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SHARE: Neurological Complications of HIV
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            What are the neurological complications of AIDS and HIV?

HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immunodeficiency syndrome), if untreated. While HIV primarily affects the immune system, it can lead to a wide range of severe neurological disorders, particularly if HIV goes untreated and progresses to AIDS, the most advanced stage of HIV infection. Many of the most severe neurological conditions can be prevented with antiretroviral therapy or ART, the standard treatment for HIV.

While HIV does not directly invade nerve cells (neurons) in the brain, it infects cells called glia that support and protect neurons, putting brain function at risk. HIV can enter the brain early in the course of infection. HIV infection in the brain can also trigger an inflammation that may damage the brain and if left untreated can cause symptoms that may include:

Confusion and forgetfulness
	Difficulty concentrating
	Behavior changes
	Headaches
	Anxiety and depression
	Movement problems, including a lack of coordination and difficulty walkingHIV infection can also damage the peripheral nerves can cause progressive weakness and loss of sensation in the arms and legs. HIV infection can cause parts of the brain involved in learning and information processing to shrink.

Other nervous system complications that can occur as a result of HIV infection include:

Pain
	Seizures
	Strokes
	Shingles
	Difficulty swallowing
	Fever
	Vision loss
	Coma
	Problems with bladder control or sexual functioningThese symptoms may be mild in the early stages but can become increasingly severe as HIV progresses to AIDS and remains untreated.

The nervous system may be affected directly by the HIV virus, by certain cancers and infections that result from a weakened immune system. Other neurological complications may be influenced by, but are not directly caused by, the HIV virus.

People with HIV (PWH) experience faster decline in memory and thinking skills (cognitive function) as they age than those without HIV. This is known as HIV-associated neurocognitive disorders (HAND), which include a wide range of disorders and brain changes, some of which have no symptoms, and some of which result in severe neurocognitive impairment. The more serious forms of HAND also are referred to as AIDS dementia complex (ADC) or HIV-associated dementia and primarily occur in people with more advanced HIV infection. Signs and symptoms include encephalitis (inflammation of the brain), behavioral changes, and a gradual decline in cognitive function. People with ADC also experience movement problems and loss of dexterity (skill in performing tasks, especially with the hands) and coordination. When left untreated, ADC can be fatal. A neurologist can evaluate and manage ADC. Neuropsychologists can perform formal neurocognitive testing for people with progressively worsening symptoms of HAND.  Early treatment with antiretroviral drugs can change the trajectory of neurological complications of HIV infection and prevent severe symptoms such as ADC and spinal cord and peripheral nerve impairment. In addition, HAND has now mostly shifted toward asymptomatic or mild cognitive impairment.

What are the latest updates on the neurological complications of HIV?

NINDS, a part of the National Institutes of Health (NIH), is the nation’s leading federal funder of research on neurological disorders. NINDS, the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Mental Health (NIMH), and other components of NIH conduct research related to HIV and AIDS and fund research at major institutions and universities. The NIH Office of AIDS Research (OAR) coordinates HIV research across NIH.

NINDS-funded projects are investigating how HIV damages the brain and the reasons neurological injury persists even in individuals whose illness is well-controlled with combined antiretroviral therapy (cART). Some of this research focuses on the contributions of immune cells in the brain called microglia that are sent into overdrive by HIV infection and may be harmful to neurons as a result.

While ART prevents the HIV virus from replicating, it is not a cure. Once the virus enters the brain, it can stay there for the rest of the person’s life. It is important that individuals with HIV continue lifelong treatment to keep the virus suppressed. Even with successful ART treatment, HIV can still produce viral proteins and RNA but not a fully replicating virus. The viral RNA and protein can still contribute to slower damage to brain cells and inflammation. Thus, PWH on effective ART continue to have low levels of immune activation and neuroinflammation, even after the virus is no longer replicating in the nervous system. Recent findings suggest that this neuroinflammation may be caused by defective HIV proviruses (genetic material from a virus that is integrated into the DNA of a person’s cells), viral RNA, and/or low levels of viral proteins from infected central nervous system (CNS) cells (i.e., macrophages, microglia, and astrocytes). The ongoing neuroinflammation has been associated with cognitive impairment in PWH. A recent study suggests that the integration of HIV into CNS myeloid cells initiates a process that promotes a chronic neuroinflammatory and neurodegenerative state.

