| |
HIV Found in New Brain Cells, Should HAART Start Earlier To Prevent Brain Damage
|
| |
| |
"This is the first time that anyone has demonstrated active replication of HIV virus in a cell type other than T cells," said study senior author Ronald Swanstrom......People infected with HIV sometimes delay going on HAART, Swanstrom said. "Our research will help further understand what's going on in the central nervous system of patients who are still alive and in tissue that's accessible in the clinical setting, i.e. CSF. If these individuals knew there was an AIDS virus replicating independently in their CNS, it might affect their decision when to start treatment with HAART."
Changes in brain function in early HIV infection: A reliable indicator of disease prognosis? - (10/07/11)
Diminished cognitive function will develop in about half of individuals infected with HIV, which may include deficits in memory, attention, psychomotor capabilities, or verbal fluency. Evidence of cognitive decline in HIV infection has implications for prognosis, reduced survival time, and increased risk of death.. "These findings indicate that changes in brain function are occurring very early in HIV infection, and subclinical alterations in functional connectivity may reflect vulnerability to cognitive decline,". Xue Wang and colleagues from Northwestern University (Chicago and Evanston, IL) and North Shore University Health System (Evanston), used functional magnetic resonance imaging (fMRI) to obtain blood-oxygen-level-dependent measurements in multiple brain regions that yield information on resting-state brain connectivity. They compared the measurements collected in HIV-infected (less than 1 year) and healthy subjects. The authors report "prominent changes" between the two groups in the functional connectivity of visual networks, which have a role in visuo-motor coordination. Based on these findings, they conclude that functional connectivity measurements may be a useful, noninvasive tool for identifying neurological involvement and central nervous system injury early in the course of HIV infection.
HIV-1 Replication in the Central Nervous System Occurs in Two Distinct Cell Types - May Explain Persistent HIV Brain Damage - (10/07/11)
"Less severe neurological problems associated with HIV-1 infection such as minor cognitive impairments may also be increasing, indicating that neurological disorders will remain a problem for HIV-1-infected subjects in the future......Our results demonstrate that HIV-1 can replicate in at least two cell types within the CNS in association with the development of dementia. "HIV replication in the CNS can contribute to neurocognitive decline, so the ability to detect features of the CSF viral population associated with viral replication in the CNS may provide new opportunities to guide interventions prior to the development of overt neurological disease"...."We found that genetically compartmentalized CCR5-tropic (R5) T cell-tropic and macrophage-tropic HIV-1 populations were independently detected in the CSF of subjects diagnosed with HIV-1-associated dementia".....however, HIV-1 in the cerebrospinal fluid (CSF) can decay slowly with the initiation of therapy in some subjects with HAD, suggesting a longer-lived cell type as the origin of this virus.....suggesting that autonomous viral replication is occurring in the CNS of subjects with more severe neurological disease......The insufficient CNS penetration of some antiretroviral drugs or viral resistance may allow HIV-1 to persist in the CNS during the course of therapy.....Less severe neurological problems associated with HIV-1 infection such as minor cognitive impairments may also be increasing [10], [11], indicating that neurological disorders will remain a problem for HIV-1-infected subjects in the future
Can Age-Associated Memory Decline Be Treated? - (10/06/11)
"Pharmacologic interventions accompanied by cognitive-training interventions may be effective in the remediation of diminishing cognitive abilities. At least two studies have shown that memory can be improved by cognitive training and that detectable brain changes accompany these improvements"
"This is the first time that anyone has demonstrated active replication of HIV virus in a cell type other than T cells," said study senior author Ronald Swanstrom......People infected with HIV sometimes delay going on HAART, Swanstrom said. "Our research will help further understand what's going on in the central nervous system of patients who are still alive and in tissue that's accessible in the clinical setting, i.e. CSF. If these individuals knew there was an AIDS virus replicating independently in their CNS, it might affect their decision when to start treatment with HAART."
Research has shown that when the HIV infects the central nervous system, it can lead to the development of a severe neurological disease called HIV-associated dementia (HAD). The advent of highly active antiretroviral therapy, or HAART, has helped reduce HAD. But some studies show that HAART may not offer complete protection from less severe HIV-associated neurological problems, nor might it always help to reverse it. As people live longer with AIDS, their risk of developing neurologic problems may increase.
