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.
The effects of HAART on the gastrointestinal (GI) 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 GI tract region studied.
We obtained blood, rectal biopsies, and duodenal biopsies from
fourteen chronically infected individuals at baseline and at four to nine
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.
CD4+ T-cell percentages increased significantly in blood, rectal, and
duodenal mucosa after four to nine 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, while PD-1
expression on blood HIV-specific CD4+ and CD8+ T-cells decreased.
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.