Global HIV neurology

Abstract

: Neurological conditions associated with HIV remain major contributors to morbidity and mortality and are increasingly recognized in the aging population on long-standing combination antiretroviral therapy (cART). Importantly, growing evidence shows that the CNS may serve as a reservoir for viral replication, which has major implications for HIV eradication strategies. Though there has been major progress in the last decade in our understanding of the pathogenesis, burden, and impact of neurological conditions associated with HIV infection, significant scientific gaps remain. In many resource-limited settings, ARVs considered second or third line in the United States, which carry substantial neurotoxicity, remain mainstays of treatment, and patients continue to present with severe immunosuppression and central nervous system (CNS) opportunistic infections. Despite this, increased global access to cART has coincided with an aging HIV+ population with cognitive sequelae, cerebrovascular disease, and peripheral neuropathy. Further neurological research in low-income and middle-income countries (LMICs) is needed to address the burden of neurological complications in HIV+ patients, particularly regarding CNS viral reservoirs and their effects on eradication.

The Brain Retains: Nonhuman Primate Models for Pediatric HIV-1 in the CNS

“…Even with ART, HAND is associated with greater risk for disease progression and poorer morbidity [6]. It is estimated that up to 50% of ART-treated children will develop neurologic complications [7][8][9][10][11]. Clinical manifestations include mild to severe neurocognitive impairment, delays in motor development, and behavioral psychiatric conditions such as depression and attention-deficit hyperactivity disorder (ADHD).…”

HIV Neuroinfection and Alzheimer’s Disease: Similarities and Potential Links?

“…Nonetheless, the virus can access the brain very early on during primary infection (within the first 2 weeks) where it can locally replicate and become compartmentalized, as determined by recent phylogenetic analyses (Sturdevant et al, 2015 ). The virus then leads to neurotoxicity that is associated with motor, sensory and cognitive impairment in around 50% of HIV + patients (Becker et al, 2009 ; Thakur et al, 2018 ). These neuronal impairments are collectively named HAND (González-Scarano and Martín-García, 2005 ; Clifford and Ances, 2013 ; Thakur et al, 2018 ).…”

“…The virus then leads to neurotoxicity that is associated with motor, sensory and cognitive impairment in around 50% of HIV + patients (Becker et al, 2009 ; Thakur et al, 2018 ). These neuronal impairments are collectively named HAND (González-Scarano and Martín-García, 2005 ; Clifford and Ances, 2013 ; Thakur et al, 2018 ). Depending on the severity of the symptoms, these conditions are classified into three groups: asymptomatic neurocognitive impairment (ANI), mild neurocognitive disorder (MND) and HIV-associated dementia (HAD) (Antinori et al, 2007 ).…”

“…In the post-cART era, the total proportion of patients with HAND did not vary but the distribution of the classes changed with a decrease in HAD and an increase in MND and ANI (González-Scarano and Martín-García, 2005 ). Moreover, neuronal disorders are becoming more frequent in the aging HIV + population (Thakur et al, 2018 ). Prospective trials have found poor prediction on the effect of cART on the patient’s cognitive impairment as the BBB limits the penetration of the drugs into the brain and some antiretrovirals (ARV) can show neurotoxicity (Soontornniyomkij et al, 2018 ; Thakur et al, 2018 ).…”

“…Moreover, neuronal disorders are becoming more frequent in the aging HIV + population (Thakur et al, 2018 ). Prospective trials have found poor prediction on the effect of cART on the patient’s cognitive impairment as the BBB limits the penetration of the drugs into the brain and some antiretrovirals (ARV) can show neurotoxicity (Soontornniyomkij et al, 2018 ; Thakur et al, 2018 ). In this context, HAD has also been proposed as the most common form of dementia in people under 40 years of age (Janssen, 1992 ).…”