Cognitive disorders persist in persons with HIV, despite virologically suppressive antiretroviral therapy. We summarize the current evidence on risk factors for cognitive decline in persons with HIV in the modern antiretroviral therapy-era. Recent consensus recommendations have proposed a new approach for defining cognitive impairment in persons with HIV, which distinguishes true cognitive impairment from low cognitive performance alone and considers both HIV and non-HIV-associated causes of brain injury. Adverse mental health, risks associated with substance misuse, and an increasing burden of age-related comorbidities have been highlighted as important contributors toward cognitive decline in this population. Aging may potentiate these risk factors through polypharmacy and drug-drug interactions. Cognitive decline in persons with HIV is likely multifactorial, with contributions from both HIV and non-HIV-associated mechanisms, particularly age-related comorbidities. With an aging community of persons with HIV, screening for risk factors associated with cognitive decline may be crucial to implement appropriate risk reduction strategies.
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