Fig. 3

Amino acid variants with significant trends in frequency over time. The median frequencies of variants corresponding to the consensus B reference sequence within each period are indicated by filled circles with blue error bars indicating the 5th–95th percentile ranges. The median frequencies of variants differing from the consensus B reference sequence within each period are indicated by filled squares with red error bars indicating the 5th–95th percentile ranges. The median predicted slopes are depicted in blue or red solid lines. The 5th–95th percentile ranges of the model-predicted trends are indicated by dotted lines. Predicted slopes sl are given in units %/year. Positions are grouped by the three functional domains of the integrase. Positions showing trends in INSTI resistance-associated variants are shaded grey. *** time trend is significant at the P < 0.01 level, ** time trend is significant at the P < 0.05 level