Secondary Integrase Resistance Mutations Found in HIV-1 Minority Quasispecies in Integrase Therapy-Naive Patients Have Little or No Effect on Susceptibility to Integrase Inhibitors

摘要: The goal of this study was to explore the presence integrase strand transfer inhibitor (InSTI) resistance mutations in HIV-1 quasispecies present InSTI-naive patients and evaluate their vitro effects on phenotypic susceptibility InSTIs replication capacities. RT-RNase H-IN region PCR amplified from plasma viral RNA obtained 49 subtype B-infected (21 drug naive 28 failing highly active antiretroviral therapy [HAART] not containing InSTIs) recombined with an HXB2-based backbone RT IN deleted. Recombinant viruses were tested against raltegravir elvitegravir for capacity. Three-hundred forty-four recombinant successfully analyzed both phenotypically genotypically. majority clones resistant InSTIs: 0/344 showed resistance, only 3 (0.87%) low-level resistance. No primary found as major or minor species. secondary also absent rarely present. Secondary mutations, such T97A G140S, minority quasispecies, elvitegravir-resistant clones. A novel mutation, E92G, although Preexisting genotypic extremely rare confined a restricted variants. Overall, these results, together others based population ultradeep sequencing, suggest that at point genotyping all before treatment may be cost-effective should recommended until evidence transmitted clinical relevance variants/polymorphisms is determined.