Deep Phenotyping of HIV Neurocognitive Complications Among Individuals Residing in High-Income Countries

People living with HIV (PLWH) residing in high-income countries (HICs) are, in theory, well positioned to benefit from clinical care strategies that predict optimal neurocognitive and neuropsychiatric outcomes. However, there is substantial inter-individual variability in access to clinical care, prevalence of co-occurring risk factors, and comorbid health conditions that represent barriers to achieving the full potential of antiretroviral therapy (ART). Complex interactions between these variables translate into heterogeneity in HIV clinical phenotypes, including abnormalities in brain structure and function. The growing population of PLWH in HICs who are now reaching advanced age introduces additional causal pathways of neurocognitive variability among PLWH receiving ART. These patterns foreshadow trends expected to develop globally in response to increased access to ART. This chapter reviews the combination of highly dimensional risk factors for neurocognitive complications among PLWH residing in HICs. We begin with a brief description of the neuropathological, neuroimaging, and neurocognitive signatures of HIV, followed by a summary of controversies regarding the clinical presentation of HIV-associated neurocognitive disorders (HAND), including putative synergies between HIV disease dynamics and advanced age. Finally, we introduce innovative research strategies that have potential to advance the existing conceptual framework of HAND and, ideally, catalyze the development and of clinical interventions needed to achieve HIV treatment and eradication efforts.