The present invention relates to a method for in vitro detection and/or monitoring of a disease in a sample, based on measurement of enzymatic activity of proteases activated and secreted upon disease development, to modified peptides used for the enzymatic detection of the proteases, the use of the peptides, a kit comprising such peptides and the use of ADAM-protease activity as a surrogate marker for disease burden and activity in infectious, inflammatory, and malignant diseases, such as HIV infection and melanoma.