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Immunological analyses performed in healthy adolescents born of HIV-infected (seroreverters) or healthy mothers (healthy controls; HC) showed that immune activation and a skewing of postthymic differentiation are present in adolescent seroreverters. In-utero HIV exposure results in long-lasting imprinting on the immune system. Alternatively, an immune response naturally more prone to activation could prevent vertical infection. Endogenous antivirals (APOBEC, TRIM5α) were comparable in seroreverters and HC, and might not play a role in resistance to vertical HIV infection.