CATIE News

• U.S. researchers studied the motor functions of 354 long-term survivors of HIV
• 69% of participants had some degree of movement problems, such as muscle coordination
• 29% of these cases were classified as “severe”, but most motor dysfunction was mild

In the early 1980s when the HIV pandemic was recognized, doctors soon began to document the impact of this virus on the brain. As explained in our previous CATIE News bulletin, HIV can affect important brain functions such as memory and thinking clearly (such changes are part of a cluster of problems called HIV-related neurocognitive disorder; HAND). However, today these problems are usually minimal in the average HIV-positive person in Canada and other high-income countries thanks to effective HIV treatment (ART).

The virus can also have an impact on what scientists call motor functions – muscle coordination, reflexes and muscle strength – which affect people’s ability to move, including their ability to walk. To explore motor function and HIV infection in the current era, scientists at several centres in the U.S. collaborated in a study of 354 people who had long-standing HIV infection. Such studies are important because as HIV-positive people age, they will probably experience an accumulation or layering of factors, such as cardiovascular and metabolic conditions, that can adversely affect brain health.

The scientists found that nearly 70% of participants had some degree of motor dysfunction; in most people this was mild. However, in nearly 30% of the participants with motor dysfunction, this problem was classed as “severe” by the scientists. Issues such as cardiovascular disease and a history of AIDS-related complications affecting the brain were linked to an increased risk of motor dysfunction. There was less of an association between neurocognitive issues such as HAND and motor dysfunction.

The present study is important because it paves the way for additional studies where HIV-positive people will be monitored over the long term so as to better understand the drivers of motor dysfunction and to find out if interventions can stabilize or reverse it.

Study details

Participants were recruited from four clinics in the following cities:

• Galveston
• Los Angeles
• New York
• San Diego

Participants underwent extensive assessments with a focus on neurocognitive and motor functions. The medical records of participants were also scrutinized for a history of HIV-related complications that could affect the central nervous system, or CNS (i.e., the brain and spinal cord). Here is a list of some of those complications:

• CNS lymphoma
• CNS toxoplasmosis
• CNS tuberculosis
• cryptococcal meningitis
• CMV (cytomegalovirus) encephalitis
• neurosyphilis
• PML (progressive multifocal leukoencephalopathy)

Participants’ history of cardiovascular disease was also reviewed as this can affect brain health.

The average profile of participants when they entered the study was as follows:

• age 60 years
• 73% men, 27% women
• current CD4+ cell count – 538 cells/mm³
• length of HIV infection – 24 years
• distribution of viral load readings: undetectable viral load (less than 50 copies/mL) – 82%; viral load between 51 and 999 copies/mL – 10%; viral load greater than 1,000 copies/mL – 7% (percentages do not add up to 100% because of rounding)

The scientists described the study participants as “medically complex.”

Results

In their analysis, the scientists found that motor dysfunction was “common,” occurring in 69% of participants. However, the researchers noted that in most of these people it was mild, with 29% of motor dysfunction diagnoses being what they termed “severe.”

The distribution of motor dysfunction was as follows:

• abnormalities in walking – 54%
• abnormal coordination of muscles – 39%
• reduced strength – 25%
• abnormal reflexes – 24%

Motor dysfunction associated with walking was in part driven by injury to the nerves in the feet and legs, a condition called peripheral neuropathy.

HAND

Some of the assessments done in the study were for neurocognitive impairment. The scientists found that the distribution of neurocognitive impairment was as follows:

• symptom-free neurocognitive impairment – 16%
• cognitive impairment with symptoms – 46%

A total of 8% of participants had HIV-related dementia and 7% of participants had had 1 or more previous episodes of HIV-related CNS complications.

Intersection with cardiovascular disease

Cardiovascular disease can affect the health of the brain. Arteries supply oxygen-rich blood and nutrients to the brain. If the supply of blood is reduced because of cardiovascular disease, then brain health can decline.

