HIV-Associated Neurocognitive Disorder: How HIV Affects The Brain
- devillamcn
- 23 minutes ago
- 3 min read
Introduction
HIV affects over 40 million people worldwide, with up to 77% of patients accessing antiretroviral therapy. Despite efforts to control the progression of the disease with antiretroviral therapy, approximately 30-50% of people living with HIV may develop HIV-associated neurocognitive disorder, or HAND. These patients present with difficulties in executive function, memory, attention, verbal fluency, and concentration.
Pathogenesis
HIV enters the central nervous system via infected white blood cells called monocytes and crosses the blood-brain barrier to establish infection in microglial cells (immune cells of the central nervous system). The HIV proteins gp120 and Tat are known to be neurotoxic to human brain endothelial cells. They are involved in the degradation of the blood-brain barrier while causing direct damage to neurons, microglial cells, and astrocytes. Subsequent activation of microglia is a direct response to the infection, leading to the release of inflammatory proteins and triggering an inflammatory cascade within the brain. As HIV persists in the brain, the burden of chronic neuroinflammation and oxidative stress predicts the overall progression of the disease.
Risk Factors
The risk factors for developing HAND include HIV-related factors such as low nadir CD4+ cell count <200 and lack of viral suppression. Demographic risk factors include increasing age, lower educational level, and female sex. Additionally, comorbid risk factors appreciably contribute to the development of HAND. These include hypertension, hyperlipidemia, diabetes, and co-infection with hepatitis C.
Diagnosis and Classification
The diagnosis of HAND involves neurocognitive testing with acquired impairment in at least two out of five tested domains (complex attention, executive function, learning and memory, language, perceptual-motor control, social cognition). The Montreal Cognitive Assessment exam and the Mini Mental State Exam are examples of screening tools that may be employed along with the patient’s medical history to detect HAND.
This disorder is classified into three main types based on the Frascati diagnostic criteria. These include asymptomatic neurocognitive impairment (no overt functional impairment), mild neurocognitive impairment (evidence of mild overt functional impairment in daily activities), and HIV-associated dementia (marked impairment in cognitive functioning).
HIV-associated dementia is a severe type of HIV-associated neurocognitive disorder, affecting up to 5% of patients on antiretroviral therapy. Patients exhibit a combination of severe cognitive, motor, and behavioral dysfunction that interferes with daily functioning. Manifestations of this condition include short-term memory loss, slowed information processing, reading and comprehension difficulties, and difficulty learning new information. Behavioral changes include apathy and dulling of personality. Prognosis is generally poor, with a life expectancy of less than one year in untreated cases.
Management
The current mainstay in treating patients with HAND to prevent progressive neurological complications is with antiretroviral therapy. A CD4+ count <200 and lack of antiretroviral treatment are significant risk factors for cognitive decline.
Non-pharmacologic measures of treatment include managing other comorbidities and risk factors such as hypertension, hyperlipidemia, diabetes, tobacco use and hepatitis C.
Components of a healthy lifestyle such as proper nutrition, sleep hygiene, regular exercise, and limiting the use of alcohol and other drugs are also recommended to help with the overall health of the brain. Additionally, engaging the brain in regular mental activities can further slow down the progression of HAND. This can include completing brain puzzles, reading, learning a new language, socializing with friends, and participating in group activities.
Course
HAND does not follow a typical course, while symptoms remain typically mild and stable in the majority of patients on antiretroviral therapy. Patients may only experience problems with memory, concentration, dulling of personality or irritability, while others may have difficulties with cognition, mood, and motor function. Current research suggests that patients with asymptomatic cognitive impairment have a two-fold increased risk of progression to symptomatic HAND. Further research can be done on whether individuals with mild neurocognitive disorder eventually progress to HIV-associated dementia.
References
Websites
Journal Articles
Zenebe Y, Necho M, Yimam W, Akele B. Worldwide Occurrence of HIV-Associated Neurocognitive Disorders and Its Associated Factors: A Systematic Review and Meta-Analysis. Front Psychiatry. 2022;13:814362. Published 2022 May 31. doi:10.3389/fpsyt.2022.814362
Hong S, Banks WA. Role of the immune system in HIV-associated neuroinflammation and neurocognitive implications. Brain Behav Immun. 2015;45:1-12. doi:10.1016/j.bbi.2014.10.008
Louboutin JP, Strayer DS. Blood-brain barrier abnormalities caused by HIV-1 gp120: mechanistic and therapeutic implications. ScientificWorldJournal. 2012;2012:482575. doi:10.1100/2012/482575
Thompson LJ, Genovese J, Hong Z, Singh MV, Singh VB. HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology. Int J Mol Sci. 2024;25(9):4697. Published 2024 Apr 25. doi:10.3390/ijms25094697
Rosca, E.C., Albarqouni, L. & Simu, M. Montreal Cognitive Assessment (MoCA) for HIV-Associated Neurocognitive Disorders. Neuropsychol Rev 29, 313–327 (2019). https://doi.org/10.1007/s11065-019-09412-9
Ho M, Lim K, Sharma R, et al. HIV-associated dementia. Reference article, Radiopaedia.org (Accessed on 22 Jan 2026) https://doi.org/10.53347/rID-7274
Rourke SB, Bekele T, Rachlis A, et al. Asymptomatic neurocognitive impairment is a risk for symptomatic decline over a 3-year study period. AIDS. 2021;35(1):63-72. doi:10.1097/QAD.0000000000002709
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