This article has emphasized on the non-AIDS conditioned HIV-associated neurocognitive impairment (HAND), an umbrella term that refers to deficiencies in memory, concentration, attention and motor skills in individuals with HIV.
Apart from neuropsychological testing, HAND requires Cerebro-spinal fluid (CSF) biomarkers (such as elevated Neopterin, high leveled neurofilament light chain (NFL), breakdown of BBB marker etc) recognition test. It has been seen that both Neopterin and NFL are elevated in participants with mild neurocognitive disorder (MND) and the asymptomatic neurocognitive impairment (ANI).
During acute infection associated with immune cell trafficking, HIV enters the central nervous system (CNS) and evolves independently into a compartmentalized CNS virus. This CNS HIV is more typically macrophage tropic, allowing it to persist in CNS perivascular macrophages and monocytes despite predictably low levels of CD4+ T cells in this environment. Infected CNS undergoes neuronal injury due to inflammatory cytokines and neurotoxins released by macrophage and microglial cells. Untreated patients with chronic infection show one tenth HIV infection in the plasma. It can be controlled by preventing HIV infection in the peripheral blood. Viral RNA can be detected in the CSF by the sensitivity of the detection assay, termed as “CNS escape” and the plasma viral suppression. However, autopsy studies revealed that HIV DNA is present in the brain even during systematically suppressive combined antiretroviral therapy (cART).
Chronic HIV depletes the naïve T cells and increases the proportion of memory T cells and activated T cells in the CSF as well as in the blood. HIV patients with severe neurocognitive impairment show the highest rate of activated T cells in the CSF. Additionally, compared to uninfected individuals, infected patients show a lower CSF CD4+:CD8+ ratio which in turn is associated with worsened neurocognitive impairment.
It has been reported that older individuals with non-AIDS HIV disease are at higher risk for renal disease, certain malignancies, cardiovascular disease and neurocognitive impairment than general populations. A study by Goodkin and colleagues suggests that aging accelerates HIV’s deleterious effects on the specific neurocognitive domains of episodic memory and motor function.
When it comes to pediatric HIV, neurological manifestations include cerebrovascular disease, epileptic seizures, and cognitive issues. Cognitive impairment in children with HIV is broad, usually encompassing multiple domains and more severe in children with a history of AIDS-defining illness.
Early cART plays a role in preventing neuro-HIV disease in participants who are cognitively normal at baseline. The cART improves cognitive performance in antiretroviral naïve patients with established HAND. In addition, the drugs that were most frequently used in the high- CNS penetration-effectiveness (CPE) group were emtricitabine, zidovudine and lopinavir etc. Furthermore, two drugs named cenicriviroc and natalizumab offer hope in blockade of cellular trafficking which may lead to improvements in HAND. Recent studies have shed further light on the potential to treat and prevent HAND using cART and have elucidated immune mechanisms that contribute to HAND and which may form the basis for further targeted therapy.
Reference:
Farhadian, S., Patel, P. & Spudich, S. Neurological Complications of HIV Infection. Curr Infect Dis Rep19, 50 (2017). https://doi.org/10.1007/s11908-017-0606-5
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