Modeling brain lentiviral infections during antiretroviral therapy in AIDS

Weston C. Roda, Michael Y. Li, Michael S. Akinwumi, Eugene L. Asahchop, Benjamin Gelman, Kenneth W. Witwer, Christopher Power

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Understanding HIV-1 replication and latency in different reservoirs is an ongoing challenge in the care of patients with HIV/AIDS. A mathematical model was created to describe and predict the viral dynamics of HIV-1 and SIV infection within the brain during effective combination antiretroviral therapy (cART). The mathematical model was formulated based on the biology of lentiviral infection of brain macrophages and used to describe the dynamics of transmission and progression of lentiviral infection in brain. Based on previous reports quantifying total viral DNA levels in brain from HIV-1 and SIV infections, estimates of integrated proviral DNA burden were made, which were used to calibrate the mathematical model predicting viral accrual in brain macrophages from primary infection. The annual rate at which susceptible brain macrophages become HIV-1 infected was estimated to be 2.90×10−7–4.87×10−6 per year for cART-treated HIV/AIDS patients without comorbid neurological disorders. The transmission rate for SIV infection among untreated macaques was estimated to be 5.30×10−6–1.37×10−5 per year. An improvement in cART effectiveness (1.6–48%) would suppress HIV-1 infection in patients without neurological disorders. Among patients with advanced disease, a substantial improvement in cART effectiveness (70%) would eradicate HIV-1 provirus from the brain within 3–32 (interquartile range 3–9) years in patients without neurological disorders, whereas 4–51 (interquartile range 4–16) years of efficacious cART would be required for HIV/AIDS patients with comorbid neurological disorders. HIV-1 and SIV provirus burdens in the brain increase over time. A moderately efficacious antiretroviral therapy regimen could eradicate HIV-1 infection in the brain that was dependent on brain macrophage lifespan and the presence of neurological comorbidity.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalJournal of NeuroVirology
DOIs
StateAccepted/In press - May 16 2017

Keywords

  • Brain macrophage
  • Combination antiretroviral therapy (cART)
  • HIV-1
  • Mathematical model
  • SIV
  • Viral dynamics

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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  • Cite this

    Roda, W. C., Li, M. Y., Akinwumi, M. S., Asahchop, E. L., Gelman, B., Witwer, K. W., & Power, C. (Accepted/In press). Modeling brain lentiviral infections during antiretroviral therapy in AIDS. Journal of NeuroVirology, 1-10. https://doi.org/10.1007/s13365-017-0530-3