HIV-associated neuropathogenesis: A systems biology perspective for modeling and therapy

Abstract

Despite the development of powerful antiretroviral drugs, HIV-1 associated neurological disorders (HAND) will affect approximately half of those infected with HIV-1. Combined anti-retroviral therapy (cART) targets viral replication and increases T-cell counts, but it does not always control macrophage polarization, brain infection or inflammation. Moreover, it remains difficult to identify those at risk for HAND. New therapies that focus on modulating host immune response by making use of biological pathways could prove to be more effective than cART for the treatment of neuroAIDS. Additionally, while numerous HAND biomarkers have been suggested, they are of little use without methods for appropriate data integration and a systems-level interpretation. Machine learning, could be used to develop multifactorial computational models that provide clinicians and researchers with the ability to identify which factors (in what combination and relative importance) are considered important to outcome.

HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads

“…Because persistent macrophage activation is associated with an inhibition of apoptosis, HIV ϩ macrophages likely have a survival advantage, acting as a continuous source of HIV and serving as a long-term site of viral persistence or viral rebound after cART discontinuation (97). Considering the wide range of macrophage-associated diseases (atherosclerosis, cancer, neurological disease) seen in this particular cohort, therapeutics that target subsets of activated macrophages (98-100) or their associated disease processes by altering host biological pathways is an interesting approach for controlling HIV-associated morbidities and has potential for impacting the brain compartment independent of pVL measurements (101). Additionally, the study raises important questions: Is tissue pathogenesis during HIV infection entirely independent of pVL?…”

Why do Young Adults Living With Hiv Perform Poorly On Combined Antiretroviral Therapy (CART)? – a Zimbabwean Perspective

“…Additionally, monocytes that migrate from the periphery can carry the virus into the brain [22]. Once in the brain tissue, monocytes transform to become macrophage and phagocytosis by macrophages results in increased virus accumulation in the macrophages and the brain [23]. Once resident in the brain, the virus enter the astrocytes some of whom express the chemokine CCR5 and also the virus enters the astrocytes through cell-to-cell contact [24,25].…”

Relevance of retrovirus quantification in cerebrospinal fluid for neurologic diagnosis

“…However, milder forms of HIV-associated neurologic disorders became highly prevalent. Thus, a new denomination was suggested: HIV-associated neurocognitive disorders (HAND) [ 7 , 27 ]. According to this new terminology, HAND can be further classified into asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD).…”

“…According to this new terminology, HAND can be further classified into asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND), and HIV-associated dementia (HAD). HAND is estimated to affect up to 50 % of HIV-infected individuals [ 7 , 27 ]. It is important to note that the prevalence of HAD decreased in the cART era, but for mild to moderate HAND forms.…”

“…The determination of the HIV viral load in blood is widely used to assess the disease progression and the response to antiretroviral therapy. As previously mentioned, HIV can infect the CNS, and HAND can be observed even in patients with adequate control of viral replication in plasma [ 7 – 9 , 18 , 22 , 39 ]. The mechanism that leads to the persistence of neurologic impairment in patients with suppressed viral replication in the bloodstream is poorly understood.…”