**1. Introduction**

Ritonavir-boosted atazanavir has become increasingly important as an option for second-line therapy in low- and middle-income countries (LMICs) [1]. Although it appears to have comparable efficacy to ritonavir-boosted lopinavir (lopinavir/r) [2,3], there are few data on the mutations arising in patients receiving boosted or unboosted atazanavir

**Citation:** Rhee, S.-Y.; Boehm, M.; Tarasova, O.; Di Teodoro, G.; Abecasis, A.B.; Sönnerborg, A.; Bailey, A.J.; Kireev, D.; Zazzi, M.; the EuResist Network Study Group; et al. Spectrum of Atazanavir-Selected Protease Inhibitor-Resistance Mutations. *Pathogens* **2022**, *11*, 546. https://doi.org/10.3390/ pathogens11050546

Academic Editor: Richard Y. Zhao

Received: 23 March 2022 Accepted: 3 May 2022 Published: 5 May 2022

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compared with the extensive data available for lopinavir/r [4–12]. Characterizing the spectrum of mutations arising in patients receiving atazanavir, whether boosted or unboosted, provides an insight into the genetic barrier to atazanavir resistance and into the use of boosted darunavir (darunavir/r) for third line therapy in LMICs.

Therefore, in this paper, we analyze publicly available protease sequences from previously protease inhibitor (PI)-naïve patients with virological failure (VF) on a boosted or unboosted atazanavir-containing regimen. We compare the spectrum of protease mutations observed in patients with subtype B as opposed to non-B viruses, in patients receiving boosted as opposed to unboosted atazanavir, and in patients with early PI resistance (e.g., harboring few PI-associated drug-resistance mutations (DRMs)) with advanced PI resistance (e.g., harboring four or more PI-associated DRMs). We also examine the predicted susceptibility of the different patterns of atazanavir-selected mutations to lopinavir/r and darunavir/r.
