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Cliniconeuropathologic correlates of human immunodeficiency virus in the era of antiretroviral therapy |
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| Authors: | I Everall F Vaida N Khanlou D Lazzaretto C Achim S Letendre D Moore R Ellis M Cherner B Gelman S Morgello E Singer I Grant E Masliah |
| Institution: | 1. HIV Neurobehavioral Research Center (HNRC), University of California, San Diego, La Jolla, California, USA 2. Department of Psychiatry, University of California, San Diego, 9500 Gilman Drive, 92093-0603, La Jolla, CA, USA 3. Department of Medicine, University of California, San Diego, La Jolla, California, USA 4. Department of Neuroscience, University of California, San Diego, La Jolla, California, USA 5. Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA 6. Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Texas, USA 7. Department of Pathology, Mount Sinai Medical Center, New York, USA 8. Department of Neuroscience, Mount Sinai Medical Center, New York, USA 9. Department of Neurology, University of California, Los Angeles, California, USA |
| Abstract: | The objective of this study was to examine the spectrum of human immunodeficiency virus (HIV) brain pathology and its clinical correlates in the antiretroviral era. We carried out a cross-sectional survey, analyzing prospective clinical and neuropathological data collected by the National NeuroAIDS Tissue Consortium (NNTC), comprising 589 brain samples from individuals with advanced HIV disease collected from 1999 onwards. We assessed gender, ethnicity/race, mode of transmission, age, year of death, nadir CD4, plasma viral load, last antiretroviral regimen, presence of parenchymal HIV brain pathology, HIV-associated neurocognitive disorder, and major depressive disorder. We compared cohort demographic variables with Centers for Disease Control and Prevention US HIV/AIDS statistics and examined associations of parenchymal HIV brain pathology with demographic, clinical, and HIV disease factors. With regard to Centers for Disease Control and Prevention US data, the NNTC was similar in age distribution, but had fewer females and African Americans and more Hispanics and men who have sex with men. Only 22% of the brains examined were neuropathologically normal. Opportunistic infections occurred in 1% to 5% of the cohort. Parenchymal HIV brain pathology was observed in 17.5% of the cohort and was associated with nadir CD4 and plasma viral load. Brains without parenchymal HIV brain pathology often had other noninfectious findings or minimal nondiagnostic abnormalities that were associated with HIV-associated neurocognitive disorder. Clinically, 60% of the cohort reported a lifetime episode of major depressive disorder and 88% had a HIV-associated neurocognitive disorder. No pathological finding correlated with major depressive disorder. Both antiretroviral treatment regimen and elevated plasma HIV viral load were associated with presence of parenchymal HIV brain pathology; however, multivariate analyses suggest a stronger association with plasma viral load. The frequency of HIV brain pathology was lower than previous pre-antiretroviral reports, and was predicted by lower nadir CD4 and higher plasma viral load. Noninfectious pathologies and minimal changes correlated with HIV-associated neurocognitive disorder, suggesting a shift in pathogenesis from florid HIV replication to other, diverse mechanisms. |
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