Accelerated aging in HIV: The role of ART, early testing, and comorbidities

HIV significantly accelerates the aging process within three years of seroconversion and could even shave years off the lifespan of people living with HIV (PLWH), according to a recent study published in the peer-reviewed journal iScience. This study is the latest in a growing body of research suggesting that PLWH, whether on effective therapy or not, age at a faster rate than people without HIV (PWoH). And while antiretroviral therapy saves lives, it doesn’t prevent PLWH from experiencing age-related disorders—including heart disease, kidney disease, and cognitive problems—sooner than PWoH.

The 102 study participants were drawn from the ongoing Multicenter AIDS Cohort Study (MACS). Researchers analyzed their blood twice: six months or less before they acquired HIV, and again between two to three years after seroconversion. Comparing these samples with 102 PWoH of the same ages, researchers examined five epigenetic measures of aging: Age Acceleration Residual (AAR), which captures epigenetic age acceleration; Extrinsic Epigenetic Age Acceleration (EEAA), which captures intrinsic methylation changes and extrinsic blood cell composition changes; Phenotypic Epigenetic Age Acceleration (PEAA) and Grim Epigenetic Age Acceleration (GEAA), which are measures of mortality risk; and DNA methylation–based estimates of telomere length, which shorten with increasing age. The goal was to estimate whether biological age deviated from chronological age in any of these measures for seroconverted participants compared with their seronegative counterparts.

The team reported that PLWH showed “significant” age acceleration of 2 to 5 years post-seroconversion in all four epigenetic clock measurements, as well as more rapid shortening of telomeres, in PLWH compared with PWoH.

This study had several limitations. Because MACS studies only men, all participants in this study were men—and only a small number were non-white participants. And although some participants were on antiretroviral therapy (ART), the sample size overall was too small to consider how ART might impact the cellular aging process.

Could ART Reverse Cellular Aging?

The reason for accelerated aging at the cellular level for PLWH—whether chronic inflammation, the reduction of T cells before a person goes on ART, or both—is unclear, according to the study’s lead author Elizabeth Crabb Breen, Ph.D., a professor emerita at the UCLA Cousins Center for Psychoneuroimmunology and of psychiatry and behavioral sciences at the David Geffen School of Medicine at UCLA.

Two previously published papers by members of Breen’s team provide additional insight into the effect of ART on cellular aging. One study concluded that ART partially reduces the degree of acceleration of four levels of biological aging, but not to baseline levels for two of them, AAR and EEAA. The second, a longitudinal analysis comparing epigenetic aging between untreated PLWH and PLWoH, concluded that HIV leads to a twofold greater rate of epigenetic aging, which accelerates over time.

Breen and colleagues are preparing to publish findings from a new study that suggests that the epigenetics of PLWH at the time they go on ART may determine where they are after starting treatment, which would underscore the importance of starting therapy as early as possible.

“We’re seeing [in the newest study] that two years of antiretroviral therapy doesn’t restore epigenetics to the same age-appropriate patterns as [see in] uninfected peers,” Breen tells TheBodyPro. “There’s improvement, but [accelerated cellular aging] has not been completely remedied.”

Test and Treat Early for HIV, Monitor Comorbidities

The iScience study has several takeaways for clinicians, starting with the importance of getting PLWH on treatment fast, not only to stabilize T cells and allow viral suppression, but also to prevent cellular aging, Breen says.

“People need to know their HIV status and that requires being proactive about testing patients,” says Breen. “Clinicians need to help people get on a schedule of being tested for HIV, because about 13% of all people in the United States [who] have HIV don’t know their status. That can be as [many] as 156,000 people a year.”

Another lesson from the study is that clinicians may want to screen PLWH for comorbidities of aging (eg, osteoporosis, frailty, or liver disease) sooner than they would PWoH and be prepared to intervene if these issues are showing up. “Don’t just go based on age charts; you have to go based on HIV as well,” says Breen.

Senior author Beth Jamieson, Ph.D., professor of medicine in the division of hematology/oncology at the David Geffen School of Medicine at UCLA, says the study refutes an attitude she often encounters, which is that contracting HIV is no big deal when there is effective therapy.

“There is substantial damage being done very early in infection, and so far, our data suggest that even antiretroviral therapy can’t completely overcome that,” Jamieson tells TheBodyPro. “Everyone needs to be mindful that HIV is still a public health issue. Awareness, education, prevention, testing, and early treatment are still critically important.”

One of the next goals for Breen’s team is to better understand what aging really means at the cellular level and how genes affect specific age-related diseases.

“We might be able to use these genetic signatures to say, ‘Okay, this specific gene pathway is involved or that specific gene pathway is involved.’ And maybe we can develop some ways to have some early intervention, or use it as a prognostic marker [so] that if a person looks [to be] aging too quickly, we can start doing things that we know will help offset frailty or osteoporosis or other difficulties,” says Breen. “To me, that’s one of the really exciting aspects of [this]. It’s going to help us untangle aging in the context of HIV, but also perhaps even aging outside of HIV.”

By Larry Buhl