Abstract
Antiretroviral therapy containing an integrase strand transfer inhibitor (INSTI) plus two NRTIs has become the recommended treatment for antiretroviral-naive HIV-1-infected patients in the updated guidelines. We aimed to determine the prevalence of INSTI-related mutations in Taiwan. Genotypic resistance assays were performed on plasma from ARV-naïve patients (N = 948), ARV-experienced but INSTI-naive patients (N = 359), and raltegravir-experienced patients (N = 63) from 2006 to 2015. Major INSTI mutations were defined according to the IAS-USA list and other substitutions with a Stanford HIVdb score ≧ 10 to at least one INSTI were defined as minor mutations. Of 1307 HIV-1 samples from patients never exposed to INSTIs, the overall prevalence of major resistance mutations to INSTIs was 0.9% (n = 12), with an increase to 1.2% in 2013. Of these 12 sequences, 11 harboured Q148H/K/R, one Y143R, and none N155H. Of 30 sequences (47.6%) with INSTI-resistant mutations from raltegravir-experienced patients, 17 harboured Q148H/K/R, 8 N155H, and 6 Y143C/R. Other than these major mutations, the prevalence of minor mutations were 5.3% and 38.1%, respectively, in ARV-naive and raltegravir-experienced patients. The overall prevalence of INSTI mutations remains low in Taiwan. Surveillance of INSTI resistance is warranted due to circulation of polymorphisms contributing to INSTI resistance and expected increasing use of INSTIs.
Highlights
Integrase strand transfer inhibitor (INSTI)-based regimens are recommended as first-line combination antiretroviral therapy in several updated treatment guidelines for HIV after the efficacy of the three integrase strand transfer inhibitor (INSTI) has been demonstrated in randomized clinical trials[1,2,3,4,5,6,7,8]
From June 2006 to October 2015, a total of 1370 non-duplicated blood specimens were subjected to genotypic analysis of INSTI resistance at the National Taiwan University Hospital (NTUH)
When the current regimens used by the ART-experienced patients were analyzed, we found that zidovudine/lamivudine, abacavir/lamivudine, and tenofovir disoproxil fumarate (TDF)/emtricitabine or TDF and lamivudine were the major nucleos(t)ide reverse-transcriptase inhibitor (NRTIs) backbone antiretrovirals that were used in these patients (Table 2)
Summary
Integrase strand transfer inhibitor (INSTI)-based regimens are recommended as first-line combination antiretroviral therapy (cART) in several updated treatment guidelines for HIV after the efficacy of the three INSTIs (raltegravir, elvitegravir, and dolutegravir) has been demonstrated in randomized clinical trials[1,2,3,4,5,6,7,8]. With the widespread use of INSTIs, surveillance of the prevalence of INSTI resistance among ART-naive patients is critical in optimizing ART efficacy, given the concerns that INSTI, raltegravir and elvitegravir, have a relatively lower genetic barrier to emergence of resistance mutations when compared with boosted PIs9. Polymorphisms in integrase, which might modulate the efficacy of raltegravir and elvitegravir, have been reported and observed in patients receiving INSTI-containing regimens with virological failure. An increased frequency in HIV-1 integrase polymorphisms in patients with treatment failure and/or patients with reverse-transcriptase resistance mutations was reported[13]. We aimed to determine the prevalence of INSTI-resistant mutations in ART-naive patients, and to compare the prevalence of INSTI-resistant mutations/polymorphisms between ART-naive, ART-experienced/
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