HIV Infection Causes Premature Aging

American investigators indicate that both chronic and recent HIV infection appear to lead to an average aging advancement of nearly 5 years, increasing expected mortality risk by 19%, when compared with healthy volunteers.

Whereas many patients with HIV can expect to live decades after contracting the infection due to advancements in combination antiretroviral therapy, physicians have reported signs that resemble premature aging among patients with the disease. Using a highly accurate biomarker, the researchers measured the level to which HIV infection ages individuals at the biological level.

“The medical issues in treating people with HIV have changed,” said co-corresponding author Howard Fox, MD, PhD, a Professor in the Department of Pharmacology and Experimental Neuroscience at the University of Nebraska Medical Center. “We’re no longer as worried about infections that come from being immunocompromised. Now we worry about diseases related to aging, like cardiovascular disease, neurocognitive impairment, and liver problems.”

For the study, Fox and colleagues first developed and validated epigenetic models of aging that are independent of blood cell composition. These models assess epigenetic changes in individuals’ cells—which affect the DNA but not the DNA sequence—that are passed from one cell generation to the next and influence how genes are expressed. The epigenetic change used as a biomarker in the study was methylation, the process by which small chemical groups are attached to DNA. Methylation of DNA can impact how genes get translated into proteins.

Published in the April 21, 2016 issue of Molecular Cell, the study also found that sustained infection seems to result in global deregulation of the methylome across more than 80,000 CpGs and specific hypomethylation of the region encoding the human leukocyte antigen locus. Additionally, the study team found that decreased HLA methylation was predictive of lower CD4/CD8 T cell ratio, thus linking molecular aging, epigenetic regulation, and HIV disease progression.

“What we’ve seen in previous studies is that as we age, methylation across the entire genome changes,” said co-corresponding author Trey Ideker, PhD, a Professor of Genetics in the Department of Medicine at the University of California San Diego. “Some people call it entropy or genetic drift. Although we’re not sure of the exact mechanism by which these epigenetic changes lead to symptoms of aging, it’s a trend that we can measure inside people’s cells.”

All 137 study participants were enrolled in the long-term CNS Antiretroviral Therapy Effects Research (CHARTER) study, which focused on monitoring HIV-infected patients taking combination antiretroviral therapy. Participants were otherwise healthy and compared with 44 HIV-negative control subjects. An independent group of 48 patients both with and without HIV was included to confirm the findings.

“We set out to look at the effects of HIV infection on methylation, and I was surprised that we found such a strong aging effect,” said Ideker.

Adding to Ideker’s sentiments, Fox said, “Another thing that was surprising was that there was no difference between the methylation patterns in those people who were recently infected [less than five years] and those with chronic infection [more than 12 years].”

Whereas the study authors said medications could be developed in time to target the epigenetic changes they observed in the study, in the meantime, patients with HIV should be informed that they are at increased risk for age-related diseases but that these risks can be limited through healthy lifestyle choices in regard to exercise and diet, as well as drug, alcohol, and tobacco use.