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Low CD4 Nadir - Impact of Delayed HIV Diagnosis and Treatment on Dementia Risk in Later Life
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Download the PDF here
Download the PDF here
Open Forum Infectious Diseases, 22 January 2026
Abstract
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.
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Comparison of dementia risk after age 50 between individuals with and without HIV infection: 58% Higher Risk, 10 years Earlier
https://www.natap.org/2024/HIV/060324_01.htm
By age 80, 25.8% of PWH and 13.8% of PWOH had been diagnosed with dementia, corresponding with an unadjusted hazard ratio of 1.98 (95% CI 1.64-2.39). After adjustment for sociodemographic, substance use, and clinical factors, including frequency of outpatient visits, the risk of dementia among PWH remained elevated (vs. PWOH, adjusted hazard ratio = 1.58, 95% CI 1.31-1.92).
The average age at dementia diagnosis was 67 years in PWH (SD = 9) and 78 years (SD = 11) in PWOH. Of the 96 (out of 117) PWH with an HIV RNA measurement at dementia diagnosis, 87 (91%) had HIV RNA less than 200 copies/ml.
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