Neurocognitive status and risk of mortality among people living with human immunodeficiency virus: an 18-year retrospective cohort study

Abstract

HIV-related neurocognitive impairment (NCI) may increase the risk of death. However, a survival disadvantage for patients with NCI has not been well studied in the post-combination antiretroviral therapy (cART) era. Specifically, limited research has been conducted considering the reversible nature and variable progression of the impairment and this area demands further evaluation. We performed multivariable Cox proportional hazards modeling to assess the association between baseline NCI (global T scores) and mortality. A joint modeling approach was then used to model the trajectory of global neurocognitive functioning over time and the association between neurocognitive trajectory and mortality. Among the National NeuroAIDS Tissue Consortium's (NNTC) HIV-infected participants, we found a strong negative association between NCI and mortality in the older age groups (e.g., at age = 55, HR = 0.79; 95% CI 0.64-0.99). Three neurocognitive sub-domains (abstraction and executive functioning, speed of information processing, and motor) had the strongest negative association with mortality. Joint modelling indicated a 33% lower hazard for every 10-unit increase in global T scores (HR = 0.67; 95% CI 0.56-0.80). The study identified older HIV-infected individuals with NCI as a group needing special attention for the longevity of life. The study has considerable prognostic utility by not only predicting mortality hazard, but also future cognitive status.

Figure 1

Flow chart of participation. *Descriptive analysis comparing those with missing data for covariates of interest to those with complete data showed no difference in demographic variables and baseline global T scores. **There is a 12% loss to follow-up.

Figure 2

Kaplan–Meier plot for overall survival. Median survival time = 13.2 years (95% CI 11.4–15.5).

Figure 3

Kaplan–Meier plot stratified by neurocognitive status. Median survival time impaired (global T score ≤ 40) = 11.8 years (95% CI 9.6–15.5). Median survival time unimpaired (global T score > 40) = 14.1 years (95% CI 9.6). *The upper limit of confidence interval for median survival time in unimpaired group is not estimable because of censored data.