Is There Accelerated Aging for Those With Living With HIV?

After the successful introduction of highly active antiretroviral therapy (HAART) for the treatment of HIV/AIDS, clinical reports began to surface that people living with HIV, even those with suppressed viral loads, were developing some of the diseases associated with aging much younger than their peers who were living without HIV.

Those reports led a team of researchers led by Beth D. Jamieson, Ph.D., a professor at the David Geffen School of Medicine at UCLA, to set out to understand why that might be.

Beth D. Jamieson

In a study published recently in the journal iScience, Jamieson and her colleagues looked to see if HIV itself was accelerating aging and what, if any, role was HAART playing.

“One of the difficulties in attempting to address these questions is that the mechanisms underlying aging were even more poorly understood a decade ago than they are now and we still have a lot to learn,” Jamieson said. “It was the discovery and development of the original epigenetic clock by Steve Horvath that gave us a way to begin to address the relationship between the mechanisms that underlay HIV pathogenesis and the mechanisms of aging.”

So, the researchers reasoned that if they could understand the relationship between aging and HIV infection, they would increase the understanding not only of HIV pathogenesis, but, possibly, of aging.

“By better characterizing the mechanisms underlying the development of these comorbidities of aging with HIV, we may provide potential prognostic markers that can be used for prescribing earlier interventions, and ideally identify new targets for therapeutic intervention,” Jamieson said.

The study noted HIV can accelerate aging at the cellular level within just two to three years of initial infection.

“We don’t know all the factors that contribute to the changes in the epigenetic landscape after HIV infection, but clearly, a large contributor is the changes in the make-up of the cells of the immune system,” Jamieson said. “We didn’t look at all immune cell populations, just the T-cell subsets which we’d previously identified as being highly associated with the increase in biologic age in people living with HIV.”

The findings also suggest new HIV infection could shave almost five years off one’s lifespan.

“This is just a reflection that by increasing epigenetic age, it is likely that lifespan will therefore be shortened as several of the epigenetic clocks are not only associated with the diseases of aging, but are also prognostic markers for mortality,” Jamieson said. “This is consistent with an earlier published paper by Nik Wada who found that, after excluding AIDS related factors, lifespan in men enrolled in the Multi-Center AIDS Cohort (MACS) and on ART (antiretroviral therapy, still experienced a nine-year shorter life span than men in the MACS who were not living with HIV.”

For Jamieson, the most surprising finding was just how fast HIV infection made a significant change in the epigenetic landscape.

“Maybe, given how devastating it can be to the immune system, this shouldn’t have surprised me, but it did,” she said.

She also believes one of the biggest takeaways from the research is the myriad problems that come with HIV, and that despite what the media says about getting HIV as not being that big a deal anymore (You just take medication and get on with life!), it’s still vital to prevent new HIV infections.

“This study demonstrates very clearly that HIV itself can change the rate of epigenetic aging, increasing a person’s long-term risk for a shorter health span,” Jamieson said. “Last year we published that, once infected, people living with HIV continue to age at the epigenetic level at twice the rate of their peers living without HIV. When we combine these findings with our pilot study published in 2020 in which we found that two years of treatment did not restore a person’s epigenetic age to age-appropriate patterns, our findings suggest that just taking a drug and getting on with life is not going to be in the cards.”