Longitudinal Association Between Prefrailty/Frailty and HIV-associated Neurocognitive Disorder (HAND): a Mexican Prospective Study

Abstract Geriatric syndromes such as frailty may be more prevalent and occur earlier in people aging with HIV, negatively impacting outcomes like cognition. Cross-sectional data show strong associations between pre-frailty/frailty and HIV-associated neurocognitive disorders (HAND). However, prospective studies suggest baseline HAND increases frailty risk, while pre-frailty/frailty do not predict HAND onset. We aimed to investigate longitudinal association between baseline frailty and HAND category progression. Longitudinal analysis of 194 participants aged ≥50 years from Mexico City referral center. Two standardized geriatric assessments performed at least one year apart. HAND defined using Antinori criteria, frailty by Fried phenotype. Inverse probability weighted Cox models adjusted for confounders from directed acyclic graph (age, educational level, detectable viral load, diabetes, stroke, ischemic heart disease) determined association between frailty and HAND progression. Median age 55 (53–61) years; 167 (86%) men; median follow-up 2.3 (1.6–3.1) years. Baseline: 129 (66.4%) robust, 62 (31.9%) pre-frail, 3 (1.5%) frail. No longitudinal association between pre-frailty/frailty and HAND progression was observed in this cohort (32 progression events; adjusted HR = 0.63, 95% CI 0.27–1.48; p = 0.29). No evidence of a prospective association between prefrailty/frailty and HAND category progression was observed in this cohort; most participants remained cognitively stable. To our knowledge, this is the first study describing HAND trajectories and their relationship with prefrailty/frailty in older adults with HIV in Mexico and Latin America.