title: Trends and predictors of transmitted drug resistance (TDR) and clusters with TDR in a local Belgian HIV-1 epidemic.
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.
authors.affiliation: Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; Clinical and Molecular Infectious Diseases Group, Faculty of Sciences and Mathematics, Universidad del Rosario, Bogotá, Colombia.
authors.forename: Andrea-Clemencia
authors.initials: AC
authors.lastname: Pineda-Peña
authors.affiliation: Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; AIDS Reference Laboratory, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Yoeri
authors.initials: Y
authors.lastname: Schrooten
authors.affiliation: Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Lore
authors.initials: L
authors.lastname: Vinken
authors.affiliation: Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Fossie
authors.initials: F
authors.lastname: Ferreira
authors.affiliation: Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Guangdi
authors.initials: G
authors.lastname: Li
authors.affiliation: Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Nídia Sequeira
authors.initials: NS
authors.lastname: Trovão
authors.affiliation: Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Khouri
authors.affiliation: Clinical Infectious and Inflammatory Disorders, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Derdelinckx
authors.affiliation: Clinical Infectious and Inflammatory Disorders, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: De Munter
authors.affiliation: Robert Koch-Institut, Berlin, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Kücherer
authors.affiliation: University of Cyprus, Nicosia, Cyprus.
authors.forename: Leondios G
authors.initials: LG
authors.lastname: Kostrikis
authors.affiliation: Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Nielsen
authors.affiliation: National Institute of health and welfare, Helsinki, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Littsola
authors.affiliation: Department of Virology, University Medical Center Utrecht, The Netherlands.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Wensing
authors.affiliation: University of Belgrade, Faculty of Medicine, Belgrade, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Stanojevic
authors.affiliation: IrsiCaixa Foundation, Badalona, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Paredes
authors.affiliation: Luigi Sacco University Hospital, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Balotta
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Albert
authors.affiliation: Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Charles
authors.initials: C
authors.lastname: Boucher
authors.affiliation: Clinical and Molecular Infectious Diseases Group, Faculty of Sciences and Mathematics, Universidad del Rosario, Bogotá, Colombia.
authors.forename: Arley
authors.initials: A
authors.lastname: Gomez-Lopez
authors.affiliation: Clinical Infectious and Inflammatory Disorders, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Wijngaerden
authors.affiliation: Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; AIDS Reference Laboratory, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Van Ranst
authors.affiliation: Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Vercauteren
authors.affiliation: Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; Centro de Malária e outras Doenças Tropicais and Unidade de Microbiologia, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: Anne-Mieke
authors.initials: AM
authors.lastname: Vandamme
authors.affiliation: Clinical and Epidemiological Virology, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; AIDS Reference Laboratory, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Kristel
authors.initials: K
authors.lastname: Van Laethem
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D001530:Belgium / Q000453:epidemiology; D016000:Cluster Analysis; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011247:Pregnancy; D015995:Prevalence; D062486:Public Health Surveillance; D012189:Retrospective Studies; D012307:Risk Factors; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents