title: The HIV RNA setpoint theory revisited.
abstract: BACKGROUND
  The evolution of plasma viral load after HIV infection has been described as reaching a setpoint, only to start rising again shortly before AIDS diagnosis. In contrast, CD4 T-cell count is considered to show a stable decrease. However, characteristics of marker evolution over time depend on the scale that is used to visualize trends. In reconsidering the setpoint theory for HIV RNA, we analyzed the evolution of CD4 T-cell count and HIV-1 RNA level from HIV seroconversion to AIDS diagnosis. Follow-up data were used from two cohort studies among homosexual men (N = 400), restricting to the period before highly active antiretroviral therapy became widely available (1984 until 1996). Individual trajectories of both markers were fitted and averaged, both from seroconversion onwards and in the four years preceding AIDS diagnosis, using a bivariate random effects model. Both markers were evaluated on a scale that is directly related to AIDS risk.
  
  
  RESULTS
  Individuals with faster AIDS progression had higher HIV RNA level six months after seroconversion. For CD4 T-cell count, this ordering was less clearly present. However, HIV RNA level and CD4 T-cell count showed qualitatively similar evolution over time after seroconversion, also when stratified by rate of progression to AIDS. In the four years preceding AIDS diagnosis, a non-significant change in HIV RNA increase was seen, whereas a significant biphasic pattern was present for CD4 T-cell decline.
  
  
  CONCLUSIONS
  HIV RNA level has more setpoint behaviour than CD4 T-cell count as far as the level shortly after seroconversion is concerned. However, with respect to the, clinically more relevant, marker evolution over time after seroconversion, a setpoint theory holds as much for CD4 T-cell count as for HIV RNA level.
authors: Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands. statistics@inter.nl.net
authors: Ronald B
authors: RB
authors: Geskus
authors: Maria
authors: M
authors: Prins
authors: Jean-Baptiste
authors: JB
authors: Hubert
authors: Frank
authors: F
authors: Miedema
authors: Ben
authors: B
authors: Berkhout
authors: Christine
authors: C
authors: Rouzioux
authors: Jean-Francois
authors: JF
authors: Delfraissy
authors: Laurence
authors: L
authors: Meyer
mesh_terms: D000328:Adult; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015331:Cohort Studies; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D006716:Homosexuality; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load
chemical_list: D015415:Biomarkers; D012367:RNA, Viral