Distinct biomarker signatures in HIV acute infection associate with viral dynamics and reservoir size

Estimating the size of the viral reservoir is critical for HIV cure strategies. Biomarkers in peripheral circulation may give insights into the establishment of the viral reservoir in compartments not easily accessible. We therefore measured systemic levels of 84 soluble biomarkers belonging to a broad array of immune pathways in acute HIV infection in both antiretroviral therapy-naive (ART-naive) individuals as well as individuals who began ART upon early detection of HIV infection. These biomarkers were measured longitudinally during acute and chronic infection and their relationship to viral reservoir establishment and persistence was assessed. We observed several distinct biomarker pathways induced following HIV infection such as IFN-γ-signaled chemokines, proinflammatory markers, and TNF-α-family members. Levels of several of these factors directly correlated with contemporaneous viral loads and/or frequency of peripheral blood mononuclear cells harboring HIV DNA during acute HIV infection. MCP-1, MIP-3β, sTNFR-II, and IL-10 levels prior to ART associated with HIV DNA levels after 96 weeks of treatment, suggesting a link between early immune signaling events and the establishment and persistence of the viral reservoir during ART. Furthermore, they offer potentially novel tools for gaining insight into relative reservoir size in acutely infected individuals and the potential of associated risks of treatment interruption.