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  17th CROI
Conference on Retroviruses
and Opportunistic Infections
San Francisco CA
February 16-19, 2010
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Low CD4 Nadir Predicts Neurocognitive Problems Despite Good CD4 Gains
  17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
Neurocognitive problems persisted in many HIV-infected US residents despite good CD4 gains after starting antiretroviral therapy [1]. People whose lowest-ever (nadir) CD4 count never slipped below 350 had the best chance of averting neurocognitive problems. Those conclusions emerged from a 1525-person analysis of the prospective US CHARTER cohort, inspiring the investigators to "emphasize the importance of identifying HIV-seropositive subjects early in the course of their illness to prevent later complications."
This analysis excluded people with an active opportunistic disease, schizophrenia, or the inability to complete a comprehensive set of neuropsychological tests plus other evaluations. Cohort members averaged 43.2 years in age and 12.5 years of education. Three quarters of the study group were men, and 61% were nonwhite. Median current CD4 count stood at 420 (interquartile range [IQR] 262 to 603), nadir CD4 count at 172 (IQR 48 to 297), and estimated HIV duration at 120 months (IQR 53 to 173). Plasma viral load was undetectable in 895 people (59%).
Only one of these measures differed significantly between 799 people with neuropsychological impairment and 726 without impairment--median CD4 nadir stood at 155 in the impaired group and 187 in the unimpaired group (P = 0.002). Among all cohort members, 25.4% had a nadir below 50, 31.5% had a nadir of 50 to 199, 24.3% had a nadir of 200 to 349, and 18.8% had a nadir at or above 350.
Among all cohort members, a lower CD4 nadir correlated with neuropsychological impairment, though only a CD4 nadir above 349 significantly protected from impairment compared with a nadir below 50:
· CD4 nadir below 50 (reference value): odds ratio (OR) 1.00
· CD4 nadir 50 to 199: OR 0.86, 95% confidence interval [CI] 0.66 to 1.13
· CD4 nadir 200 to 349: OR 0.78, 95% CI 0.58 to 1.03
· CD4 nadir 350 or higher: OR 0.62, 95% CI 0.45 to 0.84
Among people with a plasma viral load below 50 copies, a CD4 nadir of 200 to 349 or above 349 significantly lowered the risk of neuropsychological impairment compared with a nadir below 50. A nadir between 200 and 349 lowered the risk 40%, and a nadir above 349 cut the risk 45%:
· CD4 nadir below 50 (reference value): OR 1.00
· CD4 nadir 50 to 199: OR 0.80, 95% CI 0.54 to 1.19
· CD4 nadir 200 to 349: OR 0.60, 95% CI 0.39 to 0.95
· CD4 nadir 350 or higher: OR 0.55, 95% CI 0.30 to 0.99
The impact of nadir CD4 count on neuropsychological impairment held true in multivariate analyses that weighed relevant neuropsychological variables including age, duration or HIV infection, ethnicity, and race. Nadir CD4 count remained predictive when the investigators excluded people with major neurocognitive comorbidities. Current CD4 count had no impact on risk of neuropsychological impairment.
The CHARTER team speculated that avoiding lower CD4 nadirs by starting antiretrovirals sooner "may reduce the likelihood of HIV-associated neurocognitive disease and associated disability."
1. Ellis R, Heaton R, Letendre S, et al. Higher CD4 nadir is associated with reduced rates of HIV-associated neurocognitive disorders in the CHARTER study: potential implications for early treatment initiation. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 429.
Table 3. Odds Ratios for NP Impairment