Abstract
Human immunodeficiency virus type 1 (HIV-1) tropism plays an important role in HIV-associated dementia. In this study, aimed at determining if the tropism and coreceptor usage of circulating viruses correlates with cognitive function, the authors isolated and characterized HIV from the peripheral blood of 21 Hispanic women using antiretroviral therapy. Macrophage tropism was determined by inoculation of HIV isolates onto monocyte-derived macrophages and lymphocyte cultures. To define coreceptor usage, the HIV isolates were inoculated onto the U87.CD4 glioma cell lines with specific CCR5 and CXCR4 coreceptors. HIV isolates from cognitively impaired patients showed higher levels of replication in mitogen-stimulated peripheral blood mononuclear cells than did isolates from patients with normal cognition (P < .05). The viral growth of HIV primary isolates in macrophages and lymphocytes did not differ between patients with and those without cognitive impairment. However, isolates from the cognitively impaired women preferentially used the X4 coreceptor (P < .05). These phenotypic studies suggest that cognitively impaired HIV-infected women receiving treatment may have a more highly replicating and more pathogenic X4 virus in the circulation that could contribute to their neuropathogenesis.
The authors thank their patients for supporting this research. Tania Ginebra and Tania de la Torre provided patient outreach, and Dr. Rosa Hechavarría performed neuropsychological testing. The authors thank Drs. Carmen Zorrilla and Hermes García (clinic directors) for referring patients; the RCMI-Clinical Research Center for providing staff and supplies for laboratory sample collections; and Dr. Howard Gendelman for providing elutriated monocytes for studies of macrophage tropism. The authors acknowledge the Swartz Foundation for support of part of this work. Dr. Edmundo Kraiselburd's continuous support for this project and the Puerto Rico Specialized Neuroscience Program in NeuroAIDS in general are greatly appreciated. The authors are grateful to the NIH AIDS Research and Reference Reagent Program for providing the MT-2 cells, U87.CD4.CCR5/U87.CD4.CXCR4 cell lines, HIV-BAL and HIV-LAI viral isolates. This work was supported by the following grants: NIH-SNRP 1 U54NS430, NIH-MBRS-SCORE-SO6GMO822, NIH-RCMI-CRC P20RR11126, and GM61838 from the MBRS-RISE Program.