Higher Comorbidity Burden Predicts Worsening Neurocognitive Trajectories in People with Human Immunodeficiency Virus

BACKGROUND Age-related comorbidities accumulate faster in people with HIV (PWH) than in those without (PWoH). We evaluated whether a validated multimorbidity scale, the Charlson Index, predicted neurocognitive trajectories in PWH. METHODS Scaled scores a comprehensive neuropsychological battery were averaged across all visits. Multilevel modeling examined between- and within-person predictors of global neurocognition. At the between-person level, averaged Charlson scores were examined as a predictor of neurocognitive change rate, covarying for HIV disease characteristics. Within-persons, visit-specific Charlson Index was used to predict fluctuations in global neurocognition at the same and next visit, covarying for disease measures. RESULTS Participants were 1195 PWH (mean baseline age 43·0; SD 9·7 years) followed for a mean of 7·1 years (range 0·5-20·5). At the between-person level, more rapid neurocognitive worsening correlated with higher (worse) average Charlson scores (standardized β -0·062, SE 0·015; p=0·001) and lower CD4 nadir (standardized β 0·055, SE 0·021; p=0·011), but not viral suppression or average CD4+ lymphocytes (ps > 0·05). At the within-person level, poorer visit-specific neurocognition was related to worse concurrent, but not preceding, Charlson scores (standardized β-0·046, SE 0·015; p = 0·003), detectable HIV viral load (standardized β0·018, SE 0·006; p = 0·001) and higher CD4+ (standardized β0·043, SE 0·009; p < 0·001). CONCLUSION The impact of comorbidities on neurocognitive decline exceeded that of HIV disease factors. Although correlative, the temporal relationships suggested that treatment of comorbidities might improve neurocognitive prognosis for PWH.