DNA May Age More Quickly in Patients With Cancer Who Are HIV-positive

Changes in DNA methylation may lead to accelerated aging in patients with cancer and HIV.

Patients with cancer who are living with HIV may have an older epigenetic age than patients with cancer who do not have HIV, according to Anna Coghill, PhD, MPH, of the Moffitt Cancer Center, in a presentation at the AACR Special Conference: Aging and Cancer. Coghill explained that the data showed an average biological age that is 4.5 years older among patients with cancer who are HIV positive than patients with cancer without HIV.

“Patients with HIV may have DNA that appears older than their chronologic age,” said Coghill. “Our results show that patients with HIV may be biologically older than those without HIV, which could impact how their tumors respond to treatment.”

Additionally, signs of aging may be worse in cancer patients who are HIV-positive from long-term immune activation, inflammation, or metabolic changes because of HIV infection, explained Coghill in a press release. Although patients with HIV now have access to antiretroviral therapies, they still have worse clinical outcomes following cancer diagnoses, along with an increased susceptibility to developing cancer and other diseases that are related to age. Among non-AIDS death in people with HIV, cancer is the leading cause of mortality.

“An important focus of the field is identifying molecular features that could explain the poorer treatment responses in patients with HIV,” Coghill said in the press release.

Furthermore, Coghill explained that epigenetic age is slightly different than chronological age. Specifically, epigenetic age is a type of biological age that is defined by DNA methylation patterns, which is based on patterns of methylation that accumulate on DNA over time, Coghill noted.

Coghill and colleagues hypothesized that epigenetic aging would be worse for patients with cancer who also had HIV infection and put their idea to the test in a recent trial. The study compared the epigenetic ages of 65 patients with HIV (no acquired immunodeficiency syndrome (AIDS)-defining solid tumor), to patients without HIV.

Using DNA methylation sequencing on tumor samples, researchers tested the epigenetic age and immune cell composition of the tumors. Among participants, the tumor types were similar in both arms, as were treatment status and chronological age.

Two algorithms (epiTOC2 and GrimAge) were then used to determine the epigenetic age. The data showed that HIV-positive patients had cell division rates that were 70% more than patients without HIV. Additionally, the tumors of HIV-positive patients had lower levels of immune cells including neutrophilis and CD4+ T cells, but higher levels of CD8+ T cells.

While this study includes a limited sample size for certain cancer types, other studies, led by Coghill, are including individuals in their research who have diverse epigenetic ages to see if this can impact clinical outcomes.

“We hope that understanding why patients with HIV have worse outcomes to cancer therapy will serve as an initial step towards reducing this disparity,” Coghill said in the press release.

Reference

American Association for Cancer Research. HIV-positive Patients with Cancer May Have Accelerated Biological Aging. AACR Special Conference: Aging and Cancer. November 17, 2022.