Before revision:  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. At the same time, the sum of mutual entropies across all pairs of residues within the protease shows a significant increase over the years, indicating an increase in epistasis in response to treatment, a trend not seen within sequences from untreated subjects.
After revision:  Using HIV-1 protease sequence data from public databases covering the years 1998-2006 (from both treated and untreated patients, to understand how proteins adapt to a changing environment of treatment over time. We show that mutual information between pairs of residues within the protease shows a significant increase over the years, indicating an increase in epistasis in response to treatment, a trend not seen within sequences from untreated subjects.