Impaired response to HAART in HIV-infected individuals with high autonomic nervous system activity

doi:10.1073/pnas.221134198

Impaired response to HAART in HIV-infected individuals with high autonomic nervous system activity

Departments of ^*Medicine, ^‡‡Microbiology, Immunology, and Molecular Genetics, ^§Psychiatry and Biobehavioral Sciences, and ^‖Psychology, University of California, Los Angeles, CA 90095; ^†University of California Los Angeles AIDS Institute, Los Angeles, CA 90095; ^¶Veterans Administration Greater Los Angeles Area Healthcare System, Los Angeles, CA 90073; and ^**Consolidated Laboratory Services, 7855 Haskill Avenue, Suite 302, Van Nuys, CA 91406

Edited by John M. Coffin, Tufts University School of Medicine, Boston, MA, and approved August 27, 2001 (received for review March 19, 2001)

Abstract

Neurotransmitters can accelerate HIV-1 replication in vitro, leading us to examine whether differences in autonomic nervous system (ANS) activity might promote residual HIV-1 replication in patients treated with highly active antiretroviral therapy. Patients who showed constitutively high levels of ANS activity before highly active antiretroviral therapy experienced poorer suppression of plasma viral load and poorer CD4⁺ T cell recovery over 3–11 months of therapy. ANS activity was not related to demographic or behavioral characteristics that might influence pathogenesis. However, the ANS neurotransmitter norepinephrine enhanced replication of both CCR5- and CXCR4-tropic strains of HIV-1 in vitro via chemokine receptor up-regulation and enhanced viral gene expression, suggesting that neural activity may directly promote residual viral replication.

Footnotes

↵ ‡ To whom reprint requests should be addressed. E-mail: coles{at}nicco.sscnet.ucla.edu.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

ANS,

autonomic nervous system;

PKA,

protein kinase A;

HAART,

highly active antiretroviral therapy;

PBMC,

peripheral blood mononuclear cells;

PHA,

phytohemagglutinin