A major study presented today at ESCMID Global 2026 found that antiretroviral therapy (ART) reduces accelerated biological aging by nearly four years in people living with HIV (PWH). This discovery could change the way clinicians monitor HIV treatment and long-term health outcomes.
Researchers have developed the Plasma Proteomic Aging Clock (PAC), a tool that uses patterns across hundreds of blood proteins to estimate biological age, reflecting physiological aging rather than chronological age. This model was applied to participants in the Swiss HIV Cohort Study (SHCS).
PAC was trained on 941 plasma samples from PWH undergoing successful ART and subsequently evaluated in an independent cohort of 80 participants who provided 294 longitudinal samples spanning the viremic pre-ART infection (when HIV was detected in the blood) and suppressive post-ART stages.
During untreated HIV infection, PAC estimated that participants’ biological age accelerated by a median of 10 years. After a median duration of 1.55 years on ART, researchers observed a statistically significant mean decrease in proteomic age of 3.7 years (95% CI 2.7 to 4.7; p = 0.0001 – see Figure 1). Trajectory analysis showed that proteomic age continued to approach chronological age with increasing duration of ART exposure, suggesting that biological recovery progresses with continued treatment.
Previous studies have suggested that biological aging may be accelerated in PWH, which is associated with an increased risk of age-related conditions such as chronic inflammation and coronary artery disease, highlighting the clinical urgency of these findings.
This study demonstrates the importance of early initiation and optimal adherence to ART. We are very fortunate to have a unique group of SHCS who collected samples for up to 8 years before starting ART. This group measured the effects of untreated HIV infection and successful ART on telomere shortening, epigenetic aging, and now proteomic aging. In both cases, we showed that uncontrolled HIV infection is associated with accelerated aging, and ART significantly slows this down. ”
Dr. Barry Ryan, Principal Study Author, Postdoctoral Researcher at EPFL (Switzerland)
PAC primarily captures changes in inflammatory signaling and drug metabolic pathways. When compared with the research team’s previously published epigenetic aging clock (EAC) in the same cohort, both clocks showed similar overall trends. However, PAC was more sensitive to short-term immune changes, showing a more rapid increase during untreated infection and a more rapid decline when suppressed by ART once HIV in the blood became detectable (viremia).
Importantly, the reversal of proteomic age acceleration after ART was not significantly associated with recovery of CD4+ or CD8+ T cell numbers, suggesting that this reversal reflects broader inflammatory and innate immune remodeling rather than T cell reconstitution alone.
“Our findings support the current consensus to start ART promptly after HIV diagnosis,” Dr. Ryan explained. “Participants underwent close monitoring including CD4 and CD8 T-cell counts before ART. Nevertheless, accelerated proteomic aging was observed independent of T-cell homeostasis, with acceleration already occurring at the time closest to HIV diagnosis.”
The authors call for external validation of PAC in more diverse global populations and proteome-wide feature attribution studies to pinpoint specific pathways driving HIV-related aging biology.
“While the specific pathways of recovery may vary by ancestry and population, the global trend of accelerated aging due to untreated HIV and attenuated HIV after viral suppression is likely to generalize,” Dr. Ryan added.
sauce:
European Society of Clinical Microbiology and Infectious Diseases
