Advertisement

Journal of NeuroVirology

, Volume 16, Issue 1, pp 25–32 | Cite as

Effects of nadir CD4 count and duration of human immunodeficiency virus infection on brain volumes in the highly active antiretroviral therapy era

  • Ronald A. CohenEmail author
  • Jaroslaw Harezlak
  • Giovanni Schifitto
  • George Hana
  • Uraina Clark
  • Assawin Gongvatana
  • Robert Paul
  • Michael Taylor
  • Paul Thompson
  • Jeffery Alger
  • Mark Brown
  • Jianhui Zhong
  • Thomas Campbell
  • Elyse Singer
  • Eric Daar
  • Deborah McMahon
  • Yuen Tso
  • Constantin T. Yiannoutsos
  • Bradford NaviaEmail author
  • HIV Neuroimaging Consortium
Article

Abstract

Cerebral atrophy is a well-described, but poorly understood complication of human immunodeficiency virus (HIV) infection. Despite reduced prevalence of HIV-associated dementia in the highly active antiretroviral therapy (HAART) era, HIV continues to affect the brains of patients with chronic infection. In this study we examine patterns of brain volume loss in HIV-infected patients on HAART, and demographic and clinical factors contributing to brain volume loss. We hypothesized that nadir CD4+ lymphocyte count, duration of HIV infection, and age would be associated with reduced cortical volumes. Volumes of cortical and subcortical regions in 69 HIV-infected neuroasymptomatic (NA) individuals and 13 with at least mild acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) were measured using voxel-based morphometry. Demographic and clinical factors (age, plasma HIV RNA level, current and nadir CD4 counts, duration of infection, central nervous system [CNS] penetration of antiretroviral regimen) along with their interactions were entered into a regression model selection algorithm to determine the final models that best described regional brain volumes. Relative to NA, individuals with ADC exhibited decreased total gray matter and parietal cortex volumes and increased total ventricular volumes. Final regression models showed overall cerebral volume, including gray and white matter volume and volumes of the parietal, temporal, and frontal lobes and the hippocampus, were most strongly associated with disease history factors (nadir CD4 and duration of infection). In contrast, basal ganglia volumes were related most strongly to current disease factors, most notably plasma HIV RNA. These findings indicate that individuals with a history of chronic HIV infection with previous episodes of severely impaired immune function, as reflected by reduced nadir CD4+ lymphocyte count, may be at greatest risk for cerebral atrophy. The pattern of HIV-associated brain loss may be changing from a subcortical to a cortical disease among patients who are largely asymptomatic on HAART.

Keywords

CD4 nadir cortical volume duration of infection HAART HIV subcortical volume viral load 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Akaike H (1974). A new look at the statistical model identification. IEEE Trans Autom Control 19: 716–723.CrossRefGoogle Scholar
  2. Alemán-Gómez Y. Melie-García L, Valdés-Hernández P. IBASPM: Toolbox for automatic parcellation of brain structures. In: Presented at the 12th Annual Meeting of the Organization for Human Brain Mapping. Florence, Italy: Available on CD-Rom in NeuroImage. June 11–15, 2006, Vol. 27, No.1.Google Scholar
  3. Ances BM, Roc AC, Wang J, Korczykowski M, Okawa J, Stern J, Kim J, Wolf R, Lawler K, Kolson DL, Detre JA (2006). Caudate blood flow and volume are reduced in HIV+ neurocognitively impaired patients. Neurology 66: 862–866.PubMedCrossRefGoogle Scholar
  4. Aylward EH, Brettschneider PD, McArthur JC, Harris GJ, Schlaepfer TE, Henderer JD, Barta PE, Tien AY, Pearlson GD (1995). Magnetic resonance imaging measurement of gray matter volume reductions in HIV dementia. Am J Psychiatry 152: 987–994.PubMedGoogle Scholar
  5. Aylward EH, Henderer JD, McArthur JC, Brettschneider PD, Harris GJ, Barta PE, Pearlson GD (1993). Reduced basal ganglia volume in HIV-1-associated dementia: results from quantitative neuroimaging. Neurology 43: 2099–2104.PubMedGoogle Scholar
  6. Brew BJ (2004). Evidence for a change in AIDS dementia complex in the era of highly active antiretroviral therapy and the possibility of new forms of AIDS dementia complex. AIDS 18(Suppl 1): S75-S78.PubMedGoogle Scholar
  7. Brew BJ, Crowe SM, Landay A, Cysique LA, Guillemin G (2008). Neurodegeneration and Ageing in the HAART Era. J Neuroimmune Pharmacol. 4: 163–174.PubMedCrossRefGoogle Scholar
  8. Burnham K, Anderson DR (2002). Model selection and multimodel inference: a practical-theoretic approach, 2nd ed. New York: Springer-Verlag.Google Scholar
  9. Carpenter CC, Cooper DA, Fischl MA, Gatell JM, Gazzard BG, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Saag MS, Schechter M, Schooley RT, Thompson MA, Vella S, Yeni PG, Volberding PA (2000). Antiretroviral therapy in adults: updated recommendations of the International AIDS Society—USA Panel. JAMA 283: 381–390.PubMedCrossRefGoogle Scholar
  10. Chang L, Tomasi D, Yakupov R, Lozar C, Arnold S, Caparelli E, Ernst T (2004). Adaptation of the attention network in human immunodeficiency virus brain injury. Ann Neurol 56: 259–272.PubMedCrossRefGoogle Scholar
  11. Dore G, Correll P, Li Y, Kaldor J, Cooper D, Brew B (1999). Changes to AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 13: 1249–1253.PubMedCrossRefGoogle Scholar
  12. Gongvatana A, Schweinsburg BC, Taylor MJ, Theilmann RJ, Letendre SL, Alhassoon OM, Jacobus J, Woods SP, Jernigan TL, Ellis RJ, Frank LR, Grant I (2009). White matter tract injury and cognitive impairment in human immunodeficiency virus-infected individuals. J NeuroVirol 15: 187–195.PubMedCrossRefGoogle Scholar
  13. Heindel WC, Jernigan TL, Archibald SL, Achim CL, Masliah E, Wiley CA (1994). The relationship of quantitative brain magnetic resonance imaging measures to neuropathologic indexes of human immunodeficiency virus infection. Arch Neurol 51: 1129–1135.PubMedCrossRefGoogle Scholar
  14. Jernigan TL, Archibald S, Hesselink JR, Atkinson JH, Velin RA, McCutchan JA, Chandler J, Grant I (1993). Magnetic resonance imaging morphometric analysis of cerebral volume loss in human immunodeficiency virus infection. The HNRC Group. Arch Neurol 50: 250–255.PubMedCrossRefGoogle Scholar
  15. Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, Gelman BB, McArthur JC, McCutchan JA, Morgello S, Simpson D, Grant I, Ellis RJ (2008). Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 65: 65–70.PubMedCrossRefGoogle Scholar
  16. Marder K, Albert SM, McDermott MP, McArthur JC, Schifitto G, Selnes OA, Sacktor N, Stern Y, Palumbo D, Kieburtz K, Cohen B, Orme C, Epstein LG (2003). Interrater reliability of a clinical staging of HIV-associated cognitive impairment. Neurology 60: 1467–1473.PubMedGoogle Scholar
  17. Masliah E, DeTeresa RM, Mallory ME, Hansen LA (2000). Changes in pathological findings at autopsy in AIDS cases for the last 15 years. AIDS 14: 69–74.PubMedCrossRefGoogle Scholar
  18. McArthur JC (2004). HIV dementia: an evolving disease. J Neuroimmunol 157: 3–10.PubMedCrossRefGoogle Scholar
  19. Patel SH, Inglese M, Glosser G, Kolson DL, Grossman RI, Gonen O (2003). Whole-brain N-acetylaspartate level and cognitive performance in HIV infection. AJNR Am J Neuroradiol 24: 1587–1591.PubMedGoogle Scholar
  20. Patel SH, Kolson DL, Glosser G, Matozzo I, Ge Y, Babb JS, Mannon LJ, Grossman RI (2002). Correlation between percentage of brain parenchymal volume and neurocognitive performance in HIV-infected patients. AJNR Am J Neuroradiol 23: 543–549.PubMedGoogle Scholar
  21. Paul R, Cohen R, Navia B (2002). Neuroimaging relationships to cognition in patients with HIV. Neurosci Biobehav Rev 26: 353–359.PubMedCrossRefGoogle Scholar
  22. Paul RH, Ernst T, Brickman AM, Yiannoutsos CT, Tate DF, Cohen RA, Navia BA (2008). Relative sensitivity of magnetic resonance spectroscopy and quantitative magnetic resonance imaging to cognitive function among nondemented individuals infected with HIV. J Int Neuropsychol Soc 14: 725–733.PubMedCrossRefGoogle Scholar
  23. Paul RH, Yiannoutsos CT, Miller EN, Chang L, Marra CM, Schifitto G, Ernst T, Singer E, Richards T, Jarvik GJ, Price R, Meyerhoff DJ, Kolson D, Ellis RJ, Gonzalez G, Lenkinski RE, Cohen RA, Navia BA (2007). Proton MRS and neuropsychological correlates in AIDS dementia complex: evidence of subcortical specificity. J Neuropsychiatry Clin Neurosci 19: 283–292.PubMedCrossRefGoogle Scholar
  24. Sacktor N, McDermott MP, Marder K, Schifitto G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo D, Kieburtz K, De Marcaida JA, Cohen B, Epstein L (2002). HIV-associated cognitive impairment before and after the advent of combination therapy. J NeuroVirol 8: 136–142.PubMedCrossRefGoogle Scholar
  25. Thompson PM, Dutton RA, Hayashi KM, Toga AW, Lopez OL, Aizenstein HJ, Becker JT (2005). Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proc Natl Acad Sci USA 102: 15647–15652.PubMedCrossRefGoogle Scholar
  26. Thurnher MM, Schindler EG, Thurnher SA, Pernerstorfer-Schon H, Kleibl-Popov C, Rieger A (2000). Highly active antiretroviral therapy for patients with AIDS dementia complex: effect on MR imaging findings and clinical course. AJNR Am J Neuroradiol 21: 670–678.PubMedGoogle Scholar
  27. Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, Mazoyer B, Joliot M (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15: 273–289.PubMedCrossRefGoogle Scholar
  28. Valcour V, Sacktor N (2002). HIV-associated dementia and aging. J Ment Health Aging 8: 295–306.Google Scholar
  29. Valcour V, Shikuma C, Waters M, Sacktor N (2004). Cognitive impairment in older HIV-1 seropositive individuals: prevalence and potential mechanisms. AIDS 18(Suppl 1): S79-S86.PubMedGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2010

Authors and Affiliations

  • Ronald A. Cohen
    • 1
    Email author
  • Jaroslaw Harezlak
    • 2
  • Giovanni Schifitto
    • 3
  • George Hana
    • 1
  • Uraina Clark
    • 1
  • Assawin Gongvatana
    • 1
  • Robert Paul
    • 4
  • Michael Taylor
    • 5
  • Paul Thompson
    • 6
  • Jeffery Alger
    • 6
  • Mark Brown
    • 7
  • Jianhui Zhong
    • 3
  • Thomas Campbell
    • 7
  • Elyse Singer
    • 6
  • Eric Daar
    • 8
  • Deborah McMahon
    • 9
  • Yuen Tso
    • 10
  • Constantin T. Yiannoutsos
    • 2
  • Bradford Navia
    • 11
    • 12
    Email author
  • HIV Neuroimaging Consortium
  1. 1.Department of Psychiatry and Human Behavior and the Brain Science ProgramBrown University School of MedicineProvidenceUSA
  2. 2.Department of MedicineIndiana University School of MedicineIndianapolisUSA
  3. 3.Department of NeurologyRochester School of MedicineRochesterUSA
  4. 4.Department of PsychologyUniversity of MissouriSt. LouisUSA
  5. 5.Department of PsychiatryUniversity of California-San DiegoLa JollaUSA
  6. 6.Departments of Neurology and Radiological ScienceUniversity of CaliforniaLos Angeles, WestwoodUSA
  7. 7.Departments of Psychiatry and Internal MedicineUniversity of Colorado-DenverAuroraUSA
  8. 8.Department of MedicineHarbor-UCLA Medical CenterLos AngelesUSA
  9. 9.Department of NeurologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  10. 10.Department of NeurologyStanford University School of MedicinePalo AltoUSA
  11. 11.Department of Public Health and Community MedicineTufts University School of MedicineBoston
  12. 12.Department of NeurologyTufts University School of MedicineBostonUSA

Personalised recommendations