangdi Li, Nídia Sequeira Trovão, Ricardo Khouri, Inge Derdelinckx, Paul De Munter, Claudia Kuc̈herer, Leondios G. Kostrikis, Claus Nielsen, Kirsi Littsola, Annemarie Wensing, Maja Stanojevic, Roger Paredes, Claudia Balotta, Jan Albert, Charles Boucher, Arley Gomez-LopezEric Van Wijngaerden, Marc Van Ranst, Jurgen Vercauteren, Anne Mieke Vandamme, Kristel Van Laethem

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30 Citations (Scopus)

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.

Original languageEnglish
Article numbere101738
JournalPlosOne
Volume9
Issue number7
DOIs
Publication statusPublished - 8 Jul 2014

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