Nearly 25% of People with HIV Show Signs of Neurological Problems

		SUMMARY: About one-quarter of HIV positive people, and more than 40% of those with an AIDS diagnosis, show evidence of neurological disorders, most frequently neurocognitive impairment and peripheral neuropathy, according to a study published in the September 28, 2010 issue of Neurology. While specific manifestations have changed since the advent of effective antiretroviral therapy (ART), neurological problems remain common and are associated with increased risk of death.

By Liz Highleyman

The occurrence of frank AIDS-related dementia has declined during the ART era, and modern antiretroviral drugs are less likely to cause neuropathy (nerve damage) than earlier agents such as stavudine (d4T, Zerit) or didanosine (ddI, Videx). But as HIV positive people live longer, they are prone to neurocognitive problems related to aging, which appear to progress faster in this population.

In the present study, Pornpun Vivithanaporn and Christopher Power from the University of Alberta and colleagues looked at the impact of combination ART on the changing incidence (new cases) and prevalence (total cases) of neurological disorders among people with HIV and AIDS, as well as their effects on mortality.

The analysis included patients receiving care in a regional HIV care program in Canada from 1998 -- as combination ART with protease inhibitors came into widespread use -- through 2008. A total of 1651 HIV positive people were evaluated. Most (about 80%) were men, nearly 70% were white, and the average age was 33 years.

Results

	" Of the 1651 patients assessed, 404 (24.5%) had 1 or more neurological disorder.
	Among people with an AIDS diagnosis, the rate rose to 41.0%.
	People with AIDS were nearly twice as likely to have neurological problems as HIV positive people who never had an AIDS diagnosis.
	People with lower current and nadir (lowest-ever) CD4 T-cell counts were more likely to have neurological problems.
	The most common problems were a type of peripheral neuropathy known as symptomatic distal sensory polyneuropathy (DSPN) at 10.0%, and HIV-associated neurocognitive disorders (HAND) at 6.2%.
	About half the patients with any neurological problem had 2 or more disorders.
	The incidence rate of neurological disorders dropped by half over the course of the study, from 12.2% in 1998 to 5.7% in 2007, mostly attributable to decreases in DSPN and HAND.
	A total of 171 patients died during 14,134 person-years of follow-up.
	Participants who had at least 1 neurological disorder had a significantly higher mortality rate than people without such disorders (17.6% vs 8.0%, respectively; P < 0.0001).
	The disparity was particularly apparent for AIDS-related deaths (9.7% vs 3.2%, respectively; P < 0.0001).
	The highest mortality hazard ratios (HR) -- a measure of the magnitude of increased risk of death -- were associated with:
	Opportunistic infections of the central nervous system: HR 5.3, or about 5-fold greater risk of death; HIV-associated neurocognitive disorders: HR 3.1, or about 3 times greater mortality; Presence of any neurological disorders: HR 2.0, or twice the risk.
	Among people with neurological disorders, the risk of AIDS-related death increased according to viral load and CD4 cell count:
	39.0% greater risk per 10-fold increase in plasma viral load; 13.3% greater risk per 100 cells/mm3 reduction in CD4 count.

Based on these findings, the researchers concluded, "The burden and type of HIV-related neurologic disease have evolved over the past decade and despite the availability of combination ART, neurologic disorders occur frequently and predict an increased risk of death."

The frequency of neurological problems seen in this HIV positive population with an average age in the mid-30s was similar to that typically seen in HIV negative people in their mid-50s, the study authors noted in their discussion.

A growing body of evidence indicates that chronic immune activation and persistent inflammation associated with HIV infection contributes to non-AIDS conditions including neurocognitive impairment well before the CD4 cell count drops to a dangerous level. This study supports earlier ART to keep viral load low and CD4 count high as long as possible.

Investigator affiliations: Division of Neurology and Statistical Consulting Centre and Department of Dentistry, University of Alberta, Edmonton, Canada; Department of Pharmacology, Mahidol University, Bangkok, Thailand; Southern Alberta Clinic, Calgary, Canada; Departments of Neurology and Neuroscience, Johns Hopkins University, Baltimore, MD; Departments of Medicine and Medical Microbiology and Infectious Diseases, University of Calgary, Calgary, Canada.

11/16/10

Reference
P Vivithanaporn, G Heo, J Gamble, and others. Neurologic disease burden in treated HIV/AIDS predicts survival: a population-based study. Neurology 75(13): 1150-1158 (Abstract). September 28, 2010.