title: Long-term increase in CD4+ T-cell counts during combination antiretroviral therapy for HIV-1 infection.
abstract: OBJECTIVE
  To inform guidelines concerning when to initiate combination antiretroviral therapy (ART), we investigated whether CD4(+) T-cell counts (CD4 cell counts) continue to increase over long periods of time on ART. Losses-to-follow-up and some patients discontinuing ART at higher CD4 cell counts hamper such evaluation, but novel statistical methods can help address these issues. We estimated the long-term CD4 cell count trajectory accounting for losses-to-follow-up and treatment discontinuations.
  
  
  METHODS
  The study population included 898 US patients first initiating ART in a randomized trial (AIDS Clinical Trials Group 384); 575 were subsequently prospectively followed in an observational study (AIDS Clinical Trials Group Longitudinal Linked Randomized Trials).
  
  
  METHODS
  Inverse probability of censoring weighting statistical methods were used to estimate the CD4 cell count trajectory accounting for losses-to-follow-up and ART discontinuations, overall and for pretreatment CD4 cell count categories (<or=200, 201-350, 351-500, and >500 cells/microl).
  
  
  RESULTS
  Median CD4 cell count increased from 270 cells/microl pre-ART to an estimated 556 cells/microl at 3 and 532 cells/microl at 7 years after starting ART in analyses ignoring treatment discontinuations, and to 570 and 640 cells/microl, respectively, had all patients continued ART. However, even had ART been continued, an estimated 25, 9, 3, and 2% of patients with pretreatment CD4 cell counts of 200 or less, 201-350, 351-500, and more than 500 cells/microl would have had CD4 cell counts of 350 cells/microl or less after 7 years.
  
  
  CONCLUSIONS
  If patients remain on ART, CD4 cell counts increase in most patients for at least 7 years. However, the substantial percentage of patients starting therapy at low CD4 cell counts who still had low CD4 cell counts after 7 years provides support for ART initiation at higher CD4 cell counts.
authors.affiliation: Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. jlok@hsph.harvard.edu
authors.forename: Judith J
authors.initials: JJ
authors.lastname: Lok
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Bosch
authors.forename: Constance A
authors.initials: CA
authors.lastname: Benson
authors.forename: Ann C
authors.initials: AC
authors.lastname: Collier
authors.forename: Gregory K
authors.initials: GK
authors.lastname: Robbins
authors.forename: Robert W
authors.initials: RW
authors.lastname: Shafer
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D017410:Practice Guidelines as Topic; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D019562:Viral Load
references.citation: Open AIDS J. 2008;2:3-9
references.pmid: 18923700
references.citation: Clin Infect Dis. 2007 Feb 1;44(3):441-6
references.pmid: 17205456
references.citation: N Engl J Med. 2003 Dec 11;349(24):2293-303
references.pmid: 14668455
references.citation: BMJ. 2007 Jan 13;334(7584):76-8
references.pmid: 17218713
references.citation: Clin Infect Dis. 2007 Mar 1;44(5):749-54
references.pmid: 17278071
references.citation: Clin Infect Dis. 2009 Mar 15;48(6):787-94
references.pmid: 19193107
references.citation: AIDS. 2010 Jan 2;24(1):123-37
references.pmid: 19770621
references.citation: Curr Opin HIV AIDS. 2006 Jan;1(1):43-9
references.pmid: 19372783
references.citation: AIDS. 2008 Oct 18;22(16):2143-53
references.pmid: 18832878
references.citation: N Engl J Med. 2003 Dec 11;349(24):2304-15
references.pmid: 14668456
references.citation: Lancet. 2007 Aug 4;370(9585):407-13
references.pmid: 17659333
references.citation: JAMA. 2008 Aug 6;300(5):555-70
references.pmid: 18677028
references.citation: N Engl J Med. 2009 Apr 30;360(18):1815-26
references.pmid: 19339714
references.citation: Clin Infect Dis. 2008 Dec 15;47(12):1580-6
references.pmid: 18990069
references.citation: Lancet. 2006 Dec 16;368(9553):2125-35
references.pmid: 17174704
references.citation: Curr Opin Infect Dis. 2009 Apr;22(2):191-7
references.pmid: 19283914
references.citation: J Acquir Immune Defic Syndr. 2007 Jun 1;45(2):183-92
references.pmid: 17414934
references.citation: Clin Infect Dis. 2005 Aug 1;41(3):361-72
references.pmid: 16007534
references.citation: J Acquir Immune Defic Syndr. 2006 Aug 1;42(4):426-34
references.pmid: 16810109
references.citation: J Infect Dis. 2008 Aug 15;198(4):456-64
references.pmid: 18598193
references.citation: J Infect Dis. 2008 Apr 15;197(8):1133-44
references.pmid: 18476292
references.citation: Lancet. 2006 Jul 22;368(9532):287-98
references.pmid: 16860698
references.citation: Clin Infect Dis. 2009 Feb 1;48(3):350-61
references.pmid: 19123865
references.citation: AIDS. 2008 Sep;22 Suppl 3:S13-8
references.pmid: 18845917
references.citation: Am J Epidemiol. 2008 Sep 15;168(6):656-64
references.pmid: 18682488
references.citation: AIDS. 2004 Sep 24;18(14):1953-6
references.pmid: 15353982
references.citation: N Engl J Med. 2006 Nov 30;355(22):2283-96
references.pmid: 17135583
references.citation: Basic Clin Pharmacol Toxicol. 2006 Mar;98(3):237-42
references.pmid: 16611197
references.citation: AIDS. 2003 Sep 26;17(14):2015-23
references.pmid: 14502004
references.citation: Lancet. 2009 Apr 18;373(9672):1314-6
references.pmid: 19361856
references.citation: J Infect Dis. 2006 Sep 1;194(5):612-22
references.pmid: 16897660
references.citation: J Acquir Immune Defic Syndr. 2004 Jun 1;36(2):702-13
references.pmid: 15167289
references.citation: AIDS. 2008 Apr 23;22(7):841-8
references.pmid: 18427202
references.citation: J Virol. 2003 Nov;77(21):11708-17
references.pmid: 14557656
references.citation: HIV Clin Trials. 2008 Jul-Aug;9(4):269-82
references.pmid: 18753121
references.citation: Lancet. 2009 Apr 18;373(9672):1352-63
references.pmid: 19361855
references.citation: J Infect Dis. 2008 Apr 15;197(8):1084-6
references.pmid: 18462158
references.citation: AIDS. 2003 Sep 5;17(13):1907-15
references.pmid: 12960823
references.citation: Curr Opin HIV AIDS. 2009 May;4(3):165-6
references.pmid: 19532044