OA04.03
Background: Studies of individuals who appear to resist HIV infection, such as HIV- partners in HIV discordant relationships, are important for identifying host responses or characteristics associated with protection against HIV infection. Previously, immune quiescence has been associated with HIV resistance. The aim of this study was to compare the level of IA and systemic inflammation in HIV- individuals from South Africa (SA) who were either in relationships with HIV-infected or uninfected stable partners, to evaluate markers of HIV exposure or resistance.
Methods: A heterosexual couples cohort of 103 HIV- individuals with long-term stable HIV- concordant partners (HIV- unexposed) and 113 HIV- individuals with HIV+ discordant partners (HIV- exposed) were included in this study. T cell activation and proliferation (CD38, HLA-DR, CCR5, Ki67) in blood was assessed by flow cytometry. Cytokines in plasma were evaluated by Luminex.
Results: HIV- exposed individuals had lower frequencies of CD4+ T-cells in blood expressing the CCR5 [alone (p=0.05) or in combination with Ki67 (p=0.05) or CD38 (p=0.05)] than HIV-unexposed individuals. Similarly, HIV- exposed individuals had significantly lower frequencies of CD8+ T-cells in blood expressing CCR5 [alone (p=0.05) or in combination with Ki67 (p=0.01) and CD38 (p=0.05)] and HLA-DR (p=0.01) than their HIV- unexposed counterparts. Plasma concentrations of IL-2 (p=0.02), IFN-γ (p=0.05) and GM-CSF (p=0.006, stayed sig. after adjustment for multiple comparisons) were significantly lower in HIV- exposed compared to HIV- unexposed individuals.
Conclusions: This study suggests that HIV- exposed individuals from SA have an immune quiescent phenotype, with lower frequencies of activated CCR5-expressing T-cells and CCR5 density per T cell, than their HIV- unexposed counterparts. Since CCR5 expressing T-cells, especially activated ones, are the preferred targets for HIV infection, this study in HIV- discordant couples suggests that CCR5 agonists may be useful to block HIV infection.
