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Ceasing HAART found not to cause neurocognitive decline in healthy patients.

LOS ANGELES -- Relatively healthy individuals who opted to discontinue highly active antiretroviral therapy did not appear to suffer any neurocognitive repercussions and in fact performed better on a standard battery of neuropsychological tests during their drug vacations.

"This was not what we expected," said Kevin Robertson, Ph.D., who presented the findings at the 14th Conference on Retroviruses and Opportunistic Infections.

An initial group of 167 HIV-infected patients was enrolled in the observational, multicenter study when they made a decision to discontinue highly active antiretroviral therapy (HAART).

At study entry, their mean age was 42 years and they had spent 4.5 years on HAART.

They represented a "uniquely healthy population," Dr. Robertson stressed, with a mean baseline peripheral blood CD4 count of 833 cells/mcL and a low viral load (71% had fewer than 50 copies/mL plasma HIV RNA).

A brief neuropsychological battery of tests, including Trail-making A/B and Digit Symbol, was administered at 24 weeks, 48 weeks, 72 weeks, and 96 weeks to assess psychomotor speed, attention, concentration, cognitive sequencing, and shifting cognitive sets--skills known to be affected by HIV.

"We felt that when subjects stopped HAART, it would lead to a decline in neuropsychological performance," said Dr. Robertson, director of neuropsychology and a member of the NeuroAIDS Working Group at the University of North Carolina at Chapel Hill.

In fact, just the opposite occurred, with mean neuropsychological summary (NPZ3) scores improving by 0.22, 0.39, 0.52, and 0.74 during the 96-week study.

Among a group of 46 subjects who eventually decided to reinitiate HAART, there was no significant change in composite neurocognitive scores over 72 weeks of follow-up, although Dr. Robertson noted that the final study group represented a "very small sample size" of 37 patients by week 24 of the follow-up study.

Numerous possible confounding factors were explored by the investigative team from the University of North Carolina; Harvard University, Boston; the University of California, San Francisco; and Baystate Medical Center, Springfield, Mass. However, they statistically ruled out a practice effect, selection bias, or a possible link between neurocognitive function and efavirenz-containing HIV regimens.

"Many people in this room, myself included, have shown improvement [in neurocognitive function] with ART, especially in later disease," Dr. Robertson said during his presentation.

"This study does not suggest you shouldn't take your antiretroviral treatment at all."

"What we know is that HIV gets into the CNS within days.... The virus is presumably chipping away," he said.

He suggested that further research should focus on "potential sources of HAART toxicity on CNS function," because neurocognitive decline did not follow discontinuation of the powerful therapies in healthy subjects who were able to remain off HAART for extended periods of time.


Los Angeles Bureau
Neuropsychological Summary Score Improvement After HAART Discontinuation

Follow-Up in Weeks

24 0.22
48 0.39
72 0.52
96 0.74

Note: Based on a study of 167 HIV-infected patients.
Source: Dr. Robertson

Note: Table made from bar graph.
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Title Annotation:Across Specialties
Author:Bates, Betsy
Publication:Clinical Psychiatry News
Article Type:Clinical report
Date:May 1, 2007
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