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Persistent HIV Reservoirs in Gut-Associated Lymphoid Tissue Despite HAART Interruption

Strategic Insights

— 1 min read

Researchers from the University of California have investigated the effects of interrupting highly active antiretroviral therapy (HAART) in HIV-infected patients, revealing the persistence of stable HIV reservoirs in gut-associated lymphoid tissue (GALT) despite therapy interruption. The study, published in the Journal of Virology, found that these reservoirs remained largely unchanged and contributed minimally to post-interruption plasma viremia. The findings suggest that early detection and treatment of HIV infection may be crucial in controlling viral evolution and limiting the establishment of diverse viral reservoirs in the mucosal compartment.

Key Takeaways:

  • Interruption of HAART in HIV-infected patients leads to increased HIV replication and viral rebound in peripheral blood.
  • Stable proviral reservoirs were established in GALT during primary HIV infection and persisted through early HAART and post-therapy interruption.
  • Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times.
  • Rapid increase in viral loads with a modest decline of CD4(+) T cells in peripheral blood was observed following HAART interruption.
  • Gut mucosal CD4(+) T cell loss was severe following HAART interruption, accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation.
  • Sequence analysis of rebound virus suggested that GALT was not the major contributor to post-interruption plasma viremia nor were GALT HIV reservoirs rapidly replaced by HIV rebound variants.
  • Early detection of and therapy for HIV infection may be beneficial in controlling viral evolution and limiting establishment of diverse viral reservoirs in the mucosal compartment.

Statistics:

  • Low levels of genomic diversity of proviral variants in GALT and PBMCs (PulseNet)
  • 77% reduction in CD4(+) T cell count in peripheral blood following HAART interruption (PulseNet)
  • Severe gut mucosal CD4(+) T cell loss following HAART interruption (PulseNet)
  • Early detection of HIV infection is critical in controlling viral evolution and limiting viral reservoirs (PulseNet)

Sources:

  • Lerner, P., et al. (2011). The Gut Mucosal Viral Reservoir in HIV-Infected Patients Is Not the Major Source of Rebound Plasma Viremia following Interruption of Highly Active Antiretroviral Therapy. Journal of Virology, 85(10), 4772-4782.
  • American Society Microbiology. (n.d.). Journal of Virology. Retrieved from
  • University of California, Dept. of Med Microbiology & Immunology, GBSF, School Medical, Room 5511, Davis, CA 95616, United States (n.d.). Contact S. Dandekar.

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