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. 2021 Sep 2;10:e69032. doi: 10.7554/eLife.69032

Figure 2. Cohort analyses of individuals with HIV reveal drug resistance evolution is ongoing after years on therapy, stepwise and partially predictable.

Figure 2.

(A) The yearly probability of resistance evolution conditional on no prior resistance evolution in a large cohort of individuals in British Columbia treated with triple drug therapies (Rocheleau et al., 2018). Conditional evolution probabilities are plotted separately for resistance to 3TC or FTC (dark blue), NNRTIs (red), NRTIs other than 3TC or FTC (light blue) or PIs (yellow). Drug-category specific fits to an exponential model covering years 2–10 and r2 describing the model fit are also plotted. Bars represent 95% confidence intervals. (B) Across individuals treated with three-drug combination therapies based on two NRTIs paired with an NNRTI (top) or PI (bottom), many sequences are detected with 0, 1, 2, or 3+ drug resistance mutations in a large cohort (data source: Feder et al., 2016a). (C) In individuals treated with three-drug combination therapies based on two NRTIs paired with an NNRTI (top) who have exactly one resistance mutation, that mutation most often confers resistance to the NNRTI of the treatment (red), although sometimes resistance to 3TC (dark blue) or the other NRTI (light blue) develops. Among individuals treated with a PI paired with 3TC and a second NRTI who have a single drug resistance mutation, that mutation most often confers resistance to 3TC (dark blue), although sometimes it confers resistance to the other NRTI (light blue) or the PI (yellow). Asterisks mark treatments for which the first mutation confers resistance to the NNRTI (top) or 3TC (bottom) more often than expected under the relative mutation probabilities of the three drugs (binomial test, 5% false discovery rate). (Data source: Feder et al., 2016a). Each square in both B and C represents a single individual, and the sample sizes are given next to the treatment names. Abbreviations: abacavir, ABC; indinavir, IDV; lamivudine, 3TC; lopinavir, LPV; nelfinanvir, NFV; stavudine, D4T; saquinavir, SQV; zidovudine, AZT.