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It is recommended that HIV-infected individuals receive annual influenza vaccination due to their high susceptibility to influenza infection, especially among women. However, there have been few studies investigating sex-related responses to influenza vaccine in antiretroviral therapy (ART)-treated HIV-infected individuals.In this study, 26 aviremic ART-treated HIV-infected individuals and 16 healthy controls were enrolled in the current study. Blood was collected prior to vaccination (D0), on days 7–10 (D7) and on days 14–21 (D14) following administration of the 2013–2014 seasonal influenza vaccine. A series of analyses evaluated the serological and cellular responses following influenza vaccination.Female HIV-infected individuals had increased influenza-specific antibody avidity relative to male HIV-infected individuals, but similar plasma levels of influenza-specific binding antibodies and neutralizing antibodies. Increased cycling B cells and follicular helper CD4+ T (Tfh) cells were observed in female HIV-infected individuals pre and postvaccination compared with male HIV-infected individuals, and cycling Tfh cells were directly correlated with influenza-specific antibody avidity. Moreover, plasma testosterone levels were inversely correlated with antibody avidity index. The magnitude of microbial translocation [plasma lipopolysaccharide (LPS)] level was directly correlated with influenza-specific antibody avidity. Circulating 16S rDNA microbiome showed that enrichment of specific species within Proteobacteria was associated with influenza-specific antibody avidity. These results, including differences based on sex and correlations, were only observed in HIV-infected individuals but not in the healthy controls.This study demonstrated sex differences in influenza-specific antibody avidity in ART-treated HIV disease, and provides valuable information on vaccination strategy in the ART-treated HIV-infected population.