Abstract
Neurocognitive impairments associated with human immunodeficiency virus (HIV) infection remain a considerable health issue for almost half the people living with HIV, despite progress in HIV treatment through combination antiretroviral therapy (cART). The pathogenesis and risk factors of HIV-associated neurocognitive disorder (HAND) are still incompletely understood. This is partly due to the complexity of HAND diagnostics, as phenotypes present with high variability and change over time. Our current understanding is that HIV enters the central nervous system (CNS) during infection, persisting and replicating in resident immune and supporting cells, with the subsequent host immune response and inflammation likely adding to the development of HAND. Differences in host (human) genetics determine, in part, the effectiveness of the immune response and other factors that increase the vulnerability to HAND. This review describes findings from studies investigating the role of human host genetics in the pathogenesis of HAND, including potential risk factors for developing HAND. The similarities and differences between HAND and Alzheimer’s disease are also discussed. While some specific variations in host genes regulating immune responses and neurotransmission have been associated with protection or risk of HAND development, the effects are generally small and findings poorly replicated. Nevertheless, a few specific gene variants appear to affect the risk for developing HAND and aid our understanding of HAND pathogenesis.
Highlights
The human immunodeficiency virus (HIV) epidemic is a huge public health issue worldwide, and is prominent in developing countries
In the central nervous system (CNS), HIV-infected microglia and macrophages secrete a large amount of chemokines/cytokines that cause apoptosis, degeneration of the blood-brain barrier (BBB), and glutamate reuptake; chronic inflammation is important in the progression of HIV-associated neurocognitive disorder (HAND)
HIV entry involves an initial interaction between gp120 and the host CD4 receptor, following which gp120 binds to the CCR5 co-receptor on the host cell
Summary
The human immunodeficiency virus (HIV) epidemic is a huge public health issue worldwide, and is prominent in developing countries. HAND is currently sub-classified into three forms, according to the Frascati criteria [16]: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) and HIV-associated dementia (HAD) (Figure 1) This criteria has been adapted by other countries on the African continent, such as South Africa [4]. The prevalence in developing countries like South Africa is similar, with a wide range from 15 to 60%, depending on the setting [4,5,24,25] The causes of these cognitive impairments are likely to be multifactorial, and include factors such as cardiovascular and metabolic effects, drug use and depression [27]. While there is biological plausibility in using ARVs with greater CNS penetration to treat HAND, the effectiveness of this approach is still unclear and other types of intervention are required
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