title: The temporal increase in HIV-1 non-R5 tropism frequency among newly diagnosed patients from northern Poland is associated with clustered transmissions.
abstract: BACKGROUND
  CCR5 (R5) tropic viruses are associated with early stages of infection, whereas CXCR4 (X4) HIV-1 tropism has been associated with severe immunodeficiency. We investigated the temporal changes in the genotype-predicted tropism frequency and the phylogenetic relationships between the R5 and non-R5 clades.
  
  
  METHODS
  A cohort of 194 patients with a newly diagnosed HIV infection that was linked to their care from 2007 to 2014 was analyzed. Baseline plasma samples were used to assess the HIV-1 genotypic tropism with triplicate V3-loop sequencing. The non-R5 tropism prediction thresholds were assigned using a false positive rate (FPR) of 10 and 5.75% and associated with clinical and laboratory data. The transmission clusters were analyzed using pol sequences with a maximum likelihood and Bayesian inference.
  
  
  RESULTS
  The overall non-R5 tropism frequency for 5.75% FPR was 15.5% (n=30) and 27.8% (n=54) for 10% FPR. The frequency of the non-R5 tropism that was predicted using 5.75% FPR increased significantly from 2007 (0%) to 2014 (n=5/17, 29.4%) (p=0.004, rough slope +3.73%/year) and from 0% (2007) to 35.3% (2014, n=6/17) (p=0.071, rough slope +2.9%/year) using 10% FPR. Increase in the asymptomatic diagnoses over time was noted (p=0.05, rough slope +3.53%/year) along with a tendency to increase the lymphocyte CD4 nadir (p=0.069). Thirty-two clusters were identified, and non-R5 tropic viruses were found for 26 (30.95%) sequences contained within 14 (43.8%) clusters. Non-R5 tropism was associated with subtype D variants (p=0.0001) and the presence of CCR5 Δ32/wt genotype (p=0.052).
  
  
  CONCLUSIONS
  R5 tropism predominates among the treatment of naive individuals, but the increases in the frequency of non-R5 tropic variants may limit the clinical efficacy of the co-receptor inhibitors. The rising prevalence of non-R5 HIV-1 may indicate transmission of X4 clades.
authors: Department of Infectious, Tropical Diseases and Acquired Immune Deficiency, Pomeranian Medical University, Szczecin, Poland; mparczewski@yahoo.co.uk.
authors: Miłosz
authors: M
authors: Parczewski
authors: Department of Infectious, Tropical Diseases and Acquired Immune Deficiency, Pomeranian Medical University, Szczecin, Poland.
authors: Magdalena
authors: M
authors: Leszczyszyn-Pynka
authors: Department of Infectious, Tropical Diseases and Acquired Immune Deficiency, Pomeranian Medical University, Szczecin, Poland.
authors: Magdalena
authors: M
authors: Witak-Jędra
authors: Department of Infectious, Tropical Diseases and Acquired Immune Deficiency, Pomeranian Medical University, Szczecin, Poland.
authors: Katarzyna
authors: K
authors: Maciejewska
authors: Department of Infectious, Tropical Diseases and Acquired Immune Deficiency, Pomeranian Medical University, Szczecin, Poland.
authors: Sławomira
authors: S
authors: Myślińska
authors: Department of Infectious, Tropical Diseases and Acquired Immune Deficiency, Pomeranian Medical University, Szczecin, Poland.
authors: Anna
authors: A
authors: Urbańska
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011044:Poland; D019713:Receptors, CCR5 / Q000502:physiology*; D056189:Viral Tropism
chemical_list: C584933:CCR5 protein, human; D019713:Receptors, CCR5
keywords: Bayesian inference; V3 sequencing; clustering; temporal trends; tropism