| Publication Abstract Display | | Type: Poster | | Title: Higher CD4 nadir is associated with reduced rates of HIV-associated neurocognitive disorders in the CHARTER Study: Potential implications for early treatment initiation. | | Authors: Ellis RJ, Heaton RK, Letendre SL, Badiee J, Munoz-Moreno JA, Vaida F, Clifford DB, Gelman BB, Simpson DM, Grant I, for the CHARTER Group | | Date: 02-16-2010 | | Abstract:Background and Objectives: Indirect evidence suggests that early initiation of antiretroviral therapy (ART) may prevent HIV-associated neurocognitive disorders (HAND). Prevention is important since once HAND occurs, many individuals remain impaired despite effective viral suppression on ART. To determine whether earlier ART initiation protects against HAND, we evaluated the relationship between nadir CD4+ cell counts, a surrogate for worst immunosuppression prior to ART, and risk of HAND.
Methods: Comprehensive medical and neuropsychological (NP) evaluations were performed on 1526 subjects in a multicenter cohort study, CNS HIV Antiretroviral Therapy Effects Research (CHARTER). HAND was diagnosed by comprehensive NP and neuromedical testing according to published criteria. Comorbid conditions contributing to NP impairment were evaluated by a single, experienced NP rater. Nadir CD4 was by self report or observation.
Results: The median [IQR] nadir CD4 was 172 [48-297]. 1080 subjects (71%) took ART and 589 of these (55%) had undetectable plasma viral loads (VL). 799 (52.4%) were NP impaired (NPI), and 692 (45.3%) had significant comorbid conditions. HAND diagnosis was associated with substantial disability as measured by a structured self-report instrument. Higher CD4 nadirs were associated with lower rates of NPI in the entire cohort, and in the subsets with minimal comorbidities and on ART. Among 579 subjects on ART with minimal confounds, the odds ratios (95%CI) and corresponding rates [%] of HAND at CD4 nadir levels of 200-349 (n=127) and ≥350 (n=51) compared to 0-199 (reference, n=401; [47% with HAND] were 0.72 (0.47-1.10) [39%] and 0.57 (0.30-1.10) [33%] (trend Chi-square = 4.9, p=0.03). No "threshold" effect was seen; higher CD4 nadir conferred lower HAND risk at all levels. The association remained significant after adjusting for other predictors including plasma VL, age, sex, ethnicity, and duration of HIV infection.
Conclusions: These findings confirm prior reports that higher nadir CD4 is associated with a reduced risk of HAND. Results held true both for the cohort as a whole and for a subgroup of special interest comprising individuals currently taking ART and having no significant confounds. Because HAND is a common source of disability in HIV+ individuals on ART, these data suggest that earlier treatment initiation may protect patients from HAND |
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