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.
"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 Mikaela.
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 patient's 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 Ujjwal Neogi.
This study was funded by grants from the Swedish Research Council, the Karolinska Institute Consolidator Grant, and the Novo Nordisk Foundation. One of the researchers has served on speaker bureaus for Abbott, Nestlé, Nutricia, Reckitt, and Yakult; received research funding from Chiesi and GSK; and acted as a consultant for PrecisionBiotics outside this study. Two of the researchers are employees of Olink Ab Sweden, whose technology was used in the study. One of the researchers is employed by Farmaceutici S.p.A.. Chiesi Farmaceutici S.p.A. but was not involved in the current study. Others none to declare.
Publication
" Host Plasma Microenvironment in Immunometabolically Impaired HIV Infection Leads to Dysregulated Monocyte Function and Synaptic Transmission Ex Vivo ", Mikaeloff F, Gelpi M, Escós A, Wang T, Gupta S, Olofsson A, Akusjärvi SS, Schuster S, Naval P, Sood V, Nikouyan N, Knudsen AD, Vestad B, Høgh J, Hov JR, Benfield T, Trøseid M, Pawar V, Rucevic M, Benfeitas R, Végvári Á, O'Mahony L, Savai R, Björkström NK, Lourda M, de Magalhães JP, Weiss S, Mardinoglu A, Varshney MK, Karlsson AC, Syed YA, Nielsen SD, Neogi U
Adv Sci (Weinh) 2025 Feb;():e2416453
