Sexual dimorphism in HIV-1 infection

Sex-specific differences affecting various aspects of HIV-1 infection have been reported, including differences in susceptibility to infection, course of HIV-1 disease, and establishment of viral reservoirs. Once infected, initial plasma levels of HIV-1 viremia in women are lower compared to men while the rates of progression to AIDS are similar. Factors contributing to these sex differences are poorly understood, and range from anatomical differences and differential expression of sex hormones to differences in immune responses, the microbiome and socio-economic discrepancies, all of which may impact HIV-1 acquisition and disease progression. Ongoing research efforts aiming at controlling HIV-1 disease or reducing viral reservoirs need to take these sex-based differences in HIV-1 pathogenesis into account. In this review, we discuss established knowledge and recent findings on immune pathways leading to sex differences in HIV-1 disease manifestations, with focus on HIV-1 latency and the effect of female sex hormones on HIV-1.