We aimed to characterize the impact of antiretroviral therapy (ART) initiation on gastrointestinal-associated lymphoid tissue at various sites along the gastrointestinal site.
Peripheral blood and duodenal and rectal biopsies were obtained from 12 HIV− to 33 treatment-naive HIV+ participants at baseline and after 9 months ART. Tissue was digested for immunophenotyping. Inflammatory, bacterial translocation and intestinal damage markers were measured in plasma.
Twenty-six HIV+ patients completed follow-up. The lowest reconstitution of CD4+ T cells and the lowest CD4+/CD8+ ratio during ART compared with blood were observed in the duodenum with the rectum being either intermediate or approaching blood levels. Regulatory T cells were in higher proportions in the duodenum than the rectum and neither declined significantly during ART. Several correlations with biomarkers of microbial translocation were observed including increases in lipoteichoic acid levels, which reflects Gram-positive bacterial translocation, correlated with increases in %CD4+ T cells in the duodenum (Rho 0.773, P = 0.033), and with decreases in duodenal regulatory T-cell populations (Rho −0.40, P = 0.045).
HIV-mediated immunological disruption is greater in the duodenum than rectum and blood before and during ART. Small intestine damage may represent a unique environment for T-cell depletion, which might be attenuated by interaction with Gram-positive bacteria.
aDepartment of Pediatrics, La Paz University Hospital and Research Institute (ldiPAZ), Madrid
bDepartment of Infectious Diseases, Ramon y Cajal University Hospital and Research Institute (IRYCIS), Faculty of Medicine, University of Alcalá, Alcalá, Spain
cUniversity of California Davis Medical Center, Sacramento
dCalifornia National Primate Research Center, Davis, California
eUniversity of Texas Medical Branch, Galveston, Texas
fSchool of Pharmacy, University of North Carolina, Chapel Hill, North Carolina
gLaboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
hRush University Medical Center, Chicago, Illinois
iVeterans Administration Northern California Health Care System, Mather
jUniversity of California, San Francisco, San Francisco, California, USA.
Correspondence to David M. Asmuth, University of California Davis Medical Center, Sacramento, California, USA. Tel: +1 916 734 8695; fax: +1 916 734 7766; e-mail: email@example.com
Received 10 February, 2019
Revised 29 May, 2019
Accepted 15 July, 2019
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