Impact of Delayed HIV Diagnosis and Treatment on Dementia Risk in Later Life.

Background: Delayed HIV diagnosis and treatment may increase the risk of developing dementia later in life. We evaluated whether low CD4 count (<200 cells/µL) prior to first known use of antiretroviral therapy (ART)-a proxy for delayed HIV diagnosis or treatment-was associated with risk of age-associated dementia. Methods: We conducted a retrospective cohort study (2000-2023) among U.S. adults with HIV aged ≥50 years, all on ART and dementia-free at baseline. The exposure of interest was low pre-ART CD4 count. Dementia diagnoses were identified via electronic health records. The association of low pre-ART CD4 with incident dementia was evaluated using Fine-Gray subdistribution hazard models, accounting for the competing risk of death and adjusting for sociodemographic and clinical confounders. Sub-analyses examined dementia risk among individuals who had low pre-ART CD4 but demonstrated CD4 recovery to ≥500 cells/µL after ART initiation. Results: Among 21 354 people with HIV on ART (mean age 54; 87% men; 46% White, 23% Black, 21% Hispanic, 4% Asian), 30% had pre-ART CD4 < 200 cells/µL. Over a mean follow-up of 7 years, 618 were diagnosed with dementia. Low pre-ART CD4 was associated with greater risk of dementia (adjusted hazard ratio [aHR]: 1.33, 95% CI: 1.13-1.57). CD4 recovery with ART attenuated but did not eliminate dementia risk (aHR: 1.17, 95% CI: 0.85-1.60). Conclusions: Low CD4 count prior to ART-reflecting delayed HIV diagnosis or treatment-was associated with higher dementia risk. Continuing assertive HIV screening and prompt ART initiation in the community will be important to support long-term cognitive health in people with HIV.