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Initiation of antiretroviral therapy before detection of colonic infiltration by HIV reduces viral reservoirs, inflammation and immune activation

Authors :
Crowell, Trevor A.
Fletcher, James L.K.
Sereti, Irini
Pinyakorn, Suteeraporn
Dewar, Robin
Krebs, Shelly J.
Chomchey, Nitiya
Rerknimitr, Rungsun
Schuetz, Alexandra
Michael, Nelson L.
Phanuphak, Nittaya
Chomont, Nicolas
Ananworanich, Jintanat
Source :
Journal of the International AIDS Society. September, 2016, Vol. 19 Issue 3
Publication Year :
2016

Abstract

Introduction: Colonic infiltration by HIV occurs soon after infection, establishing a persistent viral reservoir and a barrier to cure. We investigated virologic and immunologic correlates of detectable colonic HIV RNA during acute HIV infection (AHI) and their response to antiretroviral treatment (ART). Methods: From 49,458 samples screened for HIV, 74 participants were enrolled during AHI and 41 consented to optional sigmoidoscopy, HIV RNA was categorized as detectable ([greater than or equal to] 50 copies/mg) or undetectable in homogenized colon biopsy specimens. Biomarkers and HIV burden in blood, colon and cerebrospinal fluid were compared between groups and after 24 weeks of ART. Results: Colonic HIV RNA was detectable in 31 participants (76%) and was associated with longer duration since HIV exposure (median 16 vs. 11 days, p =0.02), higher median plasma levels of cytokines and inflammatory markers (CXCL10 476 vs. 148 pg/mL, p =0.02; TNF-RII 1036 vs. 649 pg/mL, p Conclusions: The presence of detectable colonic HIV RNA at the time of ART initiation during AHI is associated with higher levels of proviral DNA after 24 weeks of treatment. Seeding of HIV in the gut may have long-lasting effects on the size of persistent viral reservoirs and may represent an important therapeutic target in eradication strategies. Keywords: HIV; inflammation; CD4 lymphocyte count; highly active antiretroviral therapy; virus latency; infectious disease reservoirs. To access the supplementary material to this article please see Supplementary Files under Article Tools online.<br />Introduction The gut-associated lymphoid tissue (GALT) is one of the first sites infiltrated by HIV during acute infection [1,2] and represents a major reservoir of latently infected cells that create [...]

Details

Language :
English
ISSN :
17582652
Volume :
19
Issue :
3
Database :
Gale General OneFile
Journal :
Journal of the International AIDS Society
Publication Type :
Academic Journal
Accession number :
edsgcl.468335680
Full Text :
https://doi.org/10.7448/IAS.19.1.21163