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.

Macrophages in Progressive Human Immunodeficiency Virus/Simian Immunodeficiency Virus Infections

“…More severe disease can include HIV-associated encephalitis (33). While there are conflicting reports on potential effects of HIV-1 clade type on HAD incidence, HIV clade type may influence the likelihood that persons living with HIV will develop neurocognitive disorders and/or the severity of HAD onset and progression (34). For example, HIV-1 clade D virus is associated with a higher frequency of HAD than HIV-1 clade C (34).…”

“…With the advent of highly active antiretroviral therapy (HAART), the severity of HAD has significantly decreased (34,52,53). However, subtler neurological disorders can arise even in individuals who are aviremic with HAART (54).…”

“…These milder neurological disorders have been collectively designated HIV-associated neurocognitive disorder (HAND). Though the frequency of HAD has significantly decreased with HAART, approximately half of all HIV-infected individuals develop some form of HAND (34,55,56). One plausible explanation for HAND is decreased, but incompletely suppressed, viral replication within the central nervous system (CNS) (54,57).…”

Evaluation of practice effect on neuropsychological measures among persons with and without HIV infection in northern India

“…HIV-1 infection in Western countries, however, primarily results from clade B virus (Gannon et al, 2011), while in India it primarily results from clade C (Robertson et al, 2010). Since there are differences in the structures of clade B and C virus that can affect each clade’s neurotropism and neurovirulence (Tyor et al, 2013), it is not clear that research on neuropsychological performance of affected individual in the West can be validly generalized to persons in India. This is especially important given findings that HIV-1 infection in India is associated with neurocognitive deficits.…”

“…These studies, however, are limited and their results have been inconsistent (Gupta et al, 2007; Yepthomi et al, 2006). Other researchers (Tyor et al, 2013) have argued that ascertainment of cognitive impairment in India may be biased due to participant selection methods and the lack of adequate normative data for diverse groups and languages (Waldrop-Valverde et al, 2015). …”