title: Monophylogenetic HIV-1C epidemic in Ethiopia is dominated by CCR5-tropic viruses-an analysis of a prospective country-wide cohort.
abstract: CCR5 coreceptor using HIV-1 subtype C (HIV-1C) has been reported to dominate the Ethiopian epidemic. However, almost all data have been obtained from two large cities in the central and north-west regions and recent data is lacking.
  
  
  
  Plasma were obtained from 420 treatment-naïve patients recruited 2009-2011 to a large country-wide Ethiopian cohort. The V3 region was sequenced and the co-receptor tropism was predicted by the clinical and clonal models of the geno2pheno tool at different false positive rates (fpr) and for subtype. In an intention to treat analysis the impact of baseline tropism on outcome of antiretroviral therapy was evaluated.
  
  
  
  V3 loop sequencing was successful in 352 (84%) patients. HIV-1C was found in 350 (99.4%) and HIV-1A in two (0.6%) patients. When comparing the geno2pheno fpr10% clonal and clinical models, 24.4% predictions were discordant. X4-virus was predicted in 17.0 and 19.0%, respectively, but the predictions were concordant in only 6%. At fpr5%, concordant X4-virus predictions were obtained in 3.1%. The proportion of X4-tropic virus (clonal fpr10%) increased from 5.6 to 17.3% (p < 0.001) when 387 Ethiopian V3 loop sequences dated from 1984 to 2003 were compared with ours. In an intention to treat analysis, 67.9% reached treatment success at month 6 and only 50% at month 12. Only age and not tropism predicted therapy outcome and no difference was found in CD4+ cell gain between R5-tropic and X4-tropic infected patients. At viral failure, R5 to X4 switch was rare while X4 to R5 switch occurred more frequently (month 6: p = 0.006; month 12: p = 0.078).
  
  
  
  The HIV-1C epidemic is monophylogenetic in all regions of Ethiopia and R5-tropic virus dominates, even in patients with advanced immunodeficiency, although the proportion of X4-tropic virus seems to have increased over the last two decades. Geno2pheno clinical and clonal prediction models show a large discrepancy at fpr10%, but not at fpr5%. Hence further studies are needed to assess the utility of genotypic tropism testing in HIV-1C. In ITT analysis only age and not tropism influenced the outcome.
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Alfred Nobels Alle 8, F68, Huddinge, Stockholm, 14186, Sweden. amare.worku.kalu@ki.se.|Department of Microbiology, Immunology and Parasitology, Addis Ababa University, Addis Ababa, Ethiopia. amare.worku.kalu@ki.se.
authors.forename: Amare Worku
authors.initials: AW
authors.lastname: Kalu
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Alfred Nobels Alle 8, F68, Huddinge, Stockholm, 14186, Sweden.|Department of Microbiology, Immunology and Parasitology, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Nigus Fikrie
authors.initials: NF
authors.lastname: Telele
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Solomon
authors.initials: S
authors.lastname: Gebreselasie
authors.affiliation: Department of internal Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fekade
authors.affiliation: Public Health Agency of Sweden, Solna, Sweden.|Department of Science and Technology, Örebro University, Örebro, Sweden.
authors.forename: Samir
authors.initials: S
authors.lastname: Abdurahman
authors.affiliation: Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Marrone
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Alfred Nobels Alle 8, F68, Huddinge, Stockholm, 14186, Sweden.|Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Sönnerborg
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000821:virology; D015331:Cohort Studies; D058872:Epidemics; D005002:Ethiopia / Q000453:epidemiology; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification / Q000472:pathogenicity / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D019562:Viral Load; D056189:Viral Tropism / Q000235:genetics
chemical_list: C584933:CCR5 protein, human; D019713:Receptors, CCR5
keywords: Antiretroviral treatment; Co-receptor; Country-wide; Ethiopia; Geno2pheno; Subtype C