We evaluated the relationship of advancing age to neurocognitive (NC) performance over time in a large cohort of individuals who had initiated their first virologically suppressive antiretroviral therapy (ART) regimen.
This analysis included ART-naïve individuals from 7 randomized ART parent trials of the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) cohort. All underwent annual NC testing with the ACTG NeuroScreen. Only assessments done after the participants had been on ART for at least 2 years were included in this analysis. Overall performance, calculated by comparison to normative data from HIV negative individuals, was summarized using mean z-scores across the 4 tests (NPZ-4). Impairment was defined as ≤ -2.0 SD on one test or ≤ -1.0 SD on two tests. Uni- and multi-variable repeated measures regression models evaluated predictors of NC performance. Predictors evaluated included entry demographics, smoking, injection drug use (IDU), hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) serostatus, history of stroke, ART regimen type, pre-ART nadir CD4 and plasma viral load (PVL) and as well as time-updated PVL and CD4. Variables significant at p≤0.10 were eligible to enter the multivariable models.
The cohort comprised 3,313 individuals with a median age at parent entry of 38 [IQR 31, 45; 12% over age 50], 36% Black, non-Hispanic; 22% Hispanic; CD4 nadir median 221 [IQR 82, 324]. Median duration of NC follow-up was 3.4 years (range 0-6.4). Considering the cohort as a whole, NC performance improved year on year such that 23% were classified as impaired at the first analyzed visit compared to only 13% in the last analyzed visit. After adjusting for the expected effects of age using norms from HIV–negative individuals, the odds of NCI impairment at a visit among HIV+ participants increased for each decade of advancing age (OR 1.18 [1.1,1.25]). Virologic suppression, which was maintained at 91% of follow-up visits, was not related to NC worsening.
Despite continued virologic suppression and overall NC improvement in the cohort as a whole, older individuals tended to have worse NC performance, after consideration of concurrent predictors, than younger individuals. Future studies should evaluate potential mediators of the adverse effects of age on NC trajectories, such as inflammation and vascular risk factors.