New research for the first time may have pinpointed a possible explanation for the problem, one that might also help predict who is at greatest risk for HAD.
Scientists led by researchers from the University of North Carolina at Chapel Hill School of Medicine have discovered that some people diagnosed with HAD have two genetically distinct HIV types in their cerebrospinal fluid (CSF), the clear fluid found in the spaces around and inside the brain and spinal cord. What's more, these variants are not detected in HIV circulating in the blood, and one of them could be present years before the onset of dementia. The detection of these viruses in the CSF is evidence that they are growing in the central nervous system.
In a study published October 6, 2011 in the journal, PloS Pathogens, one of the two HIV variants found in CSF reproduces in immune system T cells, as does the virus growing in the blood. But the other type does not. It infects and replicates in macrophages, another white immune cell that engulfs and digests foreign material, including bacteria."This is the first time that anyone has demonstrated active replication of HIV virus in a cell type other than T cells," said study senior author Ronald Swanstrom, PhD, professor of biochemistry and biophysics and director of the UNC Center for AIDS Research.
During their own clinical investigations, Swanstrom's current collaborators, neurologists Richard R. Price, MD and Serena Spudich, MD, at the University of California, San Francisco had been collecting blood and CSF samples from patients who had either HIV-associated dementia or other severe neurological defects. Samples were collected with written informed consent from the patients' families. These were the samples used for the current study.
"After the start of therapy, we looked at the rate at which the virus disappeared," Swanstrom said. "We know that HIV in the blood disappears quickly when you go on therapy, and that's because the virus is growing in T cells, which have a very short half-life," the period of time it takes for a substance undergoing decay to decrease by half. Infected T-cells decay by half every one to two days
But for half of the patients in the new study, HIV growing in the cerebrospinal fluid decayed very slowly, several weeks to one month. "This is evidence the virus is actually being produced by a cell with a longer half-life, and not a T-cell," Swanstrom said.
The researchers also found that the slow-decaying HIV had a particular attraction, or "tropism," to macrophages and were able to infect them.
"Those viruses are known to exist in autopsy brain studies. It has been known for ten years that a subset of HIV-infected patients have slow decay of the virus in the CSF, and it's also been known for a long time that you can find macrophage-tropic virus in the brain," Swanstrom said. "But no one has ever brought the two together in a way that makes sense and could give you a tool to evaluate what's going on the brain by looking at cerebrospinal fluid."
The study also found HIV-infected macrophages present in a CSF sample two years before the patient was diagnosed with dementia. Swanstrom said this tells us there's information in the CSF that potentially could predict disease progression. "Is it bad to have these viruses around even if you don't get a diagnosis of dementia? And are they potentially causing cognitive damage that can be reversed with HAART?"
To explore these and other questions, Swanstrom and Price of UCSF again will collaborate under a 5-year, $3 million grant from the National Institute of Mental Health to expand the research in HIV patients who don't have dementia and are starting therapy. The new study will look for biomarkers in the CSF in the form of HIV variants or other immune protein information that may predict improvement, stability or decrease in cognitive capacity during therapy.
In the new project, Swanstrom's UNC team will include Joseph J. Eron, MD, professor of medicine and Director of the UNC Center for AIDS Research Clinical Core, Kevin Robertson, PhD, clinical psychologist in the department of neurology, and Angela Kashuba, PharmD, associate professor, Eshelman School of Pharmacy and director, UNC Center for AIDS Research Clinical Pharmacology and Analytical Chemistry Core.
People infected with HIV sometimes delay going on HAART, Swanstrom said. "Our research will help further understand what's going on in the central nervous system of patients who are still alive and in tissue that's accessible in the clinical setting, i.e. CSF. If these individuals knew there was an AIDS virus replicating independently in their CNS, it might affect their decision when to start treatment with HAART."
Changes in brain function in early HIV infection: A reliable indicator of disease prognosis? - (10/07/11)
HIV-1 Replication in the Central Nervous System Occurs in Two Distinct Cell Types - May Explain Persistent HIV Brain Damage - (10/07/11)
|
|
| |
| |
|
|
|
