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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, and remained significant in three epigenetic measures after controlling for T cell changes. No acceleration was seen in age- and time interval-matched HIV-uninfected controls. Changes in genome-wide co-methylation clusters were also significantly associated with initial HIV infection (p≤ 2.0 × 10⁻⁴). These longitudinal observations …