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The purpose of this study is to survey and synthesize recent progress in soluble biomarkers relevant to HIV-1 disease stages, progression and comorbidities.Soluble biomarkers in plasma and other body fluids provide insight into many aspects of HIV-1 disease. Chemokines and defensins in breast milk and cervicovaginal secretions have been associated with HIV-1 susceptibility and transmission. Acute infection plasma cytokine storm components, including serum amyloid A, IFNγ-induced protein 10, interleukin (IL)-12, interferon-gamma (IFNγ), IL-7 and IL-15, may help predict viral load set-point and the subsequent disease progression. During chronic infection, IL-6, soluble (s)CD14, sCD163, high-sensitivity C-reactive protein, D-dimer, fibrin and hyaluronic acid can help predict comorbidities, and to some extent disease progression and mortality, in patients both on and off antiretroviral therapy. Furthermore, recent results suggest that assessment of combinations of soluble biomarkers may prove more powerful than the single factors alone in predicting disease.Soluble biomarkers help us understand HIV-1 immunopathogenesis. Integration of many biomarkers derived from a single plasma sample might become a powerful tool to optimize and individualize treatment and care.