A new study reveals that a significant proportion of people living with HIV (PWH) on long-term antiretroviral therapy remain at risk of immune and metabolic complications despite successful viral suppression. The findings highlight a pressing need for precision medicine approaches to improve long-term health outcomes for PWH.
Researchers from Karolinska Institute, Sweden, in collaboration with Rigshospitalet Copenhagen, used a precision medicine approach, analyzing blood samples from 158 people living with HIV from the Copenhagen Comorbidity Cohort (COCOMO) to better understand the health of the PWH who are on long-term therapy. They used advanced machine learning and multi-omics analysis—combining RNA, proteins, and metabolites—to uncover the causes of ongoing immune activation and metabolic imbalances, which can increase the risk of heart and brain diseases.
The work is published in Advanced Science.
“Our findings show that even with effective HIV treatment, a proportion of PWH on long-therapy remain at risk of health complications due to ongoing immune and metabolic disturbances that can be predicted using multi-omics data,” says Flora Mikaeloff, postdoc at the Department of Oncology-Pathology and the first author of the study.
“The study highlights the need for new strategies that, in addition to suppressing the virus, by targeting metabolic health, which could be key to improving long-term health outcomes for PWH who adhere to the treatment,” says Mikaeloff.
The impact on brain function
The study also explored the impact on brain function using lab-grown brain organoid models and found that metabolic imbalances affect neuronal activity. “By using the cutting-edge 3D brain organoid model, we identified the potential link between long-term HIV infection, inflammation, and cognitive decline,” says Ujjwal Neogi, Docent at the Department of Laboratory Medicine and the lead author of the study.
“By identifying key biomarkers, we can move toward early detection and precision medicine approaches to improve patients’ health outcomes.”
While this study provides crucial insights into the metabolic and immune challenges faced by PWH, it is limited by its sample size and cohort demographics, which may not fully represent the global HIV population. Additionally, the cross-sectional nature of the study does not establish causation between metabolic disruptions and long-term health risks.
“We are expanding our study across three countries to follow a large cohort of PWH over time, aiming to validate key findings on metabolic imbalances and chronic inflammation while developing targeted interventions to improve long-term health outcomes,” says Neogi.
