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Well-established contributors include microbial translocation due to gut barrier impairment, residual viral replication in sanctuary sites, reactivation of latent co-infections (e.g., cytomegalovirus), and increased cellular senescence ( This review aims to synthesize current knowledge on how HIV/SIV infection and ART induce mtDNA damage and how this damage acts as a key indicator and mechanistic driver of associated immunometabolic changes