Back to Search Start Over

Irreversible depletion of intestinal CD4+ T cells is associated with T cell activation during chronic HIV infection.

Authors :
Asowata OE
Singh A
Ngoepe A
Herbert N
Fardoos R
Reddy K
Zungu Y
Nene F
Mthabela N
Ramjit D
Karim F
Govender K
Ndung'u T
Porterfield JZ
Adamson JH
Madela FG
Manzini VT
Anderson F
Leslie A
Kløverpris HN
Source :
JCI insight [JCI Insight] 2021 Nov 22; Vol. 6 (22). Date of Electronic Publication: 2021 Nov 22.
Publication Year :
2021

Abstract

HIV infection in the human gastrointestinal (GI) tract is thought to be central to HIV progression, but knowledge of this interaction is primarily limited to cohorts within Westernized countries. Here, we present a large cohort recruited from high HIV endemic areas in South Africa and found that people living with HIV (PLWH) presented at a younger age for investigation in the GI clinic. We identified severe CD4+ T cell depletion in the GI tract, which was greater in the small intestine than in the large intestine and not correlated with years on antiretroviral treatment (ART) or plasma viremia. HIV-p24 staining showed persistent viral expression, particularly in the colon, despite full suppression of plasma viremia. Quantification of mucosal antiretroviral (ARV) drugs revealed no differences in drug penetration between the duodenum and colon. Plasma markers of gut barrier breakdown and immune activation were elevated irrespective of HIV, but peripheral T cell activation was inversely correlated with loss of gut CD4+ T cells in PLWH alone. T cell activation is a strong predictor of HIV progression and independent of plasma viral load, implying that the irreversible loss of GI CD4+ T cells is a key event in the HIV pathogenesis of PLWH in South Africa, yet the underlying mechanisms remain unknown.

Details

Language :
English
ISSN :
2379-3708
Volume :
6
Issue :
22
Database :
MEDLINE
Journal :
JCI insight
Publication Type :
Academic Journal
Accession number :
34618690
Full Text :
https://doi.org/10.1172/jci.insight.146162