HIV elite controllers have lower frequencies of CD14dimCD16+ inflammatory monocytes with greater CX3CR1-dependent tissue homing potential than viremic controllers (VIR9P.1138)

Abstract Without antiretroviral therapy, a small fraction of HIV-infected patients does not progress to AIDS. Such elite controllers (EC) or viremic controllers (VC) maintain undetectable or low levels of viremia, respectively. Generation of broadly neutralizing antibodies (bNAb) does not correlate with viral control, but might enhance antibody-dependent cellular phagocytosis by monocytes. Monocytes are classified into CD14+CD16-, CD14+CD16+ and CD14dimCD16+ monocytes. The latter show increased inflammatory responsiveness and are elevated during chronic HIV-1 infection. We measured markers of T cell activation and monocyte subset distribution and quantity, and investigated the relationship between these parameters and production of bNAb to identify markers for the development of bNAbs. We showed that VC display increased frequencies of CD38+ CD4+ and CD8+ T cells compared to EC. Our data also show that elevated frequencies of CD8+CD38+HLA-DR+ T cells and CD14dimCD16+ monocytes were associated with both viremic control status and production of bNAbs. bNAb production was also strongly associated with increased frequency of CD57+HLA-DR+ CD8+ T cells, as well as decreased expression of chemokine receptors CCR2 and CX3CR1 on CD14dimCD16+ monocytes in VC compared to EC. Further studies are required to establish the cause and effect of alterations in monocyte populations during HIV-1 infection and whether these could tip the scale towards viral control below detectable levels.