Risk factors for HIV-associated neurocognitive impairment and frailty in aging people with HIV in Latin America: a systematic review

As people living with HIV (PWH) in Latin America and the Caribbean (LAC) have longer life expectancy due to improved access to antiretroviral therapy (ART), complications such as HIV-associated neurocognitive impairment (NCI; including HIV-associated neurocognitive disorder [HAND]) and frailty are increasingly more prevalent. We aimed to identify the risk factors for neurocognitive impairment and frailty among aging PWH in LAC. We conducted a systematic review following PRISMA guidelines. We searched five databases that reported on NCI, HAND or frailty in PWH in LAC. Eligible studies included observational studies, clinical trials or case series. Data were extracted on study characteristics, diagnostic tools utilized, prevalence estimates (when available) and associated risk factors of each condition of interest. A total of 83 studies met inclusion criteria: 71 focused on NCI (including HAND) and 14 on frailty (2 on both NCI and frailty). NCI and HAND prevalence ranged from 11% to 89%, with most studies using brief cognitive screening tools (NCI) rather than formal neuropsychological testing (HAND). Risk factors for both NCI included older age, lower education, female sex, low CD4 counts and psychosocial factors. ART use did not consistently protect against NCI. Only a small subset of studies employed complete neuropsychological test batteries, imaging or biomarker analysis. Frailty studies, primarily from Brazil, reported prevalence ranging from 8% to 50%. Frailty risk factors included older age, female sex, depression, low CD4 counts, malnutrition, and unemployment. Some studies reported no or inconsistent associations with traditional HIV characteristics. NCI and frailty are common and underrecognized conditions affecting aging PWH in LAC. Region-specific diagnostic approaches and targeted interventions are urgently needed to improve cognitive and functional health outcomes in this population.