Publication date: 

2017-01-01 00:00:00

Ref: 

. J Antimicrobial Chemother 2017; 72: 227-234

Author(s): 

Cunningham E, Chan YT, Aghaizu A, Bibby DF, Murphy G, Tosswill J, Harris RJ, Myers R, Field N, Delpech V, Cane PA, Gill ON, Mbisa JL.

Publication type: 

Article

Abstract: 

Objectives To determine the prevalence of inferred low-frequency HIV-1 transmitted drug resistance (TDR) in MSM in the UK and its predicted effect on first-line therapy. Methods The HIV-1 pol gene was amplified from 442 newly diagnosed MSM identified as likely recently infected by serological avidity testing in 2011–13. The PCR products were sequenced by next-generation sequencing with a mutation frequency threshold of >2% and TDR mutations defined according to the 2009 WHO surveillance drug resistance mutations list. Results The majority (75.6%) were infected with subtype B and 6.6% with rare complex or unique recombinant forms. At a mutation frequency threshold of >20%, 7.2% (95% CI 5.0%–10.1%) of the sequences had TDR and this doubled to 15.8% (95% CI 12.6%–19.6%) at >2% mutation frequency (P < 0.0001). The majority (26/42, 62%) of low-frequency variants were against PIs. The most common mutations detected at >20% and 2%–20% mutation frequency differed for each drug class, these respectively being: L90M (n = 7) and M46IL (n = 10) for PIs; T215rev (n = 9) and D67GN (n = 4) for NRTIs; and K103N (n = 5) and G190E (n = 2) for NNRTIs. Combined TDR was more frequent in subtype B than non-B (OR = 0.38; 95% CI = 0.17–0.88; P = 0.024) and had minimal predicted effect on recommended first-line therapies. Conclusions The data suggest differences in the types of low-frequency compared with majority TDR variants that require a better understanding of the origins and clinical significance of low-frequency variants. This will better inform diagnostic and treatment strategies.