title: Quantitative Assessment of Intra-Patient Variation in CD4+ T Cell Counts in Stable, Virologically-Suppressed, HIV-Infected Subjects.
abstract: OBJECTIVE
  Counts of absolute CD4+ T lymphocytes (CD4+ T cells) are known to be highly variable in untreated HIV-infected individuals, but there are no data in virologically-suppressed individuals. We investigated CD4+ T cell variability in stable, virologically-suppressed, HIV-1 infected adults on combination antiretroviral therapy (cART).
  
  
  METHODS
  From a large hospital database we selected patients with stable virological suppression on cART for >3 years with >10 CD4+ T cell measurements performed over a further >2 years; and a control group of 95 patients not on cART.
  
  
  RESULTS
  We identified 161 HIV-infected patients on cART without active HCV or HBV infection, with stable virological suppression for a median of 6.4 years. Over the study period 88 patients had reached a plateau in their absolute CD4+ T cell counts, while 65 patients had increasing and 8 patients had decreasing absolute CD4+ T cell counts. In patients with plateaued CD4+ T cell counts, variability in absolute CD4+ T cell counts was greater than in percent CD4+ T cells (median coefficient of variation (CV) 16.6% [IQR 13.8-20.1%] and CV 9.6% [IQR 7.4-13.0%], respectively). Patients with increasing CD4+ T cell counts had greater variability in absolute CD4+ T cell counts than those with plateaued CD4 T cell counts (CV 19.5% [IQR 16.1-23.8%], p<0.001) while there was no difference in percent CD4+ T cell variability between the two groups. As previously reported, untreated patients had CVs significantly higher than patients on cART (CVs of 21.1% [IQR 17.2-32.0%], p<0.001 and 15.2% (IQR 10.7-20.0%), p<0.001, respectively). Age or sex did not affect the degree of CD4+ variation.
  
  
  CONCLUSIONS
  Adults with stable, virologically-suppressed HIV infection continue to have significant variations in individual absolute CD4+ T cell and percent CD4+ T cell counts; this variation can be of clinical relevance especially around CD4+ thresholds. However, the variation seen in individuals on cART is substantially less than in untreated subjects.
authors.affiliation: Department of Infectious Diseases, The Alfred hospital, Melbourne, Australia.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Gordon
authors.affiliation: Department of Infectious Diseases, The Alfred hospital, Melbourne, Australia; Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Cheng
authors.affiliation: Department of Infectious Diseases, The Alfred hospital, Melbourne, Australia; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia.
authors.forename: Paul U
authors.initials: PU
authors.lastname: Cameron
authors.affiliation: Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Bailey
authors.affiliation: Department of Infectious Diseases, The Alfred hospital, Melbourne, Australia; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Crowe
authors.affiliation: Department of Infectious Diseases, The Alfred hospital, Melbourne, Australia; Department of Epidemiology and Preventative Medicine, Monash University, Melbourne, Australia; Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia; Department of Medicine, Monash University Central Clinical School, Melbourne, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Mills
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome