Impaired CD4+ T-Cell Restoration in the Small Versus Large Intestine of HIV-1–Positive South Africans Receiving Combination Antiretroviral Therapy

E Cassol, S Malfeld, P Mahasha, R Bond… - The Journal of …, 2013 - academic.oup.com
E Cassol, S Malfeld, P Mahasha, R Bond, T Slavik, C Seebregts, G Poli, S Cassol…
The Journal of infectious diseases, 2013academic.oup.com
Background. 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. Methods. Thirty-
eight patients with advanced HIV-1 infection who had chronic diarrhea (duration,> 4 weeks) …
Abstract
Background.  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.
Methods.  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.
Results.  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.
Conclusions.  Strategies that target inflammation and immune activation in the small intestine may be required to expedite CD4+ T-cell recovery and improve therapeutic outcomes.
Oxford University Press