The scientists found that participants who had normal neurocognitive function or symptom-free neurocognitive impairment tended to have lower rates of cardiovascular disease – between 21% and 25%. In contrast, participants who had symptoms of cognitive impairment tended to have higher rates of cardiovascular disease – between 30% and 39%.

According to the scientists, “demographics, musculoskeletal [issues], alcohol use and other immunovirological variables were not associated with [HIV-related motor dysfunction].”

Bear in mind

• In this group of medically complex people, scientists found that motor dysfunction was common. This problem manifested itself most frequently with walking, followed by muscle coordination and muscle strength.
• Motor dysfunction was associated with cardiovascular disease and with prior CNS complications related to HIV infection.
• The researchers think that injury to the brain caused by ongoing cardiovascular disease adds yet another layer of motor impairment to that caused by HIV. They stated that “there is precedent for such layering of CNS diseases in other neurodegenerative conditions [such as Alzheimer’s disease and vascular dementia].”
• The scientists noted that their study’s findings are not applicable to younger HIV-positive people.

About this study’s design

The scientists collected data from one point in time for each participant. Studies like this one are cross-sectional in nature. Cross-sectional studies are good at finding associations, but because of built-in limitations they can never prove what scientists call “cause and effect.” That is, cross-sectional studies cannot prove what causes a problem. However, such studies can find associations between a disease and possible causes. Studies of more robust designs can then be undertaken to uncover the causes of a problem and evaluate ways to address it. Cross-sectional studies are a good first step in trying to understand a biomedical issue and can be done more cheaply than several other types of studies.

For the future

More research needs to be done on HIV-related motor dysfunction. The scientists of the present study think that this problem “may be the end result of neurologic multimorbidity, akin to the systemic multimorbidity that has become an increasingly recognized feature of [chronic HIV infection in the current era].” Such research could lead to early identification of the drivers of HIV-related motor dysfunction and ways to prevent, stabilize or reverse muscle problems.

Resources

Exploring the impact of aging on the brains of HIV-positive and HIV-negative people – CATIE News

HIV and cardiovascular disease – CATIE factsheet

—Sean R. Hosein

REFERENCES:

1. Robinson-Papp J, Gensler G, Navis A, et al. Characteristics of motor dysfunction in longstanding HIV. Clinical Infectious Diseases. 2020; in press.
2. Navia BA, Jordan BD, Price RW. The AIDS dementia complex: I. Clinical features. Annals of Neurology. 1986;19(6):517-524.
3. Elicer IM, Byrd D, Clark US, et al. Motor function declines over time in human immunodeficiency virus and is associated with cerebrovascular disease, while HIV-associated neurocognitive disorder remains stable. Journal of NeuroVirology. 2018;24(4):514-522.
4. Debroy P, Lake JE, Malagoli A, et al. Relationship between grip strength and non-alcoholic fatty liver disease in men living with HIV referred to a metabolic clinic. Journal of Fragility and Aging. 2019;8(3):150-153.
5. Dastgheyb RM, Sacktor N, Franklin D, et al. Cognitive trajectory phenotypes in human immunodeficiency virus-infected patients. Journal of Acquired Immune Deficiency Syndromes. 2019;82(1):61-70.
6. Kuhn T, Jin Y, Huang C, et al. The joint effect of aging and HIV infection on microstructure of white matter bundles. Human Brain Mapping. 2019;40(15):4370-4380.
7. Sanford R, Strain J, Dadar M, et al. HIV infection and cerebral small vessel disease are independently associated with brain atrophy and cognitive impairment. AIDS. 2019;33(7):1197-1205.
8. Nichols MJ, Gates TM, Soares JR, et al. Atrophic brain signatures of mild forms of neurocognitive impairment in virally suppressed HIV infection. AIDS. 2019;33(1):55-66.
9. Yu B, Pasipanodya E, Montoya JL, et al. Metabolic syndrome and neurocognitive deficits in HIV infection. Journal of Acquired Immune Deficiency Syndromes. 2019;81(1):95-101.