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

AI Article Synopsis

  • - The study focuses on a large group of people living with HIV (PLWH) in South Africa, highlighting that they often seek help for gastrointestinal (GI) issues at a younger age compared to those in Western countries.
  • - Researchers found significant depletion of CD4+ T cells in the GI tract, particularly in the small intestine, and observed persistent HIV presence in the colon even when plasma viral loads were suppressed.
  • - Elevated markers indicating gut barrier dysfunction and immune activation were present in PLWH, with T cell activation levels being linked to the loss of CD4+ T cells in the gut, suggesting that this loss is critical to HIV progression in these individuals.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8663780PMC
http://dx.doi.org/10.1172/jci.insight.146162DOI Listing

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