A groundbreaking study unveiled at ESCMID Global 2026 in Munich has revealed that antiretroviral therapy (ART) has a profound impact on reducing the accelerated biological ageing associated with HIV infection. Researchers have demonstrated that, in people living with HIV (PWH), ART can reverse accelerated biological ageing by nearly four years, a discovery poised to revolutionize both clinical monitoring and long-term management of HIV.
The study hinges on the development of an innovative plasma proteomic ageing clock (PAC), a novel biomarker tool designed to estimate biological age based on the proteomic profile of blood plasma. Unlike chronological age, biological age reflects the physiological state of ageing in the body, which can be influenced significantly by disease and treatment. By analyzing intricate patterns across hundreds of plasma proteins, the PAC offers an unprecedented window into the ageing processes altered by HIV and ART.
This tool was rigorously tested using samples from the Swiss HIV Cohort Study (SHCS), a rich longitudinal biobank of blood specimens from individuals with HIV. Initially, the PAC was trained on 941 plasma samples from participants who were successfully managing their infection with ART. Subsequently, the model was validated in an independent cohort of 80 participants who provided 294 serial samples spanning the phases before antiretroviral therapy initiation—when the virus was actively replicating (viraemia)—and during sustained viral suppression post-ART.
Analysis of PAC data paints a stark picture of the biological toll exacted by untreated HIV. During the viraemic phase, participants’ biological age was found to be accelerated by a median of 10 years relative to their chronological age. This acceleration underscores the systemic impact of active HIV replication on physiological systems. Importantly, following approximately 1.5 years of effective ART, this biological ageing acceleration was significantly reduced by a mean of 3.7 years, a change that was highly statistically significant (p = 0.0001). Further longitudinal data suggested that prolonged ART exposure continues to allow the proteomic age to converge towards the individual’s true chronological age, highlighting a degree of biological recovery that is sustained with adherence.
Prior epidemiological and molecular studies have long indicated that HIV infection precipitates premature ageing, likely driven by persistent inflammation and immune dysfunction. This premature ageing elevates risks for comorbidities typically associated with advanced age, such as cardiovascular disease and certain cancers. The current findings lend vital mechanistic insight: by suppressing viral replication with ART, the chronic inflammatory burden reduces, facilitating a reversal of biological ageing acceleration.
Dr. Barry Ryan, lead author and postdoctoral researcher at École Polytechnique Fédérale de Lausanne (EPFL), reflected on the study’s significance. Thanks to the unique SHCS cohort—some of whom had samples collected up to eight years prior to ART initiation—the team could rigorously document the effect of HIV infection and subsequent treatment on multiple ageing markers, including telomere length, epigenetic ageing, and now proteomic ageing. In every case, uncontrolled HIV infection correlated with increased ageing rates, while ART substantially mitigated this effect.
The PAC specifically gauges alterations in inflammatory signaling and drug metabolism pathways, crucial axes affected by HIV. Compared with the group’s former epigenetic ageing clock (EAC), which quantifies DNA methylation changes, the PAC detects more immediate immune changes. During untreated infection, proteomic age increased rapidly, but once ART suppressed viraemia, proteomic age declined swiftly—showing its sensitivity to short-term immune modulation.
Intriguingly, the reversal of proteomic age acceleration was largely independent of classical markers of immune system recovery, such as CD4+ and CD8+ T-cell counts. This dissociation suggests that the biological recovery reflects more pervasive remodeling of inflammatory and innate immune pathways beyond T-cell quantity restoration alone. Thus, ART’s benefits encompass broader immunological recalibration beyond simply restoring adaptive immune populations.
These insights align with the prevailing medical guidance advocating early initiation and consistent adherence to ART immediately after HIV diagnosis. Dr. Ryan emphasized that despite careful clinical monitoring of T-cell parameters pre-ART, accelerated ageing was already evident near diagnosis, emphasizing the broad systemic impact of HIV beyond standard immune biomarkers and the critical window for intervention.
Acknowledging the study’s implications, the authors call for further validation of the plasma proteomic ageing clock across diverse global populations, particularly given genetic and environmental differences that may influence ageing biology. They also highlight the need for proteome-wide studies to pinpoint exact molecular pathways driving accelerated ageing in HIV, which could open new therapeutic avenues.
In summary, this research provides compelling evidence that effective antiretroviral therapy markedly reverses HIV-induced biological ageing, as measured by proteomic biomarkers. By integrating proteomics and longitudinal clinical data, the study deepens understanding of HIV pathogenesis and offers a valuable tool for evaluating biological ageing and disease progression in PWH, promising enhanced healthcare strategies for this population worldwide.
Subject of Research:
The impact of antiretroviral therapy on reversing accelerated biological ageing in people with HIV, measured using a novel plasma proteomic ageing clock.
Article Title:
Antiretroviral Therapy Reverses Accelerated Biological Ageing in HIV, Reveals New Proteomic Clock
News Publication Date:
Monday, 20 April 2026
Web References:
www.escmid.org/
References:
1. Ryan, B., Oumelloul, M.A., Rouached, S., et al. (2026). A plasma proteomic aging clock reflects reversal of accelerated aging in people with HIV under antiretroviral therapy. Oral presentation. ESCMID Global 2026.
2. Nasi M., De Biasi S., Gibellini L., et al. (2016). Ageing and inflammation in patients with HIV infection. Clin Exp Immunol. 2017 Jan;187(1):44-52.
3. Martínez-Martín, P., Esteban-Cantos, A., Jurado, F., et al. (2025). Prognostic Value of Blood Epigenetic Biomarkers of Aging in Persons With Well-Controlled Human Immunodeficiency Virus (HIV-1) Infection. Clinical Infectious Diseases.
4. Schoepf, I.C., Esteban-Cantos, A., Thorball, C. et al. (2023). Epigenetic ageing accelerates before antiretroviral therapy and decelerates after viral suppression in people with HIV in Switzerland: a longitudinal study over 17 years. Lancet Healthy Longevity.
Image Credits:
ESCMID Global
Keywords:
HIV, antiretroviral therapy, biological ageing, plasma proteomics, accelerated ageing, immune remodeling, Swiss HIV Cohort Study, proteomic ageing clock, epigenetic ageing, viral suppression, inflammation, immune system
