Antiretroviral Therapy Reduces Biological Aging in HIV Patients by Nearly Four Years, Study Finds
Researchers at ESCMID Global 2026 in Munich on Monday reported that antiretroviral therapy reduced biological aging in people with HIV by nearly four years. According to the study, the therapy slowed accelerated aging caused by untreated HIV, as measured by the Proteomic Age Clock, indicating ongoing biological recovery with sustained treatment.
Using the Proteomic Age Clock (PAC), a tool that estimates biological age based on plasma proteomics, the study showed that untreated HIV infection accelerates biological age by a median of 10 years. After a median of 1.55 years on ART, participants demonstrated a statistically significant reduction in proteomic age, indicating ongoing biological recovery with sustained treatment, the researchers said.
The study presented Monday at ESCMID Global 2026 in Munich found that antiretroviral therapy (ART) reduced accelerated biological aging in people with HIV by an average of 3.7 years, with a 95% confidence interval of 2.7 to 4.7 years and a p-value of 0.0001, according to researchers.
The PAC measurements revealed that biological age moved closer to chronological age with longer ART exposure. The researchers noted that accelerated proteomic age correlates with DNA methylation age, comorbidities, and mortality in people with HIV, underscoring the clinical relevance of these findings. The study authors emphasized that uncontrolled HIV infection is linked to faster aging and that ART significantly slows this process.
Previous research has documented epigenetic age acceleration in untreated HIV patients, with mean increases ranging from 1.4 to 7.3 years depending on the epigenetic clock used. For example, the Horvath clock showed a mean acceleration of 2.5 years, while the PhenoAge clock indicated 7.3 years of accelerated aging. Studies have also shown partial reversal of epigenetic age acceleration after ART initiation, with one study reporting a reduction of 0.6 years in GrimAge acceleration after two years of therapy, though biological age remained higher than in HIV-negative controls. These findings were reported in studies published before and during 2026, including the NEAT trial results published in The Lancet HIV in May 2021.
Mechanistically, ART slows aging linked to uncontrolled HIV by improving immune function. Effective suppressive ART increases CD4 T-cell counts and reduces viremia, which lowers frailty risk, according to prior studies. ART also reduces exhausted and senescent T cells and improves naïve-to-memory T cell ratios. Additionally, ART enhances interferon-gamma production by CD4+ T cells and diminishes HIV-specific CD8+ T cell responses. Some antiretroviral drugs have been associated with reductions in age acceleration, while the size of the HIV reservoir correlates with biological aging markers, according to a February 2026 study published in Nature Communications.
Clinically, these findings could transform how HIV treatment and long-term health outcomes are monitored. Researchers suggested that ART alone is sufficient to control HIV and restore cellular functions related to aging. Mendelian randomization analyses cited in the Nature Communications study demonstrated causality between organ aging and inflammatory and metabolic complications in people with HIV, highlighting potential targets for improving health span. These data also challenge the hypothesis that premature aging persists despite long-term immune reconstitution with ART.
The ESCMID Global 2026 presentation took place on April 20 in Munich, Germany. The study adds to a growing body of evidence that supports the role of ART in mitigating premature biological aging in people with HIV. Previous trials, such as the NEAT trial, found no difference between ART regimens in reversing aging markers, and frailty associated with HIV has been shown to be transient and lessened over time with treatment. Epigenetic clock analyses continue to indicate partial reversal of accelerated aging after two years of ART, though biological age often remains elevated compared to HIV-negative individuals.
