The Journal of infectious diseases, 01 October 2013, Vol.208(7), pp.1113-22
Human immunodeficiency virus type 1 (HIV-1) infection is associated with a massive depletion of intestinal CD4(+) T cells that is only partially reversed by combination antiretroviral therapy (cART). Here, we assessed the ability of nucleoside reverse-transcriptase inhibitor/nonnucleoside reverse-transcriptase inhibitor treatment to restore the CD4(+) T-cell populations in the intestine of South African patients with AIDS. Thirty-eight patients with advanced HIV-1 infection who had chronic diarrhea (duration, 〉4 weeks) and/or unintentional weight loss (〉10% decrease from baseline) of uncertain etiology were enrolled. Blood specimens were collected monthly, and gastrointestinal tract biopsy specimens were collected before cART initiation (from the duodenum, jejunum, ileum, and colon), 3 months after cART initiation (from the duodenum), and 6 months after cART initiation (from the duodenum and colon). CD4(+), CD8(+), and CD38(+)CD8(+) T cells were quantified by flow cytometry and immunohistochemistry analyses, and the HIV-1 RNA load was determined by the Nuclisens assay. CD4(+) T-cell and HIV-1 RNA levels were significantly lower, whereas CD8(+) T-cell levels, including activated CD38(+)CD8(+) T cell levels, were higher in the duodenum and jejunum, compared with the colon. After 6 months of cART, a significant but incomplete recovery of CD4(+) T cells was detected in the colon and peripheral blood but not in the duodenum. Failed restoration of the CD4(+) T-cell count in the duodenum was associated with nonspecific enteritis and CD8(+) T-cell activation. Strategies that target inflammation and immune activation in the small intestine may be required to expedite CD4(+) T-cell recovery and improve therapeutic outcomes.
Africa ; Cd4 Reconstitution ; HIV-1 ; Antiretroviral Therapy ; Immune Activation ; Intestine ; Anti-Retroviral Agents -- Therapeutic Use ; Cd4-Positive T-Lymphocytes -- Immunology ; HIV Infections -- Drug Therapy ; Intestinal Mucosa -- Immunology ; Intestine, Large -- Immunology ; Intestine, Small -- Immunology
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