Soluble biomarkers in acute HIV infection reveal insight into HIV reservoir

Background: Several biomarkers are induced during acute HIV infection, remain elevated during ART, and have been associated with disease progression. However, their role in HIV pathogenesis and reservoir establishment remains unclear. We explored HIV-associated biomarker signatures longitudinally and their relationship with HIV reservoir dynamics following ART initiation. Methods: 82 biomarkers were assessed by Luminex bead technology in Thai individuals at baseline, prior to HIV infection, and during viral upslope (d1-d5), peak viral load (d9-d15), early chronic (∼7m-8m) and late chronic (∼2y) timepoints following infection in ART-naive (n=13) or individuals who began continuous ART during acute HIV infection (n=40) from the ongoing RV217 and RV254 trials. HIV-1 viral loads (VL) were assessed by HIV RNA in peripheral blood and cell-associated DNA. Results: Distinct biomarker pathways were induced with differential temporal kinetics in HIV acute infection. Proinflammatory markers (e.g. MCP-1, MCP-2) significantly rose during acute infection but resolved by chronic timepoints. TNF-α- and IFN-γ-signaled pathways were induced during peak viremia and persisted in ART-naïve individuals. During acute infection, levels of MIP-3β, sTNFR-II, IP-10, I-TAC, TNF-α, MIG, sTNFR-II, MCP-1, and MCP-2 correlated positively HIV VL (p<0.01, all). In individuals given ART during acute infection, rate of HIV RNA decline in plasma was correlated with levels of MIP-3β (r = -0.318; p=0.04), I-TAC (r=-0.354; p=0.03), and IP-10 (r=-0.322; p=0.04) prior to ART initiation. Levels of cell-associated HIV DNA at week 96 post treatment initiation correlated with levels of sTNFR-II (r=0.407; p=0.04) prior to ART. HIV-associated biomarkers TNF-α, sTNFR-I, sTNFR-II, IP-10, MIG, and I-TAC remained elevated at chronic infection during treatment relative to HIV-uninfected individuals (p<0.05, all), indicating biomarkers associated with HIV VL remain elevated in the absence of detectable virus in circulation. Conclusion: A comprehensive analysis of biomarkers induced in HIV infection reveal viral-associated factors that remain elevated despite successful ART. Levels of these markers correlate with rate of viral decline after treatment and with levels of viral reservoir two years following infection. The use of these markers to better inform treatment interruption and immune therapies remains under study. (Figure Presented).