Transmitted Drug Resistance (TDR) can impair first-line antiretroviral therapy response. Moreover, HIV-1 minority resistant variants (MRV) can be a source of virological failure if they are present before antiretroviral treatment: it was mainly shown for non nucleoside reverse transcriptase inhibitors first line based regimens. Few data are available for TDR Integrase Strand Transfer Inhibitors (ISTIs). In this work, we have studied resistance mutations in integrase gene by Sanger sequencing and UltraDeep Sequencing (UDS) in ISTI-naive patients.
Integrase genotypic analysis was performed by Sanger sequencing and by UDS. Plasma samples of 65 treatment-naïve Men having Sex with Men (MSM) patients were analyzed from the amino acid 53 to 281. GS Amplicon Variant Analyzer was used to analyze the UDS data, with a detection threshold of MRV of 1% (forward and reverse). Resistance was interpreted according to the last version of ANRS algorithm (www.hivfrenchresistance.org).
Among the 65 patients, 60% of them were infected by B subtype. Viruses of six patients harbored majority resistant mutations by Sanger sequencing (four L74I and two E157Q mutations). Three viruses harbored MRV detected by UDS only: two R263K (at a rate of 9.7%, mutational load: 7099 copies/mL; and 13.5 %, 8345 copies/mL) and one E138K mutations (at 4.8%, 111 copies/mL). All these mutations were retrieved among B subtype viruses.
None of the three classical ISTIs signature resistance mutations (at positions 143, 148 and 155) were retrieved. However, in this population of MSM naive-treatment patients, the prevalence of ISTI-resistance mutations, mainly related to polymorphisms, seems to be relatively high (9.2% by Sanger and 13.8% by UDS). In conclusion, with the increase use of ISTIs in clinical practice, TDR for this therapeutic class should be carefully monitored in the future, as well as the impact of these MRV on the virological response.