title: Estimated average annual rate of change of CD4(+) T-cell counts in patients on combination antiretroviral therapy.
abstract: BACKGROUND
  Patients receiving combination antiretroviral therapy (cART) might continue treatment with a virologically failing regimen. We sought to identify annual change in CD4(+) T-cell count according to levels of viraemia in patients on cART.
  
  
  METHODS
  A total of 111,371 CD4(+) T-cell counts and viral load measurements in 8,227 patients were analysed. Annual change in CD4(+) T-cell numbers was estimated using mixed models.
  
  
  RESULTS
  After adjustment, the estimated average annual change in CD4(+) T-cell count significantly increased when viral load was <500 copies/ml (30.4 cells/mm(3), 95% confidence interval [CI] 26.6-34.3), was stable when viral load was 500-9,999 copies/ml (3.1 cells/mm(3), 95% CI -5.3-11.5) and decreased when viral load was > or =10,000 copies/ml (-14.8 cells/mm(3), 95% CI -4.5--25.1). Patients taking a boosted protease inhibitor (PI) regimen had more positive annual CD4(+) T-cell count changes than patients taking other regimens for any given viral load strata: 30.9 cells/mm(3) (95% CI 27.7-34.1) when viral load was <500 copies/ml, 14.2 cells/mm(3) (95% CI -2.1-30.4) when viral load was 500-9,999 copies/ml and -19.9 cells/mm(3) (95% CI -36.6--3.3) when viral load was >or =10,000 copies/ml. By contrast, among patients taking a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, the CD4(+) T-cell count significantly decreased when the viral load was 500-9,999 copies/ml (-18.6 cells/mm(3), 95% CI -33.8--3.5) and decreased at a faster rate when the viral load was > or =10,000 copies/ml (-44.4 cells/mm(3), 95% CI -62.0--26.9; P=0.0012, test for interaction).
  
  
  CONCLUSIONS
  On average, CD4(+) T-cell counts did not significantly decrease until the viral load exceeded 10,000 copies/ml in patients treated with a boosted PI-containing cART regimen, but decreased in patients taking an NNRTI-based cART regimen when viral load was 500-9,999 copies/ml.
authors.affiliation: Research Department of Infection and Population Health, University College London Medical School, London, UK. a.mocroft@ucl.ac.uk
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.forename: Bruno
authors.initials: B
authors.lastname: Ledergerber
authors.forename: Colette
authors.initials: C
authors.lastname: Smith
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Bogner
authors.forename: Karine
authors.initials: K
authors.lastname: Lacombe
authors.forename: Alicje
authors.initials: A
authors.lastname: Wiercinska-Drapalo
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Ole
authors.initials: O
authors.lastname: Kirk
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology* / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors