HIV-specific CD8⁺ lymphocytes in semen are not associated with reduced HIV shedding

Sexual contact with HIV-infected semen is a major driving force behind the global HIV pandemic. Little is known regarding the immune correlates of virus shedding in this compartment, although HIV-1-specific CD8⁺ T cells are present in semen. We collected blood and semen from 27 chronically HIV-infected, therapy-naive men without common sexually transmitted infections or urethral inflammation and measured HIV-1 RNA viral load and cytokine/chemokine levels in both compartments. HIV-1 RNA levels were 10-fold higher in blood than semen, but discordantly high semen shedding was associated with higher semen levels of the proinflammatory cytokines IL-6, IL-8, IL-12, and IFN-γ. Virus-specific CD8⁺ T cell epitopes were mapped in blood by IFN-γ ELISPOT, using an overlapping HIV-1 clade B peptide matrix, and blood and semen CD8⁺ T cell responses were then assayed ex vivo using intracellular IFN-γ staining. HIV-specific CD8⁺ responses were detected in 70% of semen samples, and their frequency was similar to or higher than blood. There was no correlation between the presence of virus-specific CD8⁺ T cells in semen and levels of HIV-1 RNA shedding. Among participants with detectable CD8⁺ IFN-γ semen responses, their relative frequency was not associated with reduced HIV-1 RNA shedding, and their absolute number was correlated with higher levels of HIV-1 RNA semen shedding (r = 0.6; p = 0.03) and of several proinflammatory cytokines. Neither the presence nor the frequency of semen HIV-specific CD8⁺ T cell IFN-γ responses in semen correlated with reduced levels of HIV RNA in semen.