Has the rate of CD4 cell count decline before initiation of antiretroviral therapy changed over the course of the Dutch HIV epidemic among MSM?

Luuk A. Gras, Ronald B Geskus, Suzanne Jurriaans, Margreet Bakker, Ard van Sighem, Daniela Bezemer, Christophe Fraser, Jan M. Prins, Ben Berkhout, ATHENA National Observational Cohort, Selwyn Lowe, Astrid Oude Lashof, Frank de Wolf

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numbere64437
JournalPLOS ONE
Volume8
Issue number5
DOIs
Publication statusPublished - 2013

Keywords

  • Adult
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • HIV Infections
  • Homosexuality, Male
  • Humans
  • Male
  • Netherlands
  • Journal Article
  • Research Support, Non-U.S. Gov't

Cite this

Gras, L. A., Geskus, R. B., Jurriaans, S., Bakker, M., van Sighem, A., Bezemer, D., Fraser, C., Prins, J. M., Berkhout, B., ATHENA National Observational Cohort, Lowe, S., Oude Lashof, A., & de Wolf, F. (2013). Has the rate of CD4 cell count decline before initiation of antiretroviral therapy changed over the course of the Dutch HIV epidemic among MSM? PLOS ONE, 8(5), [e64437]. https://doi.org/10.1371/journal.pone.0064437