The human immunodeficiency virus (HIV) targets the immune system, leading to acquired immunodeficiency syndrome (AIDS) if left untreated. For individuals with HIV, the virus can affect the brain, causing neurological complications. These can include a form of dementia, collectively known as HIV-associated neurocognitive disorder (HAND).
How HIV Affects the Brain
HIV can enter the central nervous system (CNS) early in infection, often within days. This occurs through a “Trojan horse” mechanism, where infected immune cells like monocytes and CD4+ T lymphocytes cross the blood-brain barrier (BBB). The BBB acts as a protective shield, regulating substance passage into the brain. HIV proteins, like Tat, can disrupt BBB tight junctions, facilitating entry of infected cells and viral particles.
Once inside the CNS, HIV predominantly infects brain-resident immune cells like microglia and macrophages, and to a lesser extent, astrocytes. Neurons are generally not directly infected, but suffer indirect damage. Infected and activated glial cells release inflammatory molecules, neurotoxins, and viral proteins, creating a neuroinflammatory environment. This chronic inflammation disrupts neuronal function, leading to injury and loss.
Forms and Symptoms of Neurocognitive Impairment
HIV-associated neurocognitive disorder (HAND) is an umbrella term for a spectrum of cognitive, motor, and behavioral changes in people living with HIV, ranging from mild to severe. HAND is categorized into three classifications based on cognitive decline severity and its impact on daily functioning.
The mildest form is Asymptomatic Neurocognitive Impairment (ANI), where individuals show measurable cognitive deficits on neuropsychological tests but no significant interference with daily activities. Mild Neurocognitive Disorder (MND) is a more noticeable impairment, characterized by cognitive difficulties greater than expected with normal aging, causing mild interference with daily life. Symptoms can include frequent forgetfulness, difficulty with complex tasks, language problems, or attention deficits.
The most severe manifestation is HIV-Associated Dementia (HAD), historically known as AIDS Dementia Complex. HAD involves significant acquired impairment in multiple cognitive domains like memory, concentration, and information processing, leading to a substantial decline in performing daily tasks independently. Beyond cognitive issues, HAD can present with motor symptoms such as clumsiness, poor balance, tremors, and loss of fine motor control. Behavioral changes like apathy, lethargy, irritability, or diminished emotional responses may also be observed.
Identifying and Managing the Condition
Diagnosing HIV-associated neurocognitive disorder involves a comprehensive evaluation to identify cognitive impairment and rule out other causes. Healthcare professionals use neurocognitive testing, assessing areas like attention, memory, executive functions, language, and visuospatial skills. Screening tools such as the International HIV Dementia Scale (IHDS) and the Montreal Cognitive Assessment (MoCA) help identify individuals who might benefit from more in-depth neuropsychological assessment.
A physical examination and thorough medical history are important to exclude other conditions that can mimic HAND symptoms, such as opportunistic infections, neurological diseases, nutritional deficiencies, or substance abuse. Management strategies focus on improving daily function and quality of life. These include cognitive rehabilitation to help individuals develop coping mechanisms for cognitive challenges. Lifestyle adjustments, such as maintaining a structured routine and using aids like lists, can also be beneficial. Addressing co-occurring mental health conditions like depression or anxiety is an important part of comprehensive care.
The Role of Antiretroviral Therapy (ART)
Before widespread effective antiretroviral therapy (ART) in the mid-1990s, HIV-associated dementia (HAD) was a common and devastating complication of advanced HIV infection. It occurred in many individuals with low CD4+ T cell levels and high viral loads, often a sign of late-stage disease. HAD significantly impacted quality of life and often led to death within a year without treatment.
The introduction of ART has dramatically transformed HIV disease and its neurological complications. ART reduces viral load in the body, including the central nervous system, which in turn decreases inflammation and allows the immune system to recover. This has led to a significant decline in HAD incidence and severity, making the severe form of dementia much less common.
While severe HAD has become rarer, milder forms of HAND, such as asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorder (MND), remain prevalent, affecting many people living with HIV even with effective viral suppression.
Despite the profound benefits of ART, HAND can still persist or develop due to several factors. Chronic brain inflammation, even with suppressed viral replication, continues to play a role in neuronal damage. The aging HIV population is a growing concern, as older individuals living with HIV may experience cognitive issues influenced by both HIV and age-related changes or comorbidities like cardiovascular disease and diabetes. Early ART initiation is important, but even with sustained viral suppression, the central nervous system can act as a viral reservoir, contributing to ongoing issues. Research explores these challenges, including the potential for certain ART medications, like nucleoside reverse transcriptase inhibitors (NRTIs), to protect against cognitive decline by blocking inflammatory processes.