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  1. Article ; Online: Sequence characterization of extracellular HBV RNA in patient plasma.

    Chang, Silvia / Hedskog, Charlotte / Parhy, Bandita / Martin, Ross / Mo, Hongmei / Maiorova, Evguenia / Zoulim, Fabien

    Journal of viral hepatitis

    2022  Volume 30, Issue 1, Page(s) 29–38

    Abstract: Antiviral nucleos(t)ide analogue therapