Transmission of S230R integrase drug resistance mutation affecting second-generation integrase inhibitors in a French primary HIV-1 infected man

In France, regular surveillance studies in individuals at the time of HIV-1 primary infection allow monitoring of emergence of transmitted drug-resistance-associated mutations (TDRAMs), HIV genetic diversity shifts and global transmission patterns.1,2 Since 1999, the emergence of TDRAMs has remained stable, at between 10% and 12% of new infections.2 In Europe, Miranda et al.3 reported a TDRAM prevalence of around 10% between 2011 and 2019, with a majority of NRTI and NNRTI mutations. Although there has been an increased use of integrase strand transfer inhibitors (INSTIs), a very low prevalence of TDRAMs has been documented.2,4 Recently, a prevalence of INSTI TDRAMs of 0.30% was described in ART-naive patients from Mediterranean Europe.5 The frequency of resistance-associated mutations (RAMs) may vary in the viral pool, with those that are less fit identified only at a low frequency in the viral quasi-species. Sanger-based sequencing (SBS), the most common method used to detect all HIV-1 resistance mutations, is limited in its sensitivity, enabling the identification of mutations only if present in at least 15%–20% of the viral population. Thus, variants that may be present in a minor proportion of the viral quasi-species are missed.