Evolution and emergence of the integrase inhibitor 231 insertion resistance mutation in an HIV-2 strain isolated in central Portugal.

Limited in vivo data are available regarding the recently described integrase (IN) codon 231 insertion mutation in Human immunodeficiency virus 2 (HIV-2) because this new resistance pathway to integrase strand transfer inhibitors (INSTIs) has only been found in very few clinical isolates. This study reports the emergence of the IN codon 231 insertion resistance mutation in an HIV-2 strain isolated from a person with HIV-2 (PWH-2) undergoing antiretroviral treatment with a raltegravir (RAL) containing regimen, in central Portugal. Longitudinal nucleotide sequences of the IN coding region (codons 1-293) obtained prior to and at the time of treatment failure were retrospectively analyzed for genotypic resistance to antiretroviral drugs. The 5 amino acid insertion mutation between codons 231 and 232 was detected in the IN C-terminal domain of an HIV-2 group A strain 156 months after initiation of a RAL-containing regimen. The insertion mutation was not present before exposure to RAL. No other resistance-associated mutation to INSTIs was detected at the time of treatment failure. The insertion profile found, GYRGK, was similar to those previously described, and clearly emerged under the selective pressure of RAL, which is in agreement with previously reported evidence of a significant correlation between treatment failure to INSTIs and the emergence of R231_insert containing viruses. Our findings expand the available genotypic data regarding this resistance pathway and should help to improve HIV-2 resistance interpretation algorithms.