Early antiretroviral treatment prevents the development of central nervous system abnormalities in simian immunodeficiency virus-infected rhesus monkeys.
OBJECTIVE
Neurocognitive disorders are devastating consequences of HIV infection. Although antiretroviral regimens have been efficacious in both improving life expectancy and decreasing dementia, there has not been an effect on the overall prevalence of HIV-associated neurocognitive disorders. Whether early institution of treatment, or treatment with drugs that effectively penetrate the blood-brain barrier, would help protect from such conditions is not known. Using the simian immunodeficiency virus/macaque model, we investigated the hypothesis that early introduction of antiretroviral treatment can protect the brain.


METHODS
Animals were inoculated with simian immunodeficiency virus, and upon resolution of the acute infection period divided into two groups and treated, or not, with combination antiretroviral therapy. Viral, immune, and physiological parameters were measured during the course of infection, followed by assessment of viral, immune, and molecular parameters in the brain.


RESULTS
We observed that even with agents that show poor penetration into the central nervous system, early antiretroviral treatment prevented characteristic neurophysiological and locomotor alterations arising after infection and resulted in a significant decrease in brain viral load. Although the number of infiltrating immune cells in the brain did not change with treatment, their phenotype did, favoring an enrichment of effector T cells. Early treatment also significantly lowered brain levels of interferon-alpha, a cytokine that can lead to neurocognitive and behavioral alterations.


CONCLUSIONS
Early antiretroviral treatment prevents central nervous system dysfunction by decreasing brain viral load and interferon-alpha levels, which can have a profound impact over the course of infection.
Marcondes
Maria Cecilia G
MC
Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, California, USA.
Flynn
Claudia
C
Huitron-Rezendiz
Salvador
S
Watry
Debbie D
DD
Zandonatti
Michelle
M
Fox
Howard S
HS
D015526:AIDS Dementia Complex / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D001921:Brain / Q000276:immunology / Q000821:virology; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007156:Immunologic Memory / Q000187:drug effects; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000187:drug effects; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013686:Telemetry / Q000379:methods; D019562:Viral Load
D019380:Anti-HIV Agents