Reliably Measuring Cognitive Change in the Era of Chronic HIV Infection and Chronic HIV-Associated Neurocognitive Disorders.

HIV infection has become a chronic disease managed across the life span. In this context, the cognitive health of HIV infection needs to have methods for monitoring over time, in order to better anticipate HIV-associated neurocognitive disorder (HAND) trajectories in relation to biomarkers, and predict prognosis and especially the risk of dementia as People Living with HIV (PLHIV) age. In this chapter, we critically review several statistical frameworks to quantify cognitive change. We then provide a critical review of naturalistic longitudinal studies and selected randomized clinical trials assessing neurocognitive change as a primary outcome in PLHIV, conducted since the advent of the combined antiretroviral therapy era (censored January 2019). Doing so, we distinguish between PLHIV who were treated early and did not experience AIDS (CDC 1993), versus treated late, after experiencing AIDS and more severe immune compromise. Highlighting strengths and limitations of these studies, we emphasize that issues of reliability pertaining to the use of neuropsychological tests need careful consideration for the robust quantification of cognitive change, including measurement error, practice effect, inter-individual variability, baseline level of functioning, demographic effects, timeframe between testing intervals, normative longitudinal data, and operationalization of clinically meaningful neurocognitive change. In addition, issues pertaining to longitudinal analyses including type, amount and pattern of missing data and/or participant attrition, regression toward the mean, and survivor bias need to be properly addressed. We conclude by proposing future research directions with emphasis on research translation to clinical participants.