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

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Pineda-Peña, Andrea-Clemencia
Schrooten, Yoeri
Vinken, Lore
Ferreira, Fossie
Li, Guangdi
Sequeira Trovao, Nidia
Khouri, Ricardo
Derdelinckx, Inge
De Munter, Paul
Kücherer, Claudia




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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. © 2014 Pineda-Peña et al.
Palabras clave
Adult , Article , Female , Middle Aged , Adult , Female , Humans , Middle Aged , Retrospective Studies , Risk Factors , Proteinase Inhibitor , Rna Directed Dna Polymerase Inhibitor , Anti Human Immunodeficiency Virus Agent , Aged , Antiviral Resistance , Belgium , Cohort Analysis , Disease Association , Disease Surveillance , Epidemic , Gender , Human , Virus 1 Infection , Immunodeficiency Virus Type , 1 Subtype B , Infection , Major Clinical Study , Male , Men Who Have Sex With Men , Phylogeny , Prediction , Prevalence , Sequence Analysis , Transmitted Drug Resistance , Trend Study , Virus Load , Virus Transmission , Antiviral Resistance , Cluster Analysis , Drug Effects , Genetics , Genotype , Health Survey , Hiv Infections , Microbial Sensitivity Test , Pregnancy , Retrospective Study , Risk Factor , Transmission , Virology , Anti-Hiv Agents , Belgium , Cluster Analysis , Drug Resistance , Viral , Genotype