First characterization of insertions in the HIV-1 integrase-coding region from people with HIV.

OBJECTIVES

This study aimed to gain a better understanding of the role of insertional mutations in the integrase (IN)-coding sequence of 13 HIV-1-infected people.

RESULTS

Here, we present the first documentation of amino acid insertion in the IN-coding sequence of HIV-1-infected people at positions 168, 253, 255 and 260. The consequences of these mutations in terms of viral replication and resistance to INSTIs were analysed using virological and biochemical assays and 3D modelling. Analysis of viral genomes by quantitative PCR demonstrated that insertional mutations reduce reverse transcription efficiency and had different impacts on viral integration. Taken together, we showed that mutants were delayed in their replication. Virological assays using two potent strand-transfer inhibitors (INSTIs), raltegravir and dolutegravir, demonstrated that no resistance to INSTIs was observed.

CONCLUSIONS

Our study has revealed that the mutations observed in people living with HIV-1 do not confer resistance to anti-integrase compounds but are detrimental to viral replication.