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

Osaretin E. Asowata, Alveera Singh, Abigail Ngoepe, Nicholas Herbert, Rabiah Fardoos, Kavidha Reddy, Yenzekile Zungu, Faith Nene, Ntombifuthi Mthabela, Dirhona Ramjit, Farina Karim, Katya Govender, Thumbi Ndung’u, J. Zachary Porterfield, John H. Adamson, Fusi G. Madela, Vukani T. Manzini, Frank Anderson, Alasdair Leslie, Henrik N. Kløverpris

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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.

Original languageEnglish
Article numbere146162
JournalJCI insight
Issue number22
StatePublished - Nov 22 2021

Bibliographical note

Funding Information:
HNK is supported by the Wellcome Trust (202485/Z/16/Z) and the National Institute of Health (NIH) (R01DK126545). AL is supported by the Wellcome Trust (210662/Z/18/Z). This work was supported through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE), a DELTAS Africa Initiative (grant no. DEL-15-006). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences’ (AAS’s) Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (grant no. 107752/Z/15/Z) and the United Kingdom government. The views expressed in this publication are those of the authors and not necessarily those of AAS, NEPAD Agency, Wellcome Trust, or the United Kingdom government. HK and AS were supported by SANTHE.

Publisher Copyright:
Copyright: © 2021, Asowata et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.

ASJC Scopus subject areas

  • Medicine (all)


Dive into the research topics of 'Irreversible depletion of intestinal CD4+ T cells is associated with T cell activation during chronic HIV infection'. Together they form a unique fingerprint.

Cite this