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Older HIV-infected patients on antiretroviral therapy have B-cell expansion and attenuated CD4 cell increases with immune activation reduction

Kalayjian, Robert C.a; Spritzler, Johnb; Matining, Roy M.b; Fiscus, Susan A.c; Gross, Barry H.d; Francis, Isaac R.d; Pollard, Richard B.e; Lederman, Michael M.f; Landay, Alang

doi: 10.1097/QAD.0b013e32835fabc2
Clinical Science

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).

Conclusion: Older patients had significant B-cell expansion, higher levels of immune activation markers, and significantly attenuated naive CD4 cell gains associated with activation reduction.

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aMetroHealth Medical Center, Cleveland, Ohio

bHarvard School of Public Health, Boston, Massachusetts

cUniversity of North Carolina School of Medicine, Chapel Hill, North Carolina

dUniversity of Michigan, Ann Arbor, Michigan

eUniversity of California Davis, Sacramento, California

fCase Western Reserve University School of Medicine, Cleveland, Ohio

gRush University School of Medicine, Chicago, Illinois, USA

Correspondence to Robert Charles Kalayjian, MD, MetroHealth Med Ctr, Cleveland, USA. E-mail:

Received 4 December, 2012

Revised 24 January, 2013

Accepted 31 January, 2013

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (

© 2013 Lippincott Williams & Wilkins, Inc.