November 13, 2024

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Study Finds Rare HIV-Infected Individuals Can Avoid Disease Progression Without Antiviral Treatment

Study Finds Rare HIV-Infected Individuals Can Avoid Disease Progression Without Antiviral Treatment



Study Finds Rare HIV-Infected Individuals Can Avoid Disease Progression Without Antiviral Treatment

Study Finds Rare HIV-Infected Individuals Can Avoid Disease Progression Without Antiviral Treatment.

A recent article published in MED titled “Genetic and Immune Features in Viremic Non-Progressors Prevent HIV-1 Disease Progression” explores a rare group of HIV-infected individuals known as Viremic Non-Progressors (VNPs).

These individuals maintain healthy immune function and prevent disease progression without the need for antiretroviral therapy (ART).

Study Finds Rare HIV-Infected Individuals Can Avoid Disease Progression Without Antiviral Treatment

 


Key Findings

The study reveals that VNPs exhibit superior gut health, lower immune activation, and unique genetic and immunological features that provide resistance to HIV progression. This discovery offers valuable insights that could lead to new therapeutic approaches for managing HIV and enhancing immune recovery in infected individuals.


What Are Viremic Non-Progressors (VNPs)?

VNPs represent a unique and rare subset of HIV-infected individuals who maintain stable CD4+ T-cell counts and avoid developing AIDS, despite high levels of viral replication in their blood. Unlike elite controllers (ECs)—patients whose immune systems suppress HIV to undetectable levels—VNPs still exhibit measurable viral loads but remain asymptomatic without ART.

VNPs make up less than 0.1% of the global HIV-positive adult population. In comparison to typical progressors whose disease advances to AIDS without treatment, VNPs can maintain long-term immune stability with minimal clinical intervention.


Role of the CCR5 Gene

The study conducted single-cell and multi-omics analyses on 16 VNPs and 29 progressors, identifying critical genetic factors that distinguish the two groups. Notably, VNPs were found to carry the CCR5-Δ32 gene mutation more frequently (53.8% heterozygous) compared to progressors (16.0%).

This mutation reduces the expression of CCR5 receptors on CD4+ T cells, which HIV uses to enter host cells, thus lowering the susceptibility to infection and viral progression.


Immune System Characteristics of VNPs

VNPs demonstrate several immune-related advantages, including:

  1. Lower Chronic Inflammation:

    • VNPs avoid chronic immune activation and cellular exhaustion, maintaining healthier immune function.
    • Single-cell RNA sequencing revealed reduced expression of interferon-stimulated genes across multiple immune cell types, including CD4+, CD8+, and NK cells. This prevents overactive inflammatory responses typically triggered by HIV replication.
  2. Higher Proportions of Naïve CD8+ T Cells:

    • VNPs exhibit more naïve CD8+ T cells—those that haven’t yet encountered antigens—while having fewer activated memory CD8+ T cells, reducing immune overactivation.
  3. Better Gut Health:

    • VNPs showed lower levels of sialic acid, a marker for gut barrier damage, suggesting healthier intestinal mucosa compared to progressors.
    • They also had reduced levels of kynurenine, a metabolite linked to immune activation and CD4+ T-cell depletion.

Implications for Future Treatments

By maintaining low immune activation and avoiding chronic inflammation, VNPs effectively prevent HIV from progressing to AIDS without ART. These findings underscore the potential for developing new interventions aimed at enhancing natural immune defenses in HIV patients.

Further research into the genetic and immune mechanisms behind VNPs’ resistance may pave the way for innovative therapies to restore immune function in a broader population of people living with HIV.

Study Finds Rare HIV-Infected Individuals Can Avoid Disease Progression Without Antiviral Treatment

Reference:

Host genetic and immune factors drive evasion of HIV-1 pathogenesis in viremic non-progressors

DOI:10.1016/j.medj.2024.09.007

(source:internet, reference only)


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