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The central nervous system is a viral reservoir in simian immunodeficiency virus-infected macaques on combined antiretroviral therapy: A model for human immunodeficiency virus patients on highly active antiretroviral therapy

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Abstract

This study used a simian immunodeficiency virus (SIV)-macaque model to determine whether virus persists in the central nervous system (CNS) of human immunodeficiency virus (HIV)-infected individuals in which plasma viral load has been suppressed by highly active antiretroviral therapy. SIV-infected macaques were treated with two reverse transcriptase inhibitors: PMPA (9-R-(2-phosphonomethoxypropyl)adenine), which does not cross the blood-brain barrier, and FTC (beta-2′,3′-dideoxy-3′-thia-5-fluorocytidine), which does. Viral DNA and RNA were quantitated in the brain after 6 months of suppression of virus replication in blood and cerebrospinal fluid (CSF). Viral DNA was detected in brain from all macaques, including those in which peripheral viral replication had been suppressed either by antiretroviral therapy or host immune responses. Significant neurological lesions were observed only in one untreated macaque that had active virus replication in the CNS. Expression of the inflammatory markers, major histocompatibility complex (MHC) II and CD68 was significantly lower in macaques treated with PMPA/FTC. Thus, although antiretroviral treatment may suppress virus replication in the periphery and the brain and reduce CNS inflammation, viral DNA persists in the brain despite treatment. This suggests that the brain may serve as a long-term viral reservoir in HIV-infected individuals treated with antiretroviral drugs that suppress virus replication.

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Authors and Affiliations

  1. Retrovirus Laboratory, Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Janice E. Clements, Ming Li, Lucio Gama, Brandon Bullock, Lucy M. Carruth, Joseph L. Mankowski & M. Christine Zink

  2. 733 N. Broadway, Broadway Research Building, 819, 21205, Baltimore, MD, USA

    Janice E. Clements

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  1. Janice E. Clements
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  2. Ming Li
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  3. Lucio Gama
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  4. Brandon Bullock
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  5. Lucy M. Carruth
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  6. Joseph L. Mankowski
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  7. M. Christine Zink
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Correspondence to Janice E. Clements.

Additional information

This work was supported by grants to JEC (MH07036, NS047984) and MCZ (NS44815, MH069116).

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Clements, J.E., Li, M., Gama, L. et al. The central nervous system is a viral reservoir in simian immunodeficiency virus-infected macaques on combined antiretroviral therapy: A model for human immunodeficiency virus patients on highly active antiretroviral therapy. Journal of NeuroVirology 11, 180–189 (2005). https://doi.org/10.1080/13550280590922748-1

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  • DOI: https://doi.org/10.1080/13550280590922748-1

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