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Effect of Age on the CD4+ T-Cell Impairment in HIV-Infected Persons Without and With cART

Allers, Kristina PhD*; Bösel, Diana BTA*; Epple, Hans-Jörg MD*; Karcher, Heiko MD*; Schmidt, Wolfgang MD; Kunkel, Désirée PhD*; Geelhaar-Karsch, Anika PhD*; Schinnerling, Katina PhD*; Moos, Verena PhD*; Schneider, Thomas MD, PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 May 2014 - Volume 66 - Issue 1 - p 7–15
doi: 10.1097/QAI.0000000000000097
Basic and Translational Science

Background: Knowledge about HIV infection in older persons is becoming increasingly important. CD4+ T cells are essential for protective immunity, but little is known about the effect of age on the CD4+ T-cell impairment in HIV infection.

Methods: Treatment-naive patients aged older than 50 or younger than 40 years were studied for absolute and relative frequencies of CD31+ naive and CD31 naive CD4+ T cells, central memory, effector memory, and terminally differentiated CD4+ T cells, and compared with age-matched controls. In addition, cellular proliferation and cytokine secretion properties were determined. CD4+ T-cell reconstitution was analyzed in older and younger patients with <350 or ≥350 CD4+ T cells per microliter at initiation of combination antiretroviral tharapy (cART).

Results: CD4+ T cells of older but not younger HIV-infected patients showed age-inappropriate low levels of CD31 naive cells, increased levels of effector memory cells, and enhanced interferonγ and interleukin-17 secretion. Impaired CD4+ T-cell composition persisted in patients who initiated cART at <350 CD4+ T cells per microliter. In patients with CD4+ T cells ≥350 per microliter, alterations were less pronounced and were reversible with cART. Compared with age-matched controls, total CD4+ T-cell counts did not differ between treated younger and older HIV-infected patients.

Conclusions: These data demonstrate that aging enhances the CD4+ T-cell impairment in HIV-infected persons mainly by a loss of CD31 naive cells, accumulation of effector memory cells, and increased pro-inflammatory effector functions. Age-related changes in CD4+ T-cell composition can be prevented by an early initiation of cART.

*Department of Gastroenterology, Infectious Diseases, and Rheumatology, Medical Clinic I, Campus Benjamin Franklin, Charité—University Medicine Berlin, Berlin, Germany; and

Ärzteforum Seestraβe, Berlin, Germany (Heiko Karcher is now with Ärzteforum Praxis City Ost, Berlin, Germany; Desiree Kunkel is now with Berlin–Brandenburg Center for Regenerative Therapies, Campus Virchow Klinikum, Charité—University Medicine Berlin, Berlin, Germany).

Correspondence to: Kristina Allers, PhD, Department of Gastroenterology, Infectious Diseases, and Rheumatology, Medical Clinic I, Campus Benjamin Franklin, Charité, Hindenburgdamm 30, 12203 Berlin, Germany (e-mail: kristina.allers@charite.de).

Supported by research funding from the Deutsche Forschungsgemeinschaft (German Research Foundation, grant SCHN 616/6-1).

The authors have no conflicts of interest to disclose.

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 Web site (www.jaids.com).

Received December 18, 2013

Accepted December 18, 2013

© 2014 by Lippincott Williams & Wilkins