Skip Navigation LinksHome > March 27, 2013 - Volume 27 - Issue 6 > Impact of highly active antiretroviral therapy initiation on...
doi: 10.1097/QAD.0b013e32835d85b4
Basic Science

Impact of highly active antiretroviral therapy initiation on CD4+ T-cell repopulation in duodenal and rectal mucosa

Hayes, Timothy L.a; Asmuth, David M.b; Critchfield, J. Williama; Knight, Thomas H.b; McLaughlin, Bridget E.a; Yotter, Tammyb; McConnell, Delandy H.a; Garcia, Juan Carlosc; Pollard, Richard B.b; Shacklett, Barbara L.a,b

Collapse Box


Objective: The objective of this study was to assess the effects of HAART initiation on CD4+ T-cell repopulation and T-cell immune activation in rectal and duodenal mucosa.

Design: The effects of HAART on the gastrointestinal tract remain controversial, and studies have reached different conclusions regarding its effectiveness at restoring mucosal CD4+ T cells depending upon time of initiation, duration of treatment and gastrointestinal tract region studied.

Methods: We obtained blood, rectal biopsies and duodenal biopsies from 14 chronically infected individuals at baseline and at 4–9 months post-HAART initiation. We examined CD4+ T-cell frequencies in blood, rectum and duodenum at both time points, and performed a detailed assessment of CD4+ T-cell phenotype, immune activation marker expression and HIV-specific CD8+ T-cell responses in blood and rectal mucosa.

Results: CD4+ T-cell percentages increased significantly in blood, rectal and duodenal mucosa after 4–9 months of HAART (P = 0.02, 0.0005, 0.0002), but remained lower than in uninfected controls. HIV-specific CD8+ T-cell responses in blood and rectal mucosa declined following HAART initiation (P = 0.0015, 0.021). CD8+ T-cell coexpression of CD38 and HLA-DR in blood and mucosa, as well as plasma sCD14, declined significantly. CD28 expression on blood and mucosal CD8+ T cells increased, whereas programmed death receptor-1 expression on blood HIV-specific CD4+ and CD8+ T cells decreased.

Conclusion: Within the first months of HAART, limited CD4+ T-cell reconstitution occurs in small and large intestinal mucosa. Nevertheless, decreased immune activation and increased CD28 expression suggest rapid immunological benefits of HAART despite incomplete CD4+ T-cell reconstitution.

© 2013 Lippincott Williams & Wilkins, Inc.


Article Tools


Article Level Metrics

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.