High-throughput sequencing reveals a high prevalence of pretreatment HIV-1 drug resistance in Sweden.

Objectives: HIV-1 pretreatment drug resistance (PDR) is a global concern. Our aim was to evaluate high-throughput sequencing (HTS) for HIV-1 resistance testing and describe PDR in Sweden, where 75% of diagnosed individuals are foreign-born.

Design: Cross-sectional study.

Methods: Individuals entering HIV-1 care in Sweden 2017 to March 2019 (n = 400) were included if a viremic sample was available (n = 220). HTS was performed using an in-house assay. Drug resistance mutations (DRMs) (based on Stanford HIV DB vs. 8.7) at levels 1-5%, 5-19% and at least 20% of the viral population were described. Results from HTS and routine Sanger sequencing were compared.

Results: HTS was successful in 88% of patients, 92% when viral load was at least 1000 copies/ml. DRMs at any level in protease and/or reverse transcriptase were detected in 95 individuals (49%), whereas DRMs at least 20% in 35 (18%) individuals. DRMs at least 20% correlated well to findings in routine Sanger sequencing. Protease/reverse transcriptase (PR/RT) DRMs at least 20% were predicted by treatment exposure; adjusted OR 9.28 (95% CI 2.24-38.43; P = 0.002) and origin in Asia; adjusted OR 20.65 (95% CI 1.66-256.24; P = 0.02). Nonnucleoside reverse transcriptase inhibitor (NNRTI) DRMs at least 20% were common (16%) and over-represented in individuals originating from sub-Saharan Africa or Asia. Low-level integrase strand transfer inhibitor (INSTI) DRMs less than 20% were detected in 15 individuals (8%) with no association with INSTI exposure.

Conclusion: Our HTS can efficiently detect PDR and findings of DRMs at least 20% compare well to routine Sanger sequencing. The high prevalence of PDR was because of NNRTI DRMs and associated with migration from areas with emerging PDR.