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

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Abstract

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.

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