Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

Introduction: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 A... Mehr ...

Verfasser: Gras, L.A. (Luuk)
Geskus, R.B. (Ronald)
Jurriaans, S. (Suzanne)
Bakker-Verweij, M. (Margreet)
Sighem, A.I. (Ard) van
Bezemer, D.O. (Daniela)
Fraser, C. (Christophe)
Prins, J.M. (Jan)
Berkhout, B. (Ben)
Wolf, F. (Frank) de
Dokumenttyp: Artikel
Erscheinungsdatum: 2013
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-27453109
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : http://repub.eur.nl/pub/67937

Introduction: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).Conclusion: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.