Therapeutics against the envelope (Env) proteins of human immunodeficiency virus type 1 (HIV-1) effectively reduce viral loads in patients. However, due to mutations, new therapy-resistant Env variants frequently emerge. The sites of mutations on Env that appear in each patient are considered random and unpredictable. We developed an algorithm to estimate for each patient the mutational state of each position based on the mutational state of adjacent positions on the three-dimensional structure of the protein. We developed a dynamic ensemble selection algorithm designated ‘k-best classifiers’ (KBC). It identifies the best classifiers within the neighborhood of a new observation and applies them to predict the variability state of each observation. To evaluate the algorithm, we applied amino acid sequences of Envs from 300 HIV-1-infected individuals (at least six sequences per patient).