Background:
Clinical trials and real-life experience have shown limited resistance development after use of second generation INSTIs, specially in first line. One of the mutants found in this scenario is the R263K, a nonpolymorphic mutation that alone reduces DTG, BIC, and CAB susceptibility about 2-fold. This mutation has been described in first line failure to second generation INSTIs.
Methods:
We analyzed all the samples submitted for integrase resistance genotype (Abbot ViroSeq HIV 1 Genotyping System) to our reference laboratory from October 2021 to September 2023. Our lab that performs all the resistance tests from 25 states in México, centers that care for about 2/3 of the cases in the country. In all cases the test was ordered to detect integrase resistance.
Results:
Ninety-four samples were submitted to integrase resistant tests to our referral laboratory; 77(72%) have RAMs to INSTIs, but only 19 (18%) had primary resistant mutants in 12 of them accompanied by secondary mutations. The most common mutants detected were the combination of Q148H plus G140S in eight cases, all failing to DTG BID after previous failure to RAL; followed by mutation R263K present in 7 cases 6 of them detected in 2023 tests. R263K was detected in 2cases failing to DTG and 3 to Bictegravir/TAF/emtricitabine (BIC/TAF/FTC) used as a first line treatment. All cases failing to BIC/TAF/FTC had R263K together with M50I, and were failing for at least one year, always with viremias lower than 5,000 copies/ml.
Conclusions:
Despite the widespread use in México of second generation INSTIs, especially after 2019 were BICTAF is used as first line treatment in close to 90% of starting cases; the number of failures is limited. Only 18% of the tests submitted had primary mutations in the integrase gene, mostly in failures after RAL use. The 3 cases of resistance to BIC/TAF/FTC in first line showed a rare mutant combination associated to low viral fitness, and are probably related to bad adherence.