title: Effect of HIV clade differences on the onset and severity of HIV-associated neurocognitive disorders.
abstract: The effects of evolutionary pressure on human immunodeficiency virus-1 (HIV) have resulted in a variety of clades and recombinants. The functional implications of HIV clades on disease onset and progression of HIV-associated neurocognitive disorders (HAND) have been suggested by clinical and basic science studies, which will be reviewed in detail. Some clinical studies suggest that patients infected with clade D show the greatest propensity for developing HIV-associated dementia (HAD) followed by clades B, C, and A, respectively. However, there are conflicting reports. This review summarizes clinical studies that have assessed behavioral abnormalities and HIV clade type in HAND patients, focusing on the clades stated above. The limitations include variations in testing used to define the cohorts, patient sample size, lack of HIV clade characterization, combination antiretroviral therapy (cART) availability, and other factors, which are highlighted and compared between clinical studies performed primarily in Africa and India. Basic science studies provide substantial evidence that HIV clade differences can result in varying degrees of neuropathology and are also reviewed in some detail. These studies indicate that there are a number of clade differences, most notably in Tat, that result in different degrees of neurovirulence or neuropathological effects in vitro and in a mouse model of HAND. In order to confirm the hypothesis that HIV clade differences are important determinants of HAND pathogenesis, larger, longitudinal studies that employ standard definitions of HAND and HIV clade testing must be performed. In a larger sense, HAND continues to be highly prevalent despite the advent of cART, and therefore, further studies into HAND pathogenesis are critical to develop better therapies.
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, GA, USA, william.tyor@va.gov.
authors.forename: William
authors.initials: W
authors.lastname: Tyor
authors.forename: Cari
authors.initials: C
authors.lastname: Fritz-French
authors.forename: Avindra
authors.initials: A
authors.lastname: Nath
mesh_terms: D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000503:physiopathology* / Q000821:virology; D017668:Age of Onset; D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D051379:Mice; D009483:Neuropsychological Tests; D018579:Patient Selection; D018401:Sample Size; D012720:Severity of Illness Index
chemical_list: D019380:Anti-HIV Agents