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

Paula Lerner, Moraima Guadalupe, Richard Donovan, Jason Hung, Jason Flamm, Thomas P Prindiville, Sumathi Sankaran-Walters, Michael Syvanen, Joseph K. Wong, Michael D. George, Satya Dandekar

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Abstract

Interruption of suppressive highly active antiretroviral therapy (HAART) in HIV-infected patients leads to increased HIV replication and viral rebound in peripheral blood. Effects of therapy interruption on gut-associated lymphoid tissue (GALT) have not been well investigated. We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that 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. A rapid increase in viral loads with a modest decline of CD4 + T cells in peripheral blood was observed, while gut mucosal CD4 + T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients. Sequence analysis of rebound virus suggested that GALT was not the major contributor to the postinterruption plasma viremia nor were GALT HIV reservoirs rapidly replaced by HIV rebound variants. Our data suggest an early establishment and persistence of viral reservoirs in GALT with minimal diversity. 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.

Original languageEnglish (US)
Pages (from-to)4772-4782
Number of pages11
JournalJournal of Virology
Volume85
Issue number10
DOIs
StatePublished - May 2011

Fingerprint

Viremia
viremia
Highly Active Antiretroviral Therapy
Lymphoid Tissue
digestive system
HIV
therapeutics
HIV Infections
HIV infections
Secondary Prevention
T-Lymphocytes
T-lymphocytes
Sequence Analysis
Gene Expression
sequence analysis
Viral Load
gene expression
Interferons
Antiviral Agents
blood

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

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. / Lerner, Paula; Guadalupe, Moraima; Donovan, Richard; Hung, Jason; Flamm, Jason; Prindiville, Thomas P; Sankaran-Walters, Sumathi; Syvanen, Michael; Wong, Joseph K.; George, Michael D.; Dandekar, Satya.

In: Journal of Virology, Vol. 85, No. 10, 05.2011, p. 4772-4782.

Research output: Contribution to journalArticle

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