Abstract: Living with HIV infection is associated with early onset of aging-related chronic conditions, sometimes described as accelerated aging. Epigenetic DNA methylation (DNAm) patterns can evaluate acceleration of biologic age relative to chronologic age. The early impact of initial HIV infection on five DNAm measures was examined before and approximately 3 years after HIV infection in the same individuals (n=102). Significant epigenetic age acceleration (1.9-4.8 years median age acceleration, 17.6-fold median estimated telomere shortening, all p≤0.001) was observed from pre- to post-HIV infection, in contrast to no acceleration in age-matched persistently HIV-seronegative controls over matched time intervals. Three DNAm age acceleration measures remained significantly associated with initial HIV infection even after controlling for changes in T cell subsets. These longitudinal observations clearly demonstrate an early and substantial impact of HIV infection on the epigenetic aging process, and suggest a role for HIV itself in the earlier onset of clinical aging.