Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline

Abstract

Objective: While HIV-associated neurocognitive disorders (HAND) remain prevalent despite combination antiretroviral therapy (CART), the clinical relevance of asymptomatic neurocognitive impairment (ANI), the most common HAND diagnosis, remains unclear. We investigated whether HIV-infected persons with ANI were more likely than those who were neurocognitively normal (NCN) to experience a decline in everyday functioning (symptomatic decline).Methods: A total of 347 human participants from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort were NCN (n 5 226) or had ANI (n 5 121) at baseline. Neurocognitive assessments occurred approximately every 6 months, with median (interquartile range) follow-up of 45.2 (28.7-63.7) months. Symptomatic decline was based on self-report (SR) or objective, performance-based (PB) problems in everyday functioning. Proportional hazards modeling was used to generate risk ratios for progression to symptomatic HAND after adjusting for baseline and time-dependent covariates, including CD41 T-lymphocyte count (CD4), virologic suppression, CART, and mood.Results: The ANI group had a shorter time to symptomatic HAND than the NCN after adjusting for baseline predictors: adjusted risk ratios for symptomatic HAND were 2.0 (confidence interval [CI] 1.1-3.6; p 5 0.02) for SR, 5.8 (CI 3.2-10.7; p , 0.0001) for PB, and 3.2 (CI 2.0-5.0; p , 0.0001) for either SR or PB. Current CD4 and depression were significant time-dependent covariates, but antiretroviral regimen, virologic suppression, and substance abuse or dependence were not. Conclusions:This longitudinal study demonstrates that ANI conveys a 2-fold to 6-fold increase in risk for earlier development of symptomatic HAND, supporting the prognostic value of the ANI diagnosis in clinical settings. Identifying those at highest risk for symptomatic decline may offer an opportunity to modify treatment to delay progression.

Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study

“…11 In our study, progression from ANI to either a MND or HAD stage was seen in 7/24 (29%) cases in HIV1 individuals over 4 years of follow-up. In contrast, 14/ 24 (58%) HIV1 individuals remained at ANI over 4 years, whereas 3/24 (13%) HIV1 individuals improved from ANI to normal cognition.…”

Evidence-based perspectives on the implementation of screening for neurocognitive impairment in HIV

“…55 Similar results were found in a Canadian cohort where virological suppression rates were much higher than in the US study, but there was still a 32% risk of progression from ANI to other grades of HAND, compared to 17% risk of progression from normal cognitive function to symptomatic HAND. 56 Limitations to both these studies lie in the use of "time to event" analysis, which in this context assumes that once a patient changes from ANI to more severe grades of HAND, they cannot revert to having ANI or normal cognitive function.…”

Self-Reported Decline in Everyday Function, Cognitive Symptoms, and Cognitive Function in People With HIV

“…There are limited data on more accurate and reliable measures of everyday performance, such as third-party observation or performance-based measures. 12,13 This has crucial implications for the interpretation of longitudinal studies in which the risk of change from ANI to MND is measured, such as the United States CHARTER cohort, 39 the Canadian OHTN Cohort, 6 and the French Aquitaine cohort. 40 For example, in the Ottawa cohort, depression was a major risk factor for change from ANI to MND.…”

“…30 Each cognitive test was converted to an age-, sex-, and education-standardized Z-score using normative mean values and SD. Normative data for the computerized tests were provided by Cogstate from Europe, United States of America, South East Asia, and Australia/New Zealand, frequencymatched for age (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50), and 51+ years; minimum cell size n = 145), sex (157 female, 377 male), and education (university/further education, n = 243, or secondary school, n = 291). The normative population excluded individuals with clinical or functional impediments to test performance, and subsets of these data had been used previously to measure cognitive function in HIV+ adults.…”