Kaiser Permanente analysis underlines importance of early identification, treatment of HIV
Waiting to start antiretroviral therapy (ART) can have long-term health implications for people diagnosed with HIV — specifically, increased risk of dementia in later life, according to new Kaiser Permanente research.
A study published in the journal Open Forum Infectious Diseases reported that patients treated for HIV who had a low CD4 count before they started ART were more likely to be diagnosed with dementia years later. The CD4 count is a measure of the strength of the immune system.
The investigators looked at medical records for 21,354 older Kaiser Permanente patients with HIV, focusing on the years between 2000 and 2023. A low CD4 count before treatment was an indication the patient was experiencing HIV-related immunosuppression, explained lead author Jennifer Lam, PhD, a research scientist with the Kaiser Permanente Division of Research (DOR).
HIV treatment guidelines have evolved over time. Delaying HIV treatment until CD4 counts lowered was common protocol in previous years. However, more recently HIV practitioners recommend drug treatment right away after diagnosis.
“These findings reinforce the importance of continuing proactive HIV screening and prompt treatment,” Lam said. “This is compelling evidence that there can be long-term implications of a delay in getting on medications.”
On average, the patients in the analysis were followed for 7 years. Of 21,354 people aged 50 and older and on ART, 618 were diagnosed with dementia. There was a 33% greater likelihood of a dementia diagnosis for those with a low CD4 count before treatment. For those whose CD4 counts improved after starting treatment, the increased dementia risk was reduced but not eliminated, the study found.
“People are living longer with HIV, and it’s important that we understand how their risk of chronic diseases of aging might differ from people without HIV,” said senior author Michael Silverberg, PhD, MPH, and associate director of DOR’s Behavioral Health, Aging and Infectious Disease Section. “Our HIV clinicians wanted to know how much of the increase in cognitive impairment they saw was due to things that can be modified, such as blood pressure, and timing of ART.”
The study included a broad range of dementia diagnoses, including Alzheimer’s disease, vascular dementia, Parkinson’s dementia, dementia with Lewy bodies, frontotemporal dementia, and other or unspecified dementia.
“The finding that delayed ART can raise the risk of age-related dementia is eye-opening,” said study co-author Craig E. Hou, MD, a neurologist with The Permanente Medical Group. “Dementia risk involves multiple factors, from lifestyle to genetics, and can be even more complex among people with chronic disease. Having more evidence about what contributes to our patients’ cognitive issues will help us better understand and prevent dementias in the future.”
Broadening evidence on HIV, dementia risk
In a separate recent paper published in the journal AIDS, the Kaiser Permanente study team expanded on its previous findings about the increased risk of dementia in people with HIV. The team reported in 2021 new evidence that older people with HIV had nearly double the rate of dementia than older people without HIV. While the risk decreased over time for both groups, the study found that over 16 years, the risk remained higher for those with HIV.
In a December 2025 follow-up paper published in the journal AIDS, the study team expanded its analysis to a larger group of people in multiple Kaiser Permanente regions, over a longer period of time (23 years) and found similar results as the 2021 study. They also looked at additional questions, such as whether the dementia trends differed by race, ethnicity, or sex, and found they did not.
“This is the benefit of using large electronic health datasets such as those available at Kaiser Permanente,” Lam said. “It allows us to study important but relatively uncommon health outcomes such as dementia, and to also be able to examine patterns across population subgroups.”
The researchers said the findings highlight the importance of staying attentive to cognitive health as people with HIV age, so that any concerns can be identified and supported early.
The study on HIV treatment delay was funded by Kaiser Permanente’s Garfield Memorial Fund and by the National Institute of Allergy and Infectious Diseases.
Additional co-authors were Dongjie Fan, MS, and Alexandra Lea, MPH, of the Division of Research; Haihong Hu, MS, and Michael Horberg, MD, of the Mid-Atlantic Permanente Research Institute; Errol Lopez and William J. Towner, MD, of the Department of Research & Evaluation of Kaiser Permanente Southern California; and Catherine Lee, PhD, formerly with DOR.
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About the Kaiser Permanente Division of Research
The Kaiser Permanente Division of Research conducts, publishes, and disseminates epidemiologic and health services research to improve the health and medical care of Kaiser Permanente members and society at large. KPDOR seeks to understand the determinants of illness and well-being and to improve the quality and cost-effectiveness of health care. Currently, DOR’s 720-plus staff, including 73 research and staff scientists, are working on nearly 630 epidemiological and health services research projects. For more information, visit divisionofresearch.kp.org.
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