Long-term study plays down risk of brain problems in HIV-positive patients

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A small study that followed a group of HIV-positive patients for seven years has found a low risk of disorders of the brain and nervous system. The study’s results were published in the March edition of the European Journal of Neurology.

HIV can gain access to the cerebrospinal fluid that surrounds the brain and spinal cord. While this is known to cause neurological problems such as dementia in patients with severe damage to the immune system, its effects in earlier stages of disease are less clear.

To improve understanding of the effects of HIV on the brain, investigators from Sweden wished to assess the effects of HIV infection in a group of 28 patients without severe damage to the immune system. All of the patients had CD4 cell counts above 280 cells/mm3 at the start of the study, having been infected for a median of 3.5 years.

The investigators carried out tests to measure brain function and psychological performance every year for up to seven years, along with brain scans to examine blood flow and brain structure.

They found no consistent signs of deterioration of the patients’ performance on a range of psychological tests across the study. Tests measured dexterity, speed of movement, language ability, problem solving, concentration, reaction times, attention, short-term memory, abstract thought and the patients’ ability to understand instructions, read, write, perform calculations and draw three-dimensional pictures.

Although a few of the patients' observations were unusual, the researchers could attribute these to other medical problems in each case, including bleeding in the brain and damage to a disc in the spine. However, all of the patients had HIV in the cerebrospinal fluid that surrounds the brain and spinal cord from the very early stages of infection.

“There was not one consistent pathological finding that appeared in several patients. Neither [were we] able to detect any significant decline in the neuropsychological performance,” the investigators write. “Our study lends support to earlier observations that even if the virus is present in the central nervous system the patients need not show any neurological manifestations.”

They also carried out electroencephalograms (EEGs) to measure the patients’ brain activity and their response to external stimuli, including light, touch and sound. Abnormal findings were found more often in patients who had been HIV-positive for longer, but this was not mirrored by any defects in the patient’s function.

There was also no major deterioration in the results from two types of brain scan: single photon emission computed tomography (SPECT), which measures blood flow through the brain, and magnetic resonance imaging (MRI), which provides high-resolution images of the brain’s structure.

None of the patients showed a consistent decline in brain activity patterns or any correlation between the brain scan results and their neurological performance.

“We were not able to discern any decline in the cognitive function or other performance of the nervous system that could be attributed to direct impact of the HIV on the nervous system,” the investigators conclude.

“Our study would give support to an optimistic attitude,” they add. “Although our study had a limited number of patients it sheds light on the neurological development in a group of HIV-infected patients when studied in detail longitudinally up to seven years”.

Five patients died of an AIDS-related condition during the study. Although four of these had neurological diagnoses at the time of death, these developed rapidly, and could not be detected at the last testing before they died. Three of the patients had encephalitis caused by cytomegalovirus, while the fourth had toxoplasmosis in the brain.

Although its results were only published last month, the study was carried out between 1989 and 1996, before modern antiretroviral drug combinations were available.

At the start of the study, 16 (57%) of the patients had received some HIV treatment, rising to 27 (96%) by the end. Treatment mainly consisted of monotherapy with AZT (zidovudine, Retrovir), ddI (didanosine, Videx) or ddC (zalcitabine, Hivid) although twelve patients had also received protease inhibitors by the seventh year of the study.

The effect of preservation of CD4 cell counts by current anti-HIV drug combinations on changes in neurological function remains to be examined in studies similar to the Swedish investigation, using repeated tests and brain scans over many years.

References

Samuelsson K et al. The nervous system in early HIV infection: a prospective study through 7 years. Eur J Neurol 13: 283-291, 2006.