Identification of biased amino acid substitution patterns in human immunodeficiency virus type 1 isolates from patients treated with protease inhibitors

Human immunodeficiency virus type 1 (HIV-1) amino acid substitutions observ ed during antiretroviral drug therapy may be caused by drug selection, non- drug-related evolution, or sampling error introduced by the sequencing proc ess. We analyzed HIV-1 sequences from 371 untreated patients and from 178 p atients receiving a single protease inhibitor. Amino acid substitution patt erns during treatment were compared with inferred substitution patterns ari sing evolutionarily without treatment. Our results suggest that most treatm ent-associated amino acid substitutions are caused by selective drug pressu re, including substitutions not previously associated with drug resistance.