Introduction
The neurocognitive dysfunctions that are associated with HIV infection are commonly referred to as HIV-associated neurocognitive disorder (HAND). HIV can enter the central nervous system (CNS) during the early stages of infection. These infections, when become persistent CNS HIV infection and inflammation, play a role in the development of HAND. Interestingly, even when systemic viral suppression is achieved, the brain can still act as a reservoir for ongoing HIV replication. This poses a significant challenge as HAND can persist in patients receiving combination antiretroviral therapy (CART), impacting their survival, quality of life, and everyday functioning. Addressing this issue is crucial.
Patients infected with the human immunodeficiency virus (HIV) often experience a range of neuropsychiatric conditions. These conditions encompass cognitive disorders as well as symptoms related to mood and anxiety. In the past, prior to the introduction of antiretroviral therapy, many of these neuropsychiatric disorders remained untreated, leading to significant morbidity and mortality among affected individuals. The majority of these disorders were a result of untreated opportunistic infections associated with acquired immunodeficiency syndrome (AIDS), such as toxoplasmosis and encephalitis. The emergence of highly active antiretroviral therapy (HAART) played a pivotal role in reducing the incidence of neurocognitive disorders. HAART.
What Causes HIV-Associated Neurocognitive Disorder?
During the acute phase of human immunodeficiency virus (HIV) infection, the virus can directly cross the blood-brain barrier. However, it is during the chronic inflammatory phase that cognitive changes become evident. The impact of HIV on the brain involves various components, including monocytes, macrophages, and white matter. HIV replicates within microglia, which are considered the brain's immune cells. These changes contribute to the clinical signs and symptoms associated with neurocognitive disorders in individuals with HIV. However, it is important to note that not all HIV patients will develop these disorders, as there are several identified risk factors discussed below.
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Low Nadir CD4 Count: Multiple studies have demonstrated a correlation between the severity of HIV disease, indicated by a low nadir CD4 count, and the risk of developing neurocognitive disorders. Furthermore, the longer duration of HIV infection, the presence of AIDS-defining lesions, and increases the risk of HIV-associated dementia. Notably, these studies have suggested that neurocognitive dysfunction in these patients may have a sustained impairment component that is not reversible, even with antiretroviral therapy. Improvements in laboratory parameters following highly active antiretroviral therapy (HAART) did not show a significant association with neurocognitive impairment, indicating that neural injury resulting from HIV may persist despite antiretroviral treatment.
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Coexistent Cardiovascular Disease and Obesity: HIV patients with underlying cardiovascular risk factors or existing cardiovascular disease have an elevated risk of dementia compared to the general population.
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Advanced Age: While there is a higher prevalence of neurocognitive disorders in HIV patients aged 50 years or older, it remains unclear whether this is solely due to HIV infection or a result of advanced age itself.
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History of Toxoplasmosis: A previous history of toxoplasma infection, particularly in individuals with latent toxoplasma infections, has been associated with an increased risk of neurocognitive deficits. This risk appears to be independent of CD4 cell counts.
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Coinfection With Hepatitis C: The relationship between hepatitis C coinfection and the risk of neurocognitive disorders in HIV patients is still debated. Some studies suggest a clear risk when both infections are present, while others do not find evidence of increased neurocognitive impairment in individuals coinfected with both viruses.
What Are the Symptoms of HIV-Associated Neurocognitive Disorder?
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The symptoms present as difficulties with concentration, memory, and executive functioning. As the disease progresses, additional symptoms such as depressive symptoms, psychomotor retardation, irritability, and subclinical motor signs may appear. These motor signs can include tremors (shaking of the hands or other parts of the body) and hyperreflexia (overactive muscle reflex response). With further progression, clinical features may include myelopathy (nervous system defect affecting the spinal cord), dementia (loss of memory), neuropathy (pain or weakness due to nerve damage) and even Parkinson-like features (tremors in hands and other body parts).
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The severity of HIV infection and the use of antiretroviral treatment (ART) play a significant role in the presentation of HAND. Patients with severe diseases, such as dementia, are more likely to have untreated HIV infection with low CD4 cell counts. They may not be receiving any ART or maybe on ineffective treatment regimens. On the other hand, patients on ART tend to experience a slowly progressive decline in neurocognitive function with milder deficits.
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HIV-associated dementia typically exhibits subcortical dysfunction. This can manifest as attention-concentration impairment, depressive symptoms, and impaired psychomotor functions. Cognitive deficits may include memory impairment, impaired executive functioning, and apathy.
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In cases of mild neurocognitive decline, the predominant features are impaired attention and working memory. Higher executive functioning may also be affected. These deficits may not always be clinically apparent but can result in difficulties with reading and maintaining concentration during conversations or activities when symptoms are present. Mild forms of neurocognitive decline typically do not involve motor dysfunction.
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CNS viral escape syndrome is a rare condition seen in patients undergoing antiretroviral therapy. It is characterized by severe new-onset neurological deficits resulting from HIV replication in the central nervous system (CNS), despite adequate peripheral viral suppression. In most cases, there is also evidence of drug resistance in the HIV strain present in the cerebrospinal fluid (CSF).
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Detectable CSF HIV RNA can be observed in patients without neurocognitive dysfunction. When CNS viral escape syndrome is suspected, CSF analysis for HIV RNA levels and genotype testing is recommended to diagnose the condition and determine appropriate changes to the antiretroviral regimen based on resistance patterns.
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Immune reconstitution inflammatory syndrome (IRIS) is another rare cause of new-onset neurocognitive symptoms in individuals with HIV. It occurs due to HIV-related central nervous system infection and is characterized by severe encephalitis, widespread abnormalities in the white and gray matter on radiographic imaging, and increased CD8 cell count in the CSF.
How to Treat HIV-Associated Neurocognitive Disorder?
Psychiatric medications are often used to manage mood disorders in these patients. Various types of antidepressants have shown moderate symptomatic relief, including selective serotonin reuptake inhibitors, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors. Psychostimulants may be prescribed for fatigue and apathy. Research on psychotic and manic symptoms in HIV-positive patients is limited, but some studies indicate a higher incidence of extrapyramidal symptoms in individuals with psychosis. Certain mood stabilizers may have neurotoxic effects or interact with antiretroviral drugs, so caution is necessary. Several drugs are considered potentially neuroprotective, such as Memantine, Pentoxifylline, Selegiline, Nimodipine, and Peptide T, but only Selegiline has demonstrated efficacy in studies.
Conclusion
Organic brain syndrome can present with various symptoms depending on the specific disease. Common symptoms include agitation, confusion, long-term loss of brain function (dementia), and severe, short-term loss of brain function (delirium). Diagnostic tests for organic brain syndrome may include blood tests, neuropsychological testing, EEG, head CT scan, head MRI, and lumbar puncture. Treatment approaches are tailored to the underlying condition, often involving rehabilitation and supportive care to address lost abilities. Medications may be prescribed to manage aggressive behaviors associated with certain conditions.
