Skip to main content

Advertisement

Log in

Suppression of human immunodeficiency virus replication in human brain tissue by nucleoside reverse transcriptase inhibitors

  • Short Communication
  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

Human immunodeficiency virus (HIV) infection of the brain is associated pathologically with neuronal damage and loss. Clinically cognitive impairments can develop, which in some can be improved by highly active antiretroviral therapy (HAART), whereas in others, the infection persists despite treatment. The efficacy of antiretrovirals to treat cognitive impairments may be related to their ability to suppress viral replication in the brain and also to prevent neurodegeneration. To investigate this question, the authors assessed the ability of stavudine (300 nM), zidovudine (2 nM), and abacavir (300 nM) to suppress viral replication in human brain tissue aggregates infected with HIV-1 SF162. Aggregates were cultured for 4 weeks and exposed to nucleoside reverse transcriptase inhibitors (NRTIs) either 24 h prior, simultaneously, or 24 h post infection. Viral replication was assessed by p24 enzyme-linked immunosorbent assay (ELISA) in culture medium. The authors observed a statistically significant reduction in the rate of viral replication for stavudine added 24 h prior to infection univariate analysis of variance ([UANOVA], t = 2.55, df = 17, P =.021). Decreased viral replication observed with zidovudine and abacavir was not statistically significant.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Bell JE, Brettle RP, Chiswick A, Simmonds P (1998). HIV encephalitis, proviral load and dementia in drug users and homosexuals with AIDS—effect of neocortical involvement. Brain 121: 2043–2052.

    Article  PubMed  Google Scholar 

  • Chang L, Ernst T, Leonido-Yee M, Whitt M, Speck O, Walot I, Miller EN (1999). Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia. Neurology 53: 782–789.

    CAS  PubMed  Google Scholar 

  • Ellis RJ, Hsia K, Spector SA, Nelson JA, Heaton RK, Wallace MR, Abramson I, Atkinson JH, Grant I, McCutchan JA, the HNRC Group (1997). Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome. Ann Neurol 42: 679–688.

    Article  CAS  PubMed  Google Scholar 

  • Everall IP, Heaton RK, Marcotte TD, Ellis RJ, McCutchan JA, Grant I, Mallory M, Masliah E, HNRC Group (1999). Cortical synaptic density is reduced in mild to moderate human immunodeficiency virus neurocognitive disorder. Brain Pathol 9: 209–217.

    Article  CAS  PubMed  Google Scholar 

  • Everall IP, Luthert PJ, Lantos PL (1991). Neuronal loss in the frontal cortex in HIV infection. Lancet 337: 1119–1121.

    Article  CAS  PubMed  Google Scholar 

  • Foudraine NA, Hoetelmans RMW, Lange JMA, de Wolf F, van Benthem BHB, Maas JJ, Keet IPM, Portegies P (1998). Cerebrospinal fluid HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine and stavudine. Lancet 351: 1547–1551.

    Article  CAS  PubMed  Google Scholar 

  • Hong M, Schlichter L, Bendayan R (2000). A Na(+)-dependent nucleoside transporter in microglia. J Pharmacol Exp Ther 292: 366–374.

    CAS  PubMed  Google Scholar 

  • Kandanearatchi A, Zuckerman M, Smith M, Vyakarnam A, Everall IP (2002). Granulocyte-macrophage colonystimulating factor enhances viral load in human brain tissue: amelioration with stavudine. AIDS 16: 413–420.

    Article  CAS  PubMed  Google Scholar 

  • Limoges J, Persidsky Y, Poluektova L, Rasmussen J, Ratanasuwan W, Zelivyanskaya M, McCernon DR, Lanier ER, Gendelman HE (2000). Evaluation of antiretroviral drug efficacy for HIV-1 encephalitis in SCID mice. Neurology 54: 379–389.

    CAS  PubMed  Google Scholar 

  • Masliah E, Heaton RK, Marcotte TD, Ellis RJ, wiley CA, Mallory M, achim CL, McCutchan A, Nelson JA, Atkinson JH, Grant I, HNRC Group (1997). Dendritic injury is a pathological substrate for HIV related cognitive disorders. Ann Neurol 42: 963–972.

    Article  CAS  PubMed  Google Scholar 

  • Takasawa K, Terasaki T, Suzuki H, Ooie T, Sugiyama Y (1997). Distributed model analysis of 3′-azido-3′-deoxythymidine and 2′,3′-deoxyinosine distribution in brain tissue and cerebrospinal fluid. J Pharmacol Exp Ther 282: 1509–1517.

    CAS  PubMed  Google Scholar 

  • Thomas SA, Segal MB (1998). The transport of the anti-HIV drug, 2′,3′-didehydro-3′-deoxythymidine (D4T), across the blood-brain and blood-cerebrospinal fluid barriers. Br J Pharmacol 125: 49–54.

    Article  CAS  PubMed  Google Scholar 

  • Trillo-Pazos G, Kandanearatchi A, Eyeson J, King D, Vyakarnam A, Everall I (2003). HIV-1 causes neuronal loss and damage in human brain balls: a human 3-D model to investigate the cellular brain of HIV associate dementia. Neuropathol Appl Neurobiol In press.

  • Tozzi V, Balestra P, Galgani S (1999). Positive and sustained effects of highly active antiretroviral therapy on HIV-1 associated neurocognitive impairment. AIDS 13: 1889–1897.

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Brundage RC, Barbhiaiya RH, Sawchuk RJ (1997). Microdialysis studies of the distribution of stavudine into the central nervous system in the freely moving rat. Pharmacol Res 14: 865–872.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Apsara Kandanearatchi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kandanearatchi, A., Vyakarnam, A., Landau, S. et al. Suppression of human immunodeficiency virus replication in human brain tissue by nucleoside reverse transcriptase inhibitors. Journal of NeuroVirology 10, 136–139 (2004). https://doi.org/10.1080/13550280490428379

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/13550280490428379

Keywords

Navigation