Impact of sex differences in adult and paediatric HIV-1 cure

Stronger type I interferon responses in females compared to males, starting from intrauterine life, underpin the sex differences observed in HIV-1 cure/remission outcomes in children and adults. In adults these innate immune sex differences favour females achieving HIV-1 cure/remission over males. Recent studies of the adult viral reservoir reflect the ability of innate immune responses in females, including natural killer (NK) cell activity, to remove cells harbouring intact proviral DNA more effectively than males. In children, the situation is more complex. Initially, in the first years of life, males have a higher propensity to achieve HIV-1 cure/remission, at this stage benefiting from the effects of having weaker interferon (IFN)-I responses, including low baseline HIV-1 DNA loads and being recipients of an IFN-I sensitive transmitted founder virus. By mid-childhood, the picture is mixed, with the impact of stronger innate immunity in females combined with the development of more effective HIV-specific CD8 + T-cell response via immune ontogeny tending to favour females beyond the age of 5-10 years. In children, therefore, the double-edged sword effects of IFN-I in the setting of vertical transmission and immune ontogeny results in distinct, dynamic sex advantages through childhood.