Before revision:  Here we show that epistasis can be inferred from the pair-wise information between residues, and study how epistasis and information have changed over the long-term. Using HIV-1 protease sequence data from public databases covering the years 1998-2006 (from both treated and untreated subjects), we show that drug treatment has increased the protease's per-site entropies on average.
After revision:  Here we analyze the evolution of epistasis in the protease of the human immunodeficiency virus type 1 (HIV-1) using genomic sequences collected for almost a decade from treated and untreated subjects), we show that drug treatment has increased the protease's per-site entropies on average.