1. ¹Department of Medicine, University of Toronto, Toronto, Ontario, Canada
2. ²Department of Immunology, University of Toronto, Toronto, Ontario, Canada
3. ³Canadian Immunodeficiency Research Collaborative, Toronto, Ontario, Canada
4. ⁴Laboratory of Immunoregulation and Office of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
5. ⁵Division of Gastroenterology, St Michael's Hospital, Toronto, Ontario, Canada
6. ⁶Department of Medicine, University Health Network, Toronto, Ontario, Canada

Correspondence: PM Sheth, (prameet.sheth@utoronto.ca)

Received 26 September 2007; Accepted 1 May 2008; Published online 2 July 2008.

Abstract

Early and profound CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) may drive Human Immunodeficiency Virus (HIV) immunopathogenesis, and GALT immune reconstitution on highly active antiretroviral therapy (HAART) may be suboptimal. Blood and sigmoid colon biopsies were collected from HAART-treated individuals with undetectable blood HIV RNA for 4 years and from uninfected controls. HIV proviral levels and T-cell phenotype/function were examined in both compartments. CD4+ T-cell reconstitution in the sigmoid, including CD4+ T cells expressing CCR5, exceeded that in blood and did not differ from uninfected controls. Sigmoid HIV proviral load was not correlated with CD4+ reconsitution, but was correlated with the degree of mucosal CD8+ T-cell immune activation. Colonic Gag-specific T-cell responses were common, but were not associated with proviral load or immune activation. In this select study population, long-term HAART was associated with complete CD4+ T-cell reconstitution in sigmoid colon. However, colonic immune activation may drive ongoing HIV replication.