title: Genetic characterization of multiple hepatitis C virus infections following acute infection in HIV-infected men who have sex with men.
abstract: OBJECTIVE
  High rates of hepatitis C virus (HCV) reinfections among HIV-infected men who have sex with men (MSM) following clearance of a primary infection suggest absence of protective immunity. Here, we investigated the incidence of HCV super and reinfections in 85 HIV-infected MSM with incident HCV infection.
  
  
  METHODS
  Serial sequencing of a fragment of NS5B and the HCV envelope was used to longitudinally characterize the virus. If the primary genotype was still present at the most recent viremic time point, as indicated by the NS5B sequence analysis, serial envelope 2/hypervariable region 1 (E2/HRV1) sequence analysis was performed to distinguish a new infection with the same genotype (clade switch) from intrahost evolution. Incidence rate and cumulative incidence of secondary infections were estimated, and the effect of the primary genotype (1a versus non1) on the risk of acquiring a second infection with the same genotype was determined using Cox proportional-hazards analysis.
  
  
  RESULTS
  Among 85 patients with a median follow-up of 4.8 years, incidence rate of secondary infections was 5.39 cases/100 person-years (95% confidence interval 3.34-8.26). Cumulative incidence of genotype switches was markedly higher than the cumulative incidence of clade switches (26.7 versus 4.8% at 5 years, respectively). In patients with HCV-1a as primary infection, the risk for acquiring another HCV-1a infection was reduced compared to those with a primary non-HCV-1a subsequently acquiring HCV-1a (hazard ratio 0.25, 95% confidence interval 0.07-0.93).
  
  
  CONCLUSIONS
  Risk of acquiring a secondary infection with the primary genotype was strikingly reduced compared with the risk of acquiring a secondary infection with a different genotype.
authors.affiliation: aAcademic Medical Center, Department of Medical Microbiology, Section of Clinical Virology bPublic Health Service of Amsterdam, Department of Research, Cluster of Infectious Diseases cDepartment of Internal Medicine, Division of Infectious Diseases Amsterdam, Amsterdam, The Netherlands.
authors.forename: Xiomara V
authors.initials: XV
authors.lastname: Thomas
authors.forename: Bart P X
authors.initials: BP
authors.lastname: Grady
authors.forename: Jan T M
authors.initials: JT
authors.lastname: Van Der Meer
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Ho
authors.forename: Joost W
authors.initials: JW
authors.lastname: Vanhommerig
authors.forename: Sjoerd P
authors.initials: SP
authors.lastname: Rebers
authors.forename: Menno D
authors.initials: MD
authors.lastname: De Jong
authors.forename: Marc
authors.initials: M
authors.lastname: Van Der Valk
authors.forename: Maria
authors.initials: M
authors.lastname: Prins
authors.forename: Richard
authors.initials: R
authors.lastname: Molenkamp
authors.forename: Janke
authors.initials: J
authors.lastname: Schinkel
mesh_terms: D000328:Adult; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000453:epidemiology / Q000635:transmission* / Q000821:virology*; D018451:Homosexuality, Male; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D011446:Prospective Studies; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase
chemical_list: D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C091015:glycoprotein E2, Hepatitis C virus; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase