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High level HIV-1 DNA concentrations in brain tissues differentiate patients with post-HAART AIDS dementia complex or cardiovascular disease from those with AIDS

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Abstract

Highly active antiretroviral treatment (HAART) has had a significant impact on survival of individuals with acquired immunodeficiency syndrome (AIDS); however, with the longer life-span of patients with AIDS, there is increasing prevalence of AIDS dementia complex (ADC) and other non-AIDS-defining illness, and cardiovascular diseases (CVD) are also common. The influence of these varied disease processes on HIV-1 DNA concentration in brain tissues has not been thoroughly assessed in the post-HAART era. The purpose of the current study is to clarify the impacts of ADC and other complications of HIV disease on the viral load in the brains in AIDS patients with post-HARRT. We examined autopsy specimens from the brains of thirteen patients who died from complications of AIDS with quantitative polymerase chain reaction (QPCR). All but one patient had received HAART prior to death since 1995. Two patients died with severe CVD, multiple cerebrovascular atherosclerosis (CVA) throughout the brain and five patients died with ADC. Six patients had no ADC/CVA. A QPCR was used to measure the presence of HIV-1 DNA in six brain tissues (meninges, frontal grey matter, frontal white matter, temporal subcortex, cerebellum and basal ganglia). In the post-HARRT era, for non-ADC/CVA patients, HIV-1 DNA concentration in brain tissues was statistically higher than that in patients with ADC. In a new finding, two patients who suffered from severe CVD, especially CVA, also had high concentrations of HIV-1 in brain compartments not showing ADC related changes. To our knowledge, this is the first report of a relationship between the CVA and HIV-1 viral burden in brain. The current observations suggest that HAART-resistant HIV reservoirs may survive within ADC lesions of the brain as well as the macrophage rich atherosclerosis, which needs to be confirmed by more AIDS cases with CVA.

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References

  1. Gonzalez-Scarano F, Martin-Garcia J. The neuropathogenesis of AIDS. Nat Rev Immunol, 2005, 5: 69–81, 15630430, 10.1038/nri1527, 1:CAS:528:DC%2BD2MXlvVOn

    Article  PubMed  CAS  Google Scholar 

  2. Sacktor N. The epidemiology of human immunodeficiency virus-associated neurological disease in the era of highly active antiretroviral therapy. J Neurovirol, 2002, 8(suppl 2): 115–121, 12491162, 10.1080/13550280290101094, 1:CAS:528:DC%2BD3sXht1Sitbg%3D

    Article  PubMed  CAS  Google Scholar 

  3. Sacktor N, Lyles R H, Skolasky R, et al. HIV-associated neurologic disease incidence changes: Multicenter AIDS Cohort Study, 1990–1998. Neurology, 2001, 56: 257–260, 11160967, 1:STN:280:DC%2BD3M7pt1yhuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  4. Sacktor N, Tarwater P M, Skolasky R L, et al. CSF antiretroviral drug penetrance and the treatment of HIV-associated psychomotor slowing. Neurology, 2001, 57: 542–544, 11502933, 1:STN:280:DC%2BD3MvmvVSisQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  5. Palella F J Jr, Baker R K, Moorman A C, et al. Mortality in the highly active antiretroviral therapy era changing cause of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr, 2006, 43: 27–34, 16878047, 10.1097/01.qai.0000233310.90484.16, 1:CAS:528:DC%2BD28XosFGmtro%3D

    Article  PubMed  CAS  Google Scholar 

  6. Bozzette S A, Ake C F, Tam H K, et al. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med, 2003, 348: 702–710, 12594314, 10.1056/NEJMoa022048, 1:CAS:528:DC%2BD3sXhtlWjt7Y%3D

    Article  PubMed  CAS  Google Scholar 

  7. Friis-Mıller N, Sabin C A, Weber R, et al. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med, 2003, 349: 1993–2003, 10.1056/NEJMoa030218

    Article  Google Scholar 

  8. Holmberg S D, Moorman A C, Williamson J M, et al. Protease inhibitors and cardiovascular outcomes in patients with HIV-1. Lancet, 2002, 360: 1747–1748, 12480430, 10.1016/S0140-6736(02)11672-2, 1:CAS:528:DC%2BD38Xpt12msLg%3D

    Article  PubMed  CAS  Google Scholar 

  9. Mooser V. Atherosclerosis and HIV in the highly active antiretroviral therapy era: toward an epidemic of cardiovasvular disease? AIDS, 2003, 17(suppl 1): s65–s69, 12870532

    Article  PubMed  Google Scholar 

  10. Sudano I, Spieker L E, Noll G, et al. Cardiovascular disease in HIV infection. Am Heart J, 2006, 151: 1147–1155, 16781213, 10.1016/j.ahj.2005.07.030

    Article  PubMed  Google Scholar 

  11. Stein J H, Klein M A, Bellehumeur J L, et al. Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction. Circulation, 2001, 104: 257–262, 11457741, 1:CAS:528:DC%2BD3MXlslOmt7k%3D

    Article  PubMed  CAS  Google Scholar 

  12. Monier P, McKown K, Bronze M S. Osteonecrosis complicating highly active antiretroviral therapy in patients infected with human immunodeficiency virus. Clin Infect Dis, 2000, 31: 1488–1492, 11096017, 10.1086/317503, 1:STN:280:DC%2BD3M3isVSnsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  13. Meng Q, Lima J A, Lai H, et al. Coronary artery calcification, atherogenic lipid changes, and increased erythrocyte volume in black injection drug users infected with human immunodeficiency virus-1 treated with protease inhibitors. Am Heart J, 2002 144: 642–648, 12360160

    Article  PubMed  Google Scholar 

  14. Hsue P Y, Lo J C, Franklin A, et al. Progression of atherosclerosis as assessed by carotid intima-media thickness in patients with HIV infection. Circulation, 2004, 109: 1603–1608, 15023877, 10.1161/01.CIR.0000124480.32233.8A

    Article  PubMed  Google Scholar 

  15. Shah S S, Zimmerman R A, Rorke L B, et al. Cerebrovascular complications of HIV in children. Am J Neuroradiol, 1996, 17: 1913–1917, 8933877, 1:STN:280:DyaK2s%2Fosl2gug%3D%3D

    PubMed  CAS  Google Scholar 

  16. An S F, Groves M, Giometto B, et al. Detection and localisation of HIV-1 DNA and RNA in fixed adults AIDS brain by polymerase chain reaction/in situ hybridisation technique. Acta Neuropathol, 1999, 98: 481–487, 10541871, 10.1007/s004010051113, 1:CAS:528:DyaK1MXmtFOjtbc%3D

    Article  PubMed  CAS  Google Scholar 

  17. Bell J E, Brettle R P, Chiswick A, et al. HIV encepholitis, proviral load and dementia in drug users and homosexuals with AIDS Effect of neocortical involvement. Brain, 1998, 121(Pt11): 2043–2052, 9827765, 10.1093/brain/121.11.2043

    Article  PubMed  Google Scholar 

  18. Glass J D, Fedor H, Wesselingh S L, et al. Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia. Ann Neurol, 1995, 38: 755–762, 7486867, 10.1002/ana.410380510, 1:STN:280:DyaK28%2FnsVWrtQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  19. Johnson R T, Glass J D, McArthur J C, et al. Quantitation of Human Immunodeficiency Virus in Brains of Demented and Nondemented Patients with Acquired Immunodeficiency Syndrome. Ann Neurol, 1996, 39: 392–395, 8602761, 10.1002/ana.410390319, 1:STN:280:DyaK287otV2hsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  20. van Marle G, Power C. Human immunodeficiency virus type 1 genetic diversity in the nervous system: Evolutionary epiphenomenon or disease determinant? J Neurovirol, 2005, 11: 107–128, 16036790, 10.1080/13550280590922838, 1:CAS:528:DC%2BD2MXjvFajt78%3D

    Article  PubMed  CAS  Google Scholar 

  21. Ohagen A, Devitt A, Kunstman K J, et al. Genetic and functional analysis of full-length human immunodeficiency virus type 1 env genes derived from brain and blood of patients with AIDS. J Virol, 2003, 77: 12336–12345, 14581570, 10.1128/JVI.77.22.12336-12345.2003, 1:CAS:528:DC%2BD3sXovVantLY%3D

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Wiley C A, Achim C L, Chritopherson C, et al. HIV mediates a productive infection of the brain. AIDS, 1999, 13: 2055–2059, 10546857, 10.1097/00002030-199910220-00007, 1:CAS:528:DyaK1MXnsVSitb0%3D

    Article  PubMed  CAS  Google Scholar 

  23. Paton P, Poly H, Gonnaud P M, et al. Acute meningoradiculitis concomitant with seroconversion to human immunodeficiency virus type 1. Res Virol, 1990, 141: 427–433, 2080315, 10.1016/0923-2516(90)90043-I, 1:STN:280:DyaK3M7otVClsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  24. Salemi M, Lamers S L, Yu S, et al. Phylodynamic analysis of human immunodeficiency virus type 1 in distinct brain compartments provides a model for the neuropathogenesis of AIDS. J Virol, 2005, 79: 11343–11352, 16103186, 10.1128/JVI.79.17.11343-11352.2005, 1:CAS:528:DC%2BD2MXps1Glt7g%3D

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Hansson G K. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med, 2005, 352: 1685–1695, 15843671, 10.1056/NEJMra043430, 1:CAS:528:DC%2BD2MXjsFCltrc%3D

    Article  PubMed  CAS  Google Scholar 

  26. Linton M F, Fazio S. Macrophages, inflammation, and atherosclerosis. International Journal of Obesity, 2003, 27Suppl 3: s35–s40, 14704742, 10.1038/sj.ijo.0802498, 1:CAS:528:DC%2BD2cXls1Gk

    Article  PubMed  CAS  Google Scholar 

  27. Ross R. Cell biology of atherosclerosis. Annu Rev Physiol, 1995, 57: 791–804, 7778883, 10.1146/annurev.ph.57.030195.004043, 1:CAS:528:DyaK2MXksVeqsbY%3D

    Article  PubMed  CAS  Google Scholar 

  28. Williams K C, Hickey W F. Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS. Annu Rev Neurosci, 2002, 25: 537–562, 12052920, 10.1146/annurev.neuro.25.112701.142822, 1:CAS:528:DC%2BD38XmtF2hsbk%3D

    Article  PubMed  CAS  Google Scholar 

  29. Barbaro G. Cardiovascular manifestations of HIV Infection. Circulation, 2002, 106: 1420–1425, 12221062, 10.1161/01.CIR.0000031704.78200.59

    Article  PubMed  Google Scholar 

  30. Barbaro G, Fisher S D, Lipshultz S E. Pathogenesis of HIV-associated cardiovascular complications. Lancet Infect Dis, 2001, 1: 115–124, 11871462, 10.1016/S1473-3099(01)00067-6, 1:CAS:528:DC%2BD38XltVOntbk%3D

    Article  PubMed  CAS  Google Scholar 

  31. Currier J S, Taylor A, Boyd F, et al. Coronary heart disease in HIV-infected individuals. J Acquir Immune Defic Syndr, 2003, 33: 506–512, 12869840

    Article  PubMed  Google Scholar 

  32. Magen E, Elbirt D, Sthoeger Z. Cardiovascular disease prevention and treatment in patients with human immunodeficiency virus. Isr Med Assoc J, 2005, 7: 252–256, 15847207

    PubMed  Google Scholar 

  33. An S F, Giometto B, Scaravilli F. HIV-1 DNA in brain in AIDS and pre-AIDS: correlation with the stage of disease. Ann Neurol, 1996, 40: 611–617, 8871581, 10.1002/ana.410400411, 1:CAS:528:DyaK28XmvFWntLk%3D

    Article  PubMed  CAS  Google Scholar 

  34. Bockstahler L E, Werner T, Festl H, et al. Distribution of HIV genomic DNA in brain of AIDS patients. Clin Diagn Virol, 1995, 3: 61–72, 15566788, 10.1016/0928-0197(94)00023-N, 1:STN:280:DC%2BD2crptlCnsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  35. Williams K C, Corey S, Westmoreland SV, et al. Perivascular macrophages are the primary cell type productively infected by simian immunodeficiency virus in the brains of macaques: Implications for the neuropathogenesis of AIDS. J Exp Med, 2001, 193: 905–915, 11304551, 10.1084/jem.193.8.905, 1:CAS:528:DC%2BD3MXivFOhtr8%3D

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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Correspondence to Michael S. McGrath.

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Supported by the National Institutes of Health (Grant Nos. NIH ZMH1 BRB-S and UOI CA66259-09 TDC), National Science Foundation (Grant No. NSF DMI-0349669), abd Science & Technology Development Program of Shandong Province (Grant No. 2007GG30002003).

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Zhao, L., Galligan, D.C., Lamers, S.L. et al. High level HIV-1 DNA concentrations in brain tissues differentiate patients with post-HAART AIDS dementia complex or cardiovascular disease from those with AIDS. SCI CHINA SER C 52, 651–656 (2009). https://doi.org/10.1007/s11427-009-0085-5

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  • DOI: https://doi.org/10.1007/s11427-009-0085-5

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