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Neuropsychological Impairment Detected Early in Course of HIV

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Findings Support Early ART Treatment

"We know that the virus [HIV] gets across the brain pretty quickly,

and then we think that there are these central nervous system

reservoirs, so it’s hiding out in the brain," session comoderator Dr.

Beau Ances noted in an interview. "The question is, in these individuals

with primary HIV infection, is there any kind of signature that we can

see even early on that indicates the brain is being affected? And if so,

would that affect our treatment strategy for these individuals, because

primarily, our way of diagnosing and also following an individual is

using the plasma viral load or their CD4 count."

Not

only did a sizable proportion of patients already have

neuropsychological impairments at baseline, but motor performance

continued to decline before ART initiation, he noted. Thus, the findings

may speak to a need to intervene earlier in the course of disease.

"What

was interesting was, one, these deficits are present and they are

present early in the disease. And, two, some domains seem to be

preferentially affected compared to others," Dr. Ances said.

"From

my point of view, this is very interesting in that it does bring up

some considerations as to when to start [ART] or a neuroprotective

medication," he commented. "This would suggest that maybe we need to

consider ART in these individuals and start them much earlier, since

there is damage that seems to be going on. And then targeted cognitive

rehabilitation in certain domains may be very important."

Dr. Ances is assistant professor of neurology at the Washington University School of Medicine in St. Louis. He disclosed being on the advisory committee for Lilly and working on an antidementia drug trial for Pfizer.


 

FROM THE CONFERENCE ON RETROVIRUSES AND OPPORTUNISTIC INFECTIONS

SEATTLE – Almost half of patients with newly diagnosed HIV infection appeared to have impaired neuropsychological functioning, according to the findings of a prospective longitudinal study involving 70 men. Initiation of antiretroviral therapy halted this decline but did not reverse it.

Before starting antiretroviral therapy (ART), study patients, who were an average of 4 months into their infection, had declines over time in the motor neuropsychological domain and a composite measure of motor function and processing speed, Dr. Julia Peterson of the University of California, San Francisco, reported at the Conference on Retroviruses and Opportunistic Infections.

Dr. Julia Peterson

Nearly half of patients started ART during follow-up, and after doing so, these patients had stabilization – but not improvement – in both measures.

"These findings suggest that while performance in certain neuropsychological domains may improve with repeated testing, a decline in motor performance is measurable in patients with untreated HIV infection, and that this decline may be attenuated with early antiretroviral treatment," Dr. Peterson commented.

"Although it is difficult to discern the reason for the negative trajectory of the motor performance initially in primary HIV infection," an imaging study has shown "accumulating inflammation in the frontal white matter during the same period of time, so this may correspond to the motor dysfunction that we are seeing," she said. Furthermore, as suggested by other research, "there is detection of neuropathy in this same primary infection cohort, which may also lead to motor dysfunction."

When asked whether there might have been a confounding effect of patients’ psychological reaction to such a serious new diagnosis, she acknowledged that was possible, especially at the first study visit.

"I don’t know the perfect way to factor in every single thing that might be affecting the patient at that visit: It could be drug use, it could be anxiety, it could be depression, it could be another diagnosis," she said. However, neuropsychological performance at baseline did not correlate with mental health symptoms.

"Lymphocytic meningitis is common in this setting within the first few months of seroconversion," noted Dr. Rodger MacArthur of Wayne State University in Detroit, who attended the session. "So how did you adjust or correct for that, for individuals who had either symptomatic meningitis or silent meningitis?"

Only a few patients in the cohort were found to have meningitis, and they were excluded from longitudinal analyses, Dr. Peterson said.

Explaining the study’s rationale, she noted, "There are many reports on the persistence of mild neurological and cognitive impairment in patients with chronic HIV infection who are on suppressive treatment. Yet there is limited study on the neuropsychological testing performance early during infection."

The investigators evaluated patients repeatedly over time with 11 neuropsychological tests assessing performance in five domains. They also used two composite measures: the total Z score (reflecting all 11 tests) and the NPZ4 score (reflecting four tests of motor and processing speed). The latter is "more relevant in the clinical setting," Dr. Peterson noted.

The enrolled patients had a median age of 36 years and a median of 16 years of education, and 79% had a history of drug use. On average, they were 125 days post HIV exposure and had a CD4 count of 555 cells/mm3.

At baseline, 42% of the patients performed more than one standard deviation below the normative mean in at least two neuropsychological domains, meeting criteria for asymptomatic neurocognitive impairment or mild neurocognitive disorder.

Longitudinal analyses showed that before starting ART, the patients had declines over time in the motor domain (P = .012) and the NPZ4 composite measure (P = .027).

Forty-seven percent of the patients started ART during follow-up, a median of about 32 weeks after HIV exposure and at a median CD4 count of 433 cells/mm3.

After starting ART, these patients had stabilization in the motor domain (P = NS) and NPZ4 measure (P = NS). They also had new improvement in the executive function domain (P = .001).

"At any point when treatment is initiated, motor performance stabilizes to practically no change and no improvement, thus suggesting ... each patient will maintain any sort of accumulated impairment," commented Dr. Peterson.

Performance in the remaining domain studied, memory, did not change significantly, either before or after ART initiation.

"Treatment was not randomized," she acknowledged. Also, "there was no well-matched control group, so we had to rely on published norms, which may or may not be congruent with our own study population. It is not clear whether baseline or accrued impairment reflects premorbid factors or is actually the effect of HIV."

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