title: Rising HIV-1 viral load set point at a population level coincides with a fading impact of host genetic factors on HIV-1 control.
abstract: OBJECTIVE
  Heterozygosity for a 32 base pair deletion in the CCR5 gene (CCR5wt/Δ32) and the minor alleles of a single-nucleotide polymorphism in the HCP5 gene (rs2395029) and in the HLA-C gene region (-35HLA-C; rs9264942) has been associated with a lower viral load set point. Recent studies have shown that over calendar time, viral load set point has significantly increased at a population level. Here we studied whether this increase coincides with a fading impact of above-mentioned host genetic markers on HIV-1 control.
  
  
  METHODS
  We compared the association between viral load set point and HCP5 rs2395029, -35HLA-C rs9264942, and the CCR5wt/Δ32 genotype in HIV-1-infected individuals in the Netherlands who had seroconverted between 1982 and 2002 (pre-2003 seroconverters, n = 459) or between 2003 and 2009 (post-2003 seroconverters, n = 231).
  
  
  RESULTS
  Viral load set point in post-2003 seroconverters was significantly higher than in pre-2003 seroconverters (P = 4.5 × 10(-5)). The minor alleles for HCP5 rs2395029, -35HLA-C rs9264942 and CCR5wt/Δ32 had a similar prevalence in both groups and were all individually associated with a significantly lower viral load set point in pre-2003 seroconverters. In post-2003 seroconverters, this association was no longer observed for HCP5 rs2395029 and CCR5wt/Δ32. The association between viral load set point and HCP5 rs2395029 had significantly changed over time, whereas the change in impact of the CCR5wt/Δ32 genotype over calendar time was not independent from the other markers under study.
  
  
  CONCLUSIONS
  The increased viral load set point at a population level coincides with a lost impact of certain host genetic factors on HIV-1 control.
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infectious Diseases and Immunity Amsterdam at the Academic Medical Center of the University of Amsterdam, The Netherlands.
authors.forename: Daniëlle
authors.initials: D
authors.lastname: van Manen
authors.forename: Luuk
authors.initials: L
authors.lastname: Gras
authors.forename: Brigitte D
authors.initials: BD
authors.lastname: Boeser-Nunnink
authors.forename: Ard I
authors.initials: AI
authors.lastname: van Sighem
authors.forename: Irma
authors.initials: I
authors.lastname: Maurer
authors.forename: Marga M
authors.initials: MM
authors.lastname: Mangas Ruiz
authors.forename: Agnes M
authors.initials: AM
authors.lastname: Harskamp
authors.forename: Radjin
authors.initials: R
authors.lastname: Steingrover
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: Angélique B
authors.initials: AB
authors.lastname: van 't Wout
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006679:HIV Seropositivity / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000276:immunology; D008297:Male; D009426:Netherlands; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D019713:Receptors, CCR5 / Q000235:genetics* / Q000276:immunology; D013997:Time Factors; D019562:Viral Load / Q000235:genetics / Q000276:immunology / Q000639:trends*
chemical_list: C080521:HCP5 long noncoding RNA, human; D015236:HLA-C Antigens; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D019713:Receptors, CCR5