Update on Neuropsychological Issues in HIV Infection
March 20, 2012
And the more that I travel, and the farther I go, the more that I learn, but the less I know. -- Various
CROI 2012 had a large number of presentations on neuropsychological issues, easily the most of any CROI. At the end of the conference, however, we were left with more questions than answers.
A series of oral presentations explored the natural history of neurological issues in HIV-infected patients, as well as potential markers and treatment options. The first of these presentations featured new data from the CHARTER study.
The CHARTER study team, based at the University of California-San Diego, is a leading group studying neurological issues in people with HIV. One of the group's major findings to date is that asymptomatic cognitive impairment is highly prevalent, even among HIV-infected people with an undetectable viral load and a high CD4+ cell count. The question is: Does asymptomatic impairment predict the development of later neurocognitive problems, or is it unrelated?
The CHARTER group looked at this question. It found that there did appear to be a relationship between asymptomatic impairment and the worsening of cognitive disorders. Functional performance measures such as paper-and-pencil tests were found to be better predictors of future symptoms than patient self-report. Lower CD4+ cell nadir, lower CD4+ cell counts, hepatitis C coinfection and being a woman all increased the risk of future symptoms.
After the CHARTER presentation, a British group discussed using positron emission tomography (PET) scans to assess brain inflammation by tracking activation of microglial cells. This inflammation was correlated with cognitive problems. The researchers concluded that inflammation in the brain may lead to symptomatic cognitive problems.
A group from the U.S. gauged inflammation based on the presence of certain proteins measured by magnetic resonance spectroscopy (MRS). It concluded that the inflammation may begin early in HIV infection, and that antiretroviral medications reduce -- but do not normalize -- the inflammation.
Meanwhile, researchers also worked to add to the list of markers of neuropsychological problems. Another study in the oral session found that soluble CD163, which promotes inflammation, correlates with neuropsychological problems.
So now we have a growing list of ways to measure neuropsychological problems in the brain. But are they truly useful for predicting who will develop problems? A themed poster discussion came to the rescue -- at least partly -- by highlighting efforts to develop tools to diagnose neuropsychiatric problems and predict their progression.
In this session, a CHARTER study noted a relationship between waist circumference and neuropsychological impairment. It suggested that central obesity is more damaging than high body mass index, which in fact showed up as protective against neuropsychological problems.
An Italian group examined markers of cardiovascular risk and neuropsychological performance. The factor that emerged most strongly was the level of high-density lipoprotein (HDL), with higher levels more protective against memory (verbal recall) problems.
An Australian group found metabolic abnormalities in the brains of HIV-infected patients, with duration of HIV infection and some cardiovascular risk factors strongly associated. Another presentation, from the Washington University School of Medicine, included data showing that blood flow in the brain is lower in HIV-infected people than in uninfected people. Looking at "resting state energy expenditure," this group found a distinctive signature among HIV-infected people that was different from Alzheimer's. The researchers suggest that this technique may be used for differential diagnosis.
Speaking of neurologic disorders that emerge as people age, a poster from Johns Hopkins University found that increasing age was the most significant factor linked to greater problems with memory. Of interest was that memory problems occurred across all levels of neuropsychological impairment, including people with no symptoms.
Finally, a symposium entitled "The Long and Winding Road of HIV Complications" included a couple of presentations that contributed to the topic of neuropsychological problems. (You can watch a webcast of the symposium here.) In the final presentation of the session (and of the conference), Edwina Wright reviewed the screening, diagnosis and management of neuropsychological problems, particularly in patients with controlled viremia. She identified various potential causes of neuropsychological problems and options for management. These include what she calls a "legacy effect" involving three possible levels of severity: 1) the central nervous system (CNS) was infected early in the patient's disease, prior to treatment with combination antiretroviral therapy; 2) poor CNS viral control is occurring; and 3) ongoing infection or inflammation is taking place.
For the legacy effect, if symptoms are stable, Wright suggests monitoring and annual review. For poor CNS viral control, she suggests switching to a more potent antiretroviral regimen or one with a higher penetration of CNS. And for ongoing infection/inflammation, she recommends intensification of the regimen in terms of antiviral potency or better CNS penetration, although she noted that evidence is lacking for the benefits of this approach.
But to what extent are such interventions truly necessary? Earlier in the same session, Amy Justice presented a talk she titled, "Aging With HIV: One Size Does Not Fit All." She suggested that the conclusions many of us have reached about the "early" onset of comorbidities among people with HIV should be adjusted based on the population. In HIV, she noted, the available cohorts are younger than the general population. After adjustment for this difference, she found that the age of cancer diagnoses, which initially appeared to be 12 to 23 years "early," was actually only 3 to 5 years sooner than among the HIV-uninfected population.
She also addressed "guideline fatigue" for providers, in which they face multiple, overlapping sets of guidelines. Screening and treatment, she contended, are a balancing act. In favor of screening is what we believe to be the reduced risk of morbidity, usually based on clinical trials in which participants had no other active morbidity. Against screening are the risks of screening and treatment, which include over-burdening primary care providers and the risk of polypharmacy, generally defined as more than 5 medications -- a situation that may end up causing more problems for our patients in the long term than treating them for a condition that may not dramatically worsen in their lifetimes.
So, when we take all of this new information, together, what do we have? Should we screen HIV-infected patients for neuropsychological problems? Do providers have time for proper neuropsychological testing? Do we know what to do with the screening results?
The answer is: We just don't know for sure yet.
Copyright © 2012 Remedy Health Media, LLC. All rights reserved.
This article was provided by TheBodyPRO. It is a part of the publication The 19th Conference on Retroviruses and Opportunistic Infections.
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