While antiretroviral treatment (ART) reduced the acceleration of epigenetic age in PLWH, it didn’t bring it down to the level of HIV-negative controls, a small study published in The Lancet HIV showed.
European researchers analyzed DNA methylation in blood samples from 168 PLWH before they started treatment and again two years later, as well as samples from 44 HIV-negative controls that were matched based on chronological age and sex. Four estimators were used, two of which—PhenoAge and GrimAge—are relatively new, and better predict mortality and morbidities in the general population, compared to the older tools, Hannum and Horvath.
Prior to starting ART, epigenetic age acceleration was greater among PLWH than their HIV-negative counterparts, with the average increase varying widely by test (1.4 years with Hannum, 2.5 years with Horvath, 2.8 years with GrimAge, and 7.3 years with PhenoAge). After two years on antiretrovirals, the newer estimators still showed greater epigenetic age in PLWH than in HIV-negative participants, while the conventional ones found no difference between the two groups.
Aging was particularly accelerated in participants who had poor HIV lab values at baseline (i.e., a CD4 count below 200 cells/µL or a viral load over 100,000 copies/mL) compared to all PLWH. That said, in addition to slowing down biological aging, ART was particularly good at reducing proinflammatory leucocytes in those with worse baseline HIV labs, the researchers found.
Limitations included the study’s small size, the fact that most participants were young European men, the limited extent of matching with the control group, the lack of adjustment for confounders (such as lifestyle or socioeconomic characteristics), and the surfeit of information on comorbidities that are known to be more common among PLWH.
The clinical implications of the findings are unclear, but epigenetic aging estimators might be able to identify PLWH at higher risk of aging-related comorbidities, which could facilitate targeted prevention, study authors concluded.
ART can be a two-edged sword for biological aging, since some antiretrovirals are associated with aging-related comorbidities, Jacqueline Capeau of Sorbonne University in Paris, France, warned in a commentary. Determining epigenetic age on an individual basis may not be helpful in clinical practice, she opined; instead, it could have more use in studies, especially among older PLWH.