Historical changes in amino acid sequence at position 375 in diverse clades and distinct geographic regions. Env sequences from samples collected worldwide between 1979 and 2015 were examined. Totals of 335, 1,942, 1,248, and 543 Envs were used, from clades A1, B, C, and CRF01_AE, respectively. (A) Changes in frequencies of residues at position 375 in different clades. Values represent percentages of isolates from each 5-to-7-year period that contained the indicated residue. (B) Changes in frequencies of residues at position 375 in the indicated geographic regions. The residues shown in panels A and B account in most cases for more than 95% of all circulating strains. Sequences were analyzed phylogenetically to include a single Env from each patient (see Materials and Methods). For accuracy, only data from time periods with more than 25 patients are included for each clade and region. The following abbreviations are used: for clade B, NA, North America; EU, Europe; AS, Asia; for clade C, SA, Southern Africa (South Africa and Botswana); ECA, Eastern and Central Africa; IN/NP, India and Nepal; for CRF01_AE, CN, China; TH, Thailand.