HIV Treatment Reduces Accelerated Biological Aging by Nearly Four Years
Antiretroviral therapy can partially reverse accelerated biological aging in people with HIV.
Advances in antiretroviral therapy (ART) have transformed HIV from a life‑threatening infection into a manageable chronic condition—but questions remain about how effectively treatment mitigates long‑term biological damage.
Growing evidence suggests that people with HIV experience accelerated biological aging, driven by chronic inflammation and immune dysregulation, contributing to elevated risks of cardiovascular and other age‑related diseases.
At ESCMID Global 2026, researchers presented new data showing that ART can partially reverse this accelerated aging at the molecular level, reducing biological age by nearly four years.
The findings come from a proteomics study led by Dr. Barry Ryan, a postdoctoral researcher at École Polytechnique Fédérale de Lausanne, who has previously published work on telomere attrition and epigenetic aging in HIV.
By developing and applying a plasma proteomic aging clock (PAC) within the Swiss HIV Cohort Study, Ryan and colleagues revealed the dynamic biological recovery that follows viral suppression.
Technology Networks spoke with Ryan to talk about how his work raises important questions about how aging is measured in HIV, how clinicians assess long‑term risk, and what biological recovery really looks like beneath standard immune markers.
PACs capture distinct layers of aging biology
What makes a PAC different from more established aging measures like epigenetic clocks or telomere length?
Biological aging is a multifaceted process that unfolds across multiple molecular layers, from chromosomal integrity to gene regulation and protein signaling.
PACs differ fundamentally from epigenetic clocks or telomere length because they measure aging at the level of circulating proteins, which are downstream effectors of cellular and systemic physiology. As Ryan explained, these clocks capture a different “layer” of biology, one that reflects active inflammatory signaling, metabolic processes, and immune responses rather than inherited or epigenetically programmed changes.
While overlap between aging measures is expected—particularly for broad effects such as chronic disease or inflammation—the proteome offers complementary insights.
“One specific potential advantage of PACs is that they could be reconstructed using relatively small, targeted protein panels that may be cheaper and simpler to measure than genome-wide assays,” said Ryan.
The team found that the PAC responded more rapidly to changes in disease state than their previously published epigenetic aging clock. This sensitivity allowed them to capture sharp increases in biological age during untreated HIV infection and equally rapid declines following viral suppression.
How proteomic aging measures differ:
- Reflects dynamic inflammatory and metabolic signaling rather than static genomic features.
- Captures complementary biological information alongside epigenetic and telomere clocks.
- Demonstrates higher sensitivity to short‑term disease and treatment effects.
Untreated HIV drives dramatic age acceleration that ART can reverse
What did you observe about biological aging during untreated HIV infection and after the introduction of ART?
By applying the PAC to longitudinal samples spanning untreated and treated infection, the researchers observed biological age acceleration during viremic HIV infection. At the time points closest to HIV diagnosis, participants showed a median increase of ~10 years in proteomic age relative to their chronological age, despite being closely monitored and not yet showing severe clinical deterioration.
Following the initiation of ART and successful suppression of HIV viremia, the accelerated aging was significantly reduced. Within a median of 1.55 years of treatment, participants experienced an average reversal of 3.7 years in proteomic age, with longer ART exposure driving trajectories closer to normal chronological aging. The recovery was not transient; proteomic age continued to improve with sustained viral suppression.
“By performing a mediation analysis, we showed that changes in proteomic advanced age were not driven by T-cell counts; therefore, our results suggest that advanced proteomic aging and its reversal under ART reflect more than immune reconstitution,” said Ryan.
HIV infection and aging trajectories:
- Untreated HIV accelerates biological aging by roughly a decade.
- ART leads to rapid and sustained reductions in proteomic age.
- Age reversal occurs independently of T‑cell recovery.
Rethinking long-term risk monitoring beyond T-cell counts
How might proteomic aging help clinicians think differently about monitoring long-term health risks in people living with HIV?
Clinicians recognize that immune cell counts alone do not fully predict long‑term outcomes in people living with HIV. Despite effective viral suppression and apparent immune reconstitution, many patients continue to develop cardiovascular disease and other age‑associated conditions at higher rates than the general population.
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“Our PAC captured changes in advanced age that were driven by inflammation and HIV viraemia suppression, but not by these immune cell counts,” said Ryan.
The findings suggest that aging‑related risk in HIV reflects systemic inflammatory burden rather than immune cell numbers alone.
“A proteomic aging clock could therefore be considered a complementary summary measure for monitoring long-term health risk in people with HIV.” — Dr. Barry Ryan.
However, Ryan emphasized caution. While PACs show promise as complementary tools, extensive validation across cohorts and platforms would be required before clinical implementation.
Proteomic aging in clinical risk assessment:
- Captures inflammatory and metabolic risk not reflected by T‑cell counts.
- Offers a potential complementary measure of long‑term health risk.
- Requires robust external validation before clinical use.
Integrating proteomic, epigenetic, and telomere clocks to understand HIV aging
How do your proteomic findings fit alongside your previous work on epigenetic and telomere aging, and what are the key next steps?
Taken together, the proteomic, epigenetic, and telomere studies present a consistent narrative: untreated HIV accelerates aging across multiple biological layers, while early and sustained ART slows—or partially reverses—this process.
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“In this study, we have extended these findings to the proteome,” added Ryan.
However, Ryan acknowledged limitations in his work. The PAC was trained specifically in people with HIV who were virologically suppressed, which may limit generalizability.
“The natural next step would be to replicate the analysis using a PAC developed in a healthy cohort and compare results across clocks,” he added.
“Currently, this is challenging due to PACs showing limited generalizability across studies because of differences in proteomic platforms, preprocessing pipelines, participant characteristics, statistical methods, and the tissue or cell types sampled,” said Ryan.
Looking ahead, pathway‑level analyses will be essential to identify the specific biological mechanisms driving aging acceleration and recovery in HIV.
Next steps in HIV aging research:
- Aligns proteomic findings with epigenetic and telomere aging evidence.
- Highlights the limits of immune reconstitution as a recovery marker.
- Calls for cross‑cohort validation and pathway‑level mechanistic studies.
The study, presented at ESCMID Global 2026, demonstrated that ART can significantly reverse accelerated biological aging in people with HIV, reducing proteomic age by nearly four years. Using a novel plasma PAC, researchers showed that untreated HIV dramatically accelerates aging, while sustained viral suppression promotes ongoing biological recovery. Importantly, these changes occur independently of traditional immune markers, underscoring the role of systemic inflammation in HIV‑related aging.
Key takeaways
- Untreated HIV accelerates biological aging by approximately 10 years.
- ART significantly reverses this effect, with continued improvement over time.
- Proteomic aging reflects inflammatory recovery beyond T‑cell reconstitution.
- Further validation is needed before proteomic clocks enter clinical practice.
This content includes text that has been created with the assistance of generative AI and has undergone editorial review before publishing. Technology Networks' AI policy can be found here.
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