title: Has the rate of CD4 cell count decline before initiation of antiretroviral therapy changed over the course of the Dutch HIV epidemic among MSM?
abstract: BACKGROUND
  Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.
  
  
  METHODS
  Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART, <100 CD4 cells/mm³, or AIDS) among therapy-naïve MSM HIV-1 seroconverters in the Netherlands. These models make different assumptions about the censoring process.
  
  
  RESULTS
  All 3 models estimated lower median CD4 cell counts 9 months after seroconversion in later calendar years (623, 582, and 541 cells/mm³ for 1984-1995 [n = 111], 1996-2002 [n = 139], and 2003-2007 seroconverters [n = 356], respectively, shared-parameter model). Only the 2 joint-models found a trend for a steeper decline of CD4 cell counts with seroconversion in later calendar years (overall p-values 0.002 and 0.06 for the pattern-mixture and the shared-parameter model, respectively). In the shared-parameter model the median decline from 9 to 48 months was 276 cellsmm³ for 1984-1995 seroconverters and 308 cells/mm³ for 2003-2007 seroconverters (difference in slope, p = 0.045).
  
  
  CONCLUSIONS
  Mixed-effects models underestimate the CD4 cell decline prior to starting ART. Joint-models suggest that CD4 cell count declines more rapidly in patients infected between 2003 and 2007 compared to patients infected before 1996.
authors.affiliation: Stichting HIV Monitoring, Amsterdam, The Netherlands. l.a.gras@amc.uva.nl
authors.forename: Luuk
authors.initials: L
authors.lastname: Gras
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Geskus
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jurriaans
authors.forename: Margreet
authors.initials: M
authors.lastname: Bakker
authors.forename: Ard
authors.initials: A
authors.lastname: van Sighem
authors.forename: Daniela
authors.initials: D
authors.lastname: Bezemer
authors.forename: Christophe
authors.initials: C
authors.lastname: Fraser
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000276:immunology*; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D009426:Netherlands / Q000453:epidemiology