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

TitleOlder HIV-infected patients on antiretroviral therapy have B-cell expansion and attenuated CD4 cell increases with immune activation reduction.
Publication TypeJournal Article
Year of Publication2013
AuthorsKalayjian RC, Spritzler J, Matining RM, Fiscus SA, Gross BH, Francis IR, Pollard RB, Lederman MM, Landay A
JournalAIDS
Volume27
Issue10
Pagination1563-71
Date Published2013 Jun 19
ISSN1473-5571
KeywordsAdolescent, Adult, Age Factors, Aging, Anti-HIV Agents, Antigens, CD38, B-Lymphocytes, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Drug Therapy, Combination, Female, HIV Infections, HLA-DR Antigens, Humans, Male, Middle Aged, Prospective Studies, Receptors, Tumor Necrosis Factor, Type II, Young Adult
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).

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.

DOI10.1097/QAD.0b013e32835fabc2
Alternate JournalAIDS
PubMed ID24047762
PubMed Central IDPMC3805132
Grant ListAI-069501 / AI / NIAID NIH HHS / United States
AI-36219 / AI / NIAID NIH HHS / United States
AI-68634 / AI / NIAID NIH HHS / United States
AI-68636 / AI / NIAID NIH HHS / United States
P30 AI036219 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States