Lowest-ever CD4 Count Predicts Cognitive Impairment

SUMMARY Low nadir CD4 T-cell count before starting antiretroviral treatment raises risk of neurocognitive problems for people with HIV.

By Liz Highleyman

Research over the course of the epidemic has found that people with HIV/AIDS have higher rates of neurocognitive problems ranging from mild impairment to frank AIDS-related dementia. While the risk of severe problems has fallen since the advent of effective antiretroviral therapy (ART), mild-to-moderate impairment remains common.

As described in the July 6, 2011, advance online edition of AIDS, Ronald Ellis and fellow investigators with the CHARTER Group evaluated the probability of neuropsychological impairment and HIV-associated neurocognitive disorders (HAND) in relation to nadir or lowest-ever CD4 cell count before ART initiation.

The analysis included 1525 HIV positive people in the prospective observational CHARTER (CNS HIV Antiretroviral Therapy Effects Research) study. Participants completed comprehensive neurobehavioral and neuromedical evaluations, including a series of standardized neurocognitive tests covering 7 cognitive domains. Such tests can often detect subtle impairment before it affects daily living.

The median nadir CD4 count -- based on self-reports -- was quite low, at 172 cells/mm3, reflecting both people who were infected early, before effective drugs were available, and individuals with HIV diagnosed HIV late after infection. Participants were considered to have HAND if they demonstrated neuropsychological impairment that could not be attributed to other causes.

Results

	Overall, 52% of participants were found to have neuropsychological impairment due to any cause.
	Among impaired participants, 75% were diagnosed with HAND (that is, 39% overall).
	Impaired participants had significantly lower nadir CD4 counts on average than unimpaired patients (median 155 vs 187 cells/mm3, respectively).
	Impaired people were also more likely to be taking combination ART than those without impairment (75% vs 67%, respectively).
	People with higher nadir CD4 counts had a lower likelihood of neuropsychological impairment.
	The researchers calculated that for every 5-unit increase in square-root nadir CD4 cell level, the odds of neuropsychological impairment decreased by 10%.
	Among 589 participants with undetectable viral load on ART, higher nadir CD4 cell remained associated with lower risk of neuropsychological impairment after adjusting for demographic and clinical factors.
	Current CD4 count and viral load, however, were similar in the impaired and unimpaired groups.

These results confirm prior studies suggesting that lowest-ever -- rather than current -- CD4 count is the best predictor of cognitive impairment. People with a history of serious immune dysfunction, therefore, may remain at risk for HAND even after their CD4 count recovers on ART.

Based on these findings, the CHARTER researchers concluded, "Since the risk of neuropsychological impairment was lowest in subjects whose CD4 [cell count] was never allowed to fall to low levels before [combination] ART initiation, our findings suggest that initiation of [combination] ART as early as possible might reduce the risk of developing HAND, the most common source of neuropsychological impairment among HIV-infected individuals."

"We observed that HIV-infected individuals never experiencing low CD4 counts were relatively protected from neuropsychological impairment as compared to those with a history of severe immunosuppression," they elaborated in their discussion. "The depth of immune suppression reached, as indexed by the nadir CD4, might represent an important HIV 'legacy event' that causes irreversible neural injury, contributing to HAND."

"If true, then preventing severe or even moderate immunosuppression by initiating ART as soon as possible might reduce subsequent HAND risk," they recommended. "Our findings further emphasize the importance of identifying HIV- seropositive subjects early in the course of their illness and encouraging ART use to prevent later complications."

Investigator affiliations: University of California San Diego, San Diego, CA; Washington University, St. Louis, St. Louis, MO; University of Washington Seattle, Seattle, WA; University of Texas Medical Branch, Galveston, TX; Johns Hopkins University, Baltimore, MD; Mount Sinai School of Medicine, New York, NY.

7/8/11

Reference
RJ Ellis, J Badiee, F Vaida, et al. (CHARTER Group). Nadir CD4 is a Predictor of HIV Neurocognitive Impairment in the Era of Combination Antiretroviral Therapy. AIDS. July 6, 2011.