title: Older HIV-infected patients on antiretroviral therapy have B-cell expansion and attenuated CD4 cell increases with immune activation reduction.
abstract: BACKGROUND
  The contribution of immune activation to accelerated HIV-disease progression in older individuals has not been delineated.
  
  
  METHODS
  Prospective multicenter cohort of older (≥45 years) and younger (18-30 years) HIV-infected adults initiating 192 weeks of antiretroviral therapy (ART). Longitudinal models of CD4 cell restoration examined associations with age-group, thymic volume, immune activation, and viral load.
  
  
  RESULTS
  Forty-five older and 45 younger adults (median age 50 and 26 years, respectively) were studied. Older patients had fewer naive CD4 cells (P<0.001) and higher HLA-DR/CD38 expression on CD4 (P=0.05) and CD8 cells (P=0.07) than younger patients at any time on ART. The rate of naive and total CD4 cell increase was similar between age groups, but older patients had a faster mean rate of B-cell increase (by +0.7 cells/week; P=0.01), to higher counts than healthy controls after 192 weeks (P=0.003). Naive CD4 increases from baseline were associated with immune activation reductions (as declines from baseline of %CD8 cells expressing HLA-DR/CD38; P<0.0001), but these increases were attenuated in older patients, or in those with small thymuses. A 15% reduction in activation was associated with naive gains of 29.9 and 6.2 cells/μl in younger, versus older patients, or with gains of 25.7, 23.4, and 2.1 cells/μl in patients with the largest, intermediate, and smallest thymuses, respectively (P<0.01 for interactions between activation reduction and age-group or thymic volume).
  
  
  CONCLUSIONS
  Older patients had significant B-cell expansion, higher levels of immune activation markers, and significantly attenuated naive CD4 cell gains associated with activation reduction.
authors.affiliation: MetroHealth Medical Center, Cleveland, OH, USA. rkalayjian@metrohealth.org
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kalayjian
authors.forename: John
authors.initials: J
authors.lastname: Spritzler
authors.forename: Roy M
authors.initials: RM
authors.lastname: Matining
authors.forename: Susan A
authors.initials: SA
authors.lastname: Fiscus
authors.forename: Barry H
authors.initials: BH
authors.lastname: Gross
authors.forename: Isaac R
authors.initials: IR
authors.lastname: Francis
authors.forename: Richard B
authors.initials: RB
authors.lastname: Pollard
authors.forename: Michael M
authors.initials: MM
authors.lastname: Lederman
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000375:Aging / Q000276:immunology; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D006684:HLA-DR Antigens; D047889:Receptors, Tumor Necrosis Factor, Type II; D051997:ADP-ribosyl Cyclase 1
references.citation: J Acquir Immune Defic Syndr. 2011 Dec 1;58(4):363-70
references.pmid: 21792066
references.citation: PLoS One. 2012;7(8):e43803
references.pmid: 22970105
references.citation: J Clin Invest. 1999 Oct;104(8):1031-9
references.pmid: 10525041
references.citation: J Infect Dis. 1998 Aug;178(2):360-7
references.pmid: 9697715
references.citation: Clin Infect Dis. 2011 Dec;53(11):1120-6
references.pmid: 21998278
references.citation: Clin Infect Dis. 2003 Aug 15;37(4):551-8
references.pmid: 12905140
references.citation: Nat Genet. 2011 Jun 26;43(8):806-10
references.pmid: 21706004
references.citation: AIDS Res Ther. 2010 Dec 15;7:45
references.pmid: 21159161
references.citation: Trends Immunol. 2002 Dec;23(12):580-5
references.pmid: 12464569
references.citation: J Acquir Immune Defic Syndr. 2007 Mar 1;44(3):268-77
references.pmid: 17146370
references.citation: AIDS. 2001 Sep 28;15(14):1801-9
references.pmid: 11579242
references.citation: J Clin Invest. 1998 Jun 1;101(11):2301-8
references.pmid: 9616201
references.citation: J Infect Dis. 2002 Jun 1;185(11):1578-85
references.pmid: 12023763
references.citation: PLoS Med. 2008 Oct 21;5(10):e203
references.pmid: 18942885
references.citation: N Engl J Med. 2009 Apr 30;360(18):1815-26
references.pmid: 19339714
references.citation: J Acquir Immune Defic Syndr. 2006 Aug 1;42(4):426-34
references.pmid: 16810109
references.citation: J Infect Dis. 2004 Jul 1;190(1):148-55
references.pmid: 15195254
references.citation: J Infect Dis. 2010 Jun 15;201(12):1796-805
references.pmid: 20446847
references.citation: PLoS One. 2011 Jan 26;6(1):e16459
references.pmid: 21298072
references.citation: AIDS. 2000 Jul 7;14(10):1309-16
references.pmid: 10930144
references.citation: J Immunol. 2002 Sep 15;169(6):3400-6
references.pmid: 12218162
references.citation: Clin Infect Dis. 2009 Feb 1;48(3):350-61
references.pmid: 19123865
references.citation: AIDS. 1996 Jul;10(8):F17-22
references.pmid: 8828735
references.citation: J Infect Dis. 2000 Jan;181(1):141-7
references.pmid: 10608760
references.citation: AIDS. 2002 Jan 4;16(1):21-9
references.pmid: 11741159
references.citation: AIDS Res Hum Retroviruses. 2010 Jun;26(6):635-43
references.pmid: 20560793
references.citation: J Clin Invest. 1995 May;95(5):2061-6
references.pmid: 7738173
references.citation: AIDS. 2004 Jan 1;18 Suppl 1:S19-25
references.pmid: 15075494
references.citation: J Infect Dis. 2003 Jun 15;187(12):1924-33
references.pmid: 12792869
references.citation: J Infect Dis. 2005 Nov 1;192(9):1577-87
references.pmid: 16206072
references.citation: Blood. 2009 Jan 22;113(4):769-74
references.pmid: 18583570
references.citation: Lancet. 2002 Jul 13;360(9327):119-29
references.pmid: 12126821
references.citation: Lancet. 2000 Apr 1;355(9210):1131-7
references.pmid: 10791375
references.citation: JAMA. 2006 Aug 16;296(7):782-93
references.pmid: 16905784
references.citation: AIDS. 2011 Jan 28;25(3):303-14
references.pmid: 21192231
references.citation: Annu Rev Med. 2011;62:141-55
references.pmid: 21090961
references.citation: AIDS. 2011 Nov 13;25(17):2123-31
references.pmid: 21881481
references.citation: Clin Immunol. 1999 Nov;93(2):114-23
references.pmid: 10527687
references.citation: J Infect Dis. 2003 May 15;187(10):1534-43
references.pmid: 12721933
references.citation: Ann Intern Med. 2000 Jul 4;133(1):21-30
references.pmid: 10877736
references.citation: AIDS. 2012 Apr 24;26(7):843-53
references.pmid: 22313961
references.citation: AIDS. 2004 Oct 21;18(15):2029-38
references.pmid: 15577624
references.citation: N Engl J Med. 2008 May 15;358(20):2107-16
references.pmid: 18480203
references.citation: J Infect Dis. 2012 Jun;205(11):1730-8
references.pmid: 22448010
references.citation: AIDS. 2003 Sep 5;17(13):1881-8
references.pmid: 12960820