Impact of highly active antiretroviral therapy initiation on CD4R T-cell repopulation in duodenal and rectal mucosa

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 (P1/40.02, 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 (P1/40.0015, 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.