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Aging Begins at Time of HIV Infection, Frailty in PWH
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the study reported here is the largest, and the first with matched HIV-uninfected controls, to longitudinally follow individuals over the course of becoming infected with HIV, and to document epigenetic changes consistent with accelerated biological aging.
Over a relatively short time frame (less than three years on average), during which age-matched HIV-uninfected men showed no significant changes or acceleration in any epigenetic measure of aging, men who became infected with HIV showed highly significant age acceleration in three out of four of the epigenetic clocks as well as accelerated estimated telomere shortening (Figure 2).
This clearly demonstrates an early and substantial impact of HIV infection on the epigenetic aging process, which begins in the first months and years of living with HIV and is temporally associated with changes in a variety of T cell subsets.
When the numbers or percentages of the T cell subsets in each model were taken into account, EEAA, PEAA, and aaDNAmTL, which had remained significantly associated with initial HIV infection when controlling for demographic and other clinical factors, were very clearly no longer significant (study visit∗HIV serostatus group, all p values > 0.43; Tables 4 and S10). Therefore, the changes in critical T cell numbers and percentages are strong contributors to the epigenetic changes observed and may explain how initial HIV infection is driving accelerated biologic aging characterized by these particular epigenetic measures.
Highlights
• Accelerated epigenetic aging begins within three years after initial HIV infection
• No epigenetic aging was observed in age-matched men over the same time period
• Epigenetic and T cell changes after HIV infection were temporally associated
• Initial HIV infection is associated with significant genomic methylation changes
Summary
Living with HIV infection is associated with early onset of aging-related chronic conditions, sometimes described as accelerated aging. Epigenetic DNA methylation patterns can evaluate acceleration of biological age relative to chronological age. The impact of initial HIV infection on five epigenetic measures of aging was examined before and approximately 3 years after HIV infection in the same individuals (n=102). Significant epigenetic age acceleration (median 1.9-4.8 years) and estimated telomere length shortening (all p≤ 0.001) were observed from pre-to post-HIV infection, while no acceleration was seen in age- and time interval-matched HIV-uninfected controls.
Epigenetic changes were temporally associated with changes in T cell subsets. Changes in genome-wide co-methylation clusters were also significantly associated with initial HIV infection (p≤ 2.0 x 10-4). These longitudinal observations clearly demonstrate an early and substantial impact of HIV infection on the epigenetic aging process, and suggest a role for HIV in the earlier onset of clinical aging.
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