Open AccessSwitching to bictegravir/emtricitabine/tenofovir alafenamide maintained HIV-1 RNA suppression in participants with archived antiretroviral resistance including M184V/I
Author(s) -
Kristen Andreatta,
Madeleine Willkom,
Ross Martin,
Silvia Chang,
Lilian Wei,
Hui Liu,
Ya-Pei Liu,
Hiba Graham,
Erin Quirk,
Hal Martin,
Kirsten White
Publication year - 2019
Publication title -
the journal of antimicrobial chemotherapy/journal of antimicrobial chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.124
H-Index - 194
eISSN - 1460-2091
pISSN - 0305-7453
DOI - 10.1093/jac/dkz347
Subject(s) - emtricitabine , resistance mutation , dolutegravir , tenofovir alafenamide , virology , abacavir , medicine , genotyping , drug resistance , integrase inhibitor , rilpivirine , cmin , reverse transcriptase , oncology , pharmacology , human immunodeficiency virus (hiv) , genotype , biology , viral load , genetics , antiretroviral therapy , rna , pharmacokinetics , cmax , gene
Objectives Studies 1878 and 1844 demonstrated non-inferior efficacy of switching suppressed HIV-1-infected adults to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) versus continuing boosted PI-based triple regimens or dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). Here, detailed analyses of pre-existing resistance in the two BIC/FTC/TAF switch studies and efficacy at week 48 are described. Methods Pre-existing resistance was assessed from historical genotypes (documented resistance to study drugs was excluded) and by retrospective baseline proviral archive DNA genotyping from whole blood. Outcomes were based on HIV-1 RNA at week 48 with missing values imputed using the last on-treatment observation carried forward method. Results Cumulative pre-existing resistance data from historical and proviral genotypes were obtained for 95% (543/570) of participants who switched to BIC/FTC/TAF. Altogether, 40% (217/543) had one or more pre-existing primary resistance substitutions in protease, reverse transcriptase and/or integrase. Pre-switch NRTI resistance was detected in 16% (89/543) of BIC/FTC/TAF-treated participants, with M184V or M184I detected by proviral genotyping in 10% (54/543). At week 48, 98% (561/570) of all BIC/FTC/TAF-treated participants versus 98% (213/217) with pre-existing resistance and 96% (52/54) with archived M184V/I had HIV-1 RNA <50 copies/mL. No BIC/FTC/TAF-treated participants developed treatment-emergent resistance to study drugs. Conclusions Pre-existing resistance substitutions, notably M184V/I, were unexpectedly common among suppressed participants who switched to BIC/FTC/TAF. High rates of virological suppression were maintained in the overall study population and in those with pre-existing resistance, including M184V/I, for up to 48 weeks of BIC/FTC/TAF treatment with no resistance development. These results indicate that BIC/FTC/TAF is an effective treatment option for suppressed patients, including those with evidence of archived NRTI resistance.