A groundbreaking study has illuminated how Human Immunodeficiency Virus (HIV) infection hastens biological aging processes, yet effective treatment with antiretroviral therapy (ART) can significantly counteract this effect. Researchers developed a novel plasma proteomic aging clock (PAC), a tool that analyzes patterns in hundreds of blood proteins to gauge physiological age rather than mere chronological years. In untreated individuals, HIV propelled biological age forward by a median of 10 years, but after roughly 1.5 years on ART, proteomic age dropped by an average 3.7 years, with further improvements over time.

This discovery, highlighted prominently by the University of Minnesota's Center for Infectious Disease Research and Policy (CIDRAP), underscores the transformative potential of timely ART initiation. As people living with HIV (PLWH) increasingly reach older ages, understanding these dynamics becomes crucial for long-term health management and public health strategies in the United States.

The Science Behind the Proteomic Aging Clock

The PAC represents a leap in aging assessment technology. Traditional clocks, like epigenetic ones measuring DNA methylation, have shown HIV links to accelerated aging, but the PAC offers heightened sensitivity to short-term shifts, particularly inflammation-related changes. Trained on 941 plasma samples from PLWH on successful ART, it was validated using 294 longitudinal samples from 80 Swiss HIV Cohort Study (SHCS) participants—spanning pre-ART viremia to post-ART suppression.

Key proteins captured inflammatory signaling and drug metabolism pathways. Untreated HIV spiked proteomic age rapidly; ART suppression reversed it swiftly, independent of CD4 T-cell recovery, pointing to innate immune remodeling.

Lead researcher Dr. Barry Ryan from EPFL noted, "Uncontrolled HIV links to faster aging across telomere shortening, epigenetic, and now proteomic measures—ART slows it markedly."

Mechanisms Driving HIV's Aging Acceleration

HIV fuels premature aging via persistent immune activation and chronic inflammation, even at low viral loads. The virus triggers ongoing cytokine release—interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)—mimicking age-related inflammaging. Mitochondrial dysfunction, oxidative stress, and gut microbiome dysbiosis compound this, hastening cellular senescence.

Studies confirm epigenetic age acceleration of 4.8-7.4 years post-seroconversion. Viral reservoirs evade ART, sustaining subtle inflammation. Coinfections like hepatitis C amplify risks, alongside lifestyle factors: smoking prevalent among PLWH triples cardiovascular odds.

ART's Protective Role: Evidence from Longitudinal Data

ART suppresses viremia, slashing inflammation markers by 30-50%. The PAC study revealed proteomic age converging toward chronological norms with prolonged therapy, suggesting reversibility. Earlier epigenetic clocks showed partial reversal post-ART, but PAC's proteome focus detects quicker innate immune shifts.

In SHCS, post-1.55 years ART (median), age gap narrowed 3.7 years (p=0.0001). Longer exposure yielded sustained gains. Dr. Ryan emphasized, "Early ART start and adherence are vital—global trends likely generalize." For details, see the preprint abstract.

Photo by Nasjere Williams on Unsplash

Aging HIV Population in the United States

Over half of ~1.2 million US PLWH are 50+, projected to reach 70% by 2030. By 2040, median age shifts 11 years older. Non-AIDS conditions—heart disease, neurocognitive impairment, frailty—dominate morbidity, costing billions annually.

ART adherence hovers 62-83%, vital as lapses accelerate aging. Urban/rural disparities persist; older PLWH face polypharmacy, isolation. More at HIV.gov aging resources.

Challenges and Comorbidities in PLWH

• Cardiovascular Disease: 2-4x risk, inflammation-driven atherosclerosis.
• Neurocognitive Decline: HIV-associated neurocognitive disorder (HAND) in 50% over 50.
• Frailty: Accelerates 2x faster; sarcopenia, osteoporosis prevalent.
• Cancers: Non-AIDS-defining like lung, anal rise 2-7x.
• Mental Health: Depression doubles, stigma compounds.

Multimorbidity burdens healthcare; integrated geriatric-HIV models emerging.

University of Minnesota's Role in HIV Research

UMN's CIDRAP, a global leader, amplified this study, reflecting its commitment to translating research. UMN Medical School advances HIV cures, cell transmission blocks ($3.1M grant). Faculty explore inflammaging, proteomics in PLWH lungs.

Higher ed fosters interdisciplinary teams—virology, gerontology, bioinformatics—training next-gen researchers. Programs like UMN's HIV Medicine equip clinicians for aging cohorts.

Clinical Implications and Lifestyle Synergies

Prioritize immediate ART post-diagnosis; monitor proteomic/epigenetic clocks routinely? Combine with statins, exercise reducing inflammation 20-30%. Smoking cessation, Mediterranean diet vital—cut CVD 30%.

Telehealth boosts adherence in rural US; peer support combats isolation. For PLWH over 50, frailty screens, deprescribing optimize outcomes.

Photo by Huichao Ji on Unsplash

Future Research Directions

Longitudinal PAC validation across ancestries; combine clocks for precision. Reservoir-targeting therapies? Long-acting ART adherence trials. Universities lead: UMN, EPFL collaborations globalize insights.

Explore senolytics reversing senescence; microbiome interventions. By 2030, aging PLWH demand innovative trials.

Actionable Insights for Healthcare Providers and PLWH

For Providers: Screen comorbidities early; promote adherence apps. Multidisciplinary clinics.

For PLWH: Daily ART, exercise 150min/week, quit smoking. Annual frailty assessments.

Optimism: ART plus lifestyle yields healthy longevity. Explore CIDRAP for updates: CIDRAP article.