Other studies are exploring how HIV damages the blood-brain barrier and are investigating new formulations of cART as well as drug delivery methods that are better able to cross into the brain. Many people whose infection is successfully suppressed with cART experience a reactivation of the virus when they stop treatment, possibly because a reservoir of inactive HIV is maintained in the brain. This research is a first step toward developing a means to render the virus permanently dormant or even to rid the brain of all traces of the virus.

Scientists are examining whether HIV accelerates brain aging and how natural aging affects the development and symptoms of HAND. Several studies are aimed at understanding the role of genetics in HAND, as well as the complex interactions that occur between chronic HIV infection and other aging-related co-morbidities such as cerebrovascular disease and Alzheimer’s disease and related dementias (AD/ADRD).

Researchers are studying AIDS dementia complex and cognitive dysfunction in HIV to better understand how the death of neurons contributes to these conditions. Investigators are also studying inflammatory mechanisms associated with HIV dementia and how early proteins produced by that the virus contribute to the loss of cognitive functions in infected individuals by changing the way cells communicate. Other researchers are currently investigating genetic differences in HIV viral variants that enhance their ability to infect the brain and survive in the central nervous system. By comparing these HIV mutant strains to other viral variants that are less likely to penetrate the brain, researchers hope to develop vaccines that may have the potential to prevent neurological symptoms of HIV in people who already have the virus.

NINDS conducts research into how the weakened immune systems of PWH can lead to neurological illnesses. NINDS investigators are studying tuberculous meningitis (TBM) and cryptococcal meningitis co-infection in PWH to find evidence-based interventions to improve survival. NINDS investigators are studying the JC virus, which can reproduce in the brains of people with impaired immune systems and cause progressive multifocal leukoencephalopathy (PML). In one small NINDS study, the anti-cancer drug pembrolizumab showed promise in slowing or stopping the progression of PML. Additional research is needed to confirm results, which could help revolutionize treatment for similar chronic infections in immune compromised individuals.

Researchers are also investigating how HIV affects not only the brain but also the peripheral nervous system, where it causes peripheral neuropathyand associated neuropathic pain in some people. Some of these studies focus on determining how HIV and ART treatments cause these conditions, while others aim to develop new treatments for neuropathic pain or examine how brain activity differs in PWH with and without pain.

The National NeuroAIDS Tissue Consortium, a project supported jointly by NINDS, NIMH, and other NIH institutes is collecting tissue from PWH who have suffered from dementia, mild to moderate neurocognitive impairment, and other neurological complications. The Consortium also gathers brain tissue from such individuals after death. The samples are then distributed to researchers around the world for use in their research.

For research articles and summaries on the neurological complications of HIV and AIDS, search PubMed, which contains citations from medical journals and other sites.

file-medical

Learn About Clinical Trials

Clinical trials are studies that allow us to learn more about disorders and improve care. They can help connect patients with new and upcoming treatment options.

How can I or my loved one help improve care for people with HIV and AIDS?

Consider participating in a clinical trial so clinicians and scientists can learn more about HIV/AIDS. Clinical research with human participants helps researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of participants are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.

For information about participating in clinical research visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with HIV and AIDS at Clinicaltrials.gov, a searchable database of current and past clinical trials and research results.

Where can I find more information about the neurological complications of AIDS and HIV?

More information is available from the following resources:

HIVinfo.NIH.gov

MedlinePlus

National Institute of Allergy and Infectious Diseases
866-284-4107

NIH Office of AIDS Research
800-448-0440

National Institute of Mental Health
866-415-8051

National Institute on Aging
800-222-2225

amfAR, the Foundation for AIDS Research
212-806-1600

Elizabeth Glaser Pediatric AIDS Foundation
888-499-4673National NeuroAIDS Tissue Consortium
866-668-2272
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Order publications from the NINDS Catalog

The NINDS Publication Catalog offers printed materials on neurological disorders for patients, health professionals, and the general public. All materials are free of charge, and a downloadable PDF version is also available for most publications. Health Information
  
    

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      Last reviewed on March 22, 2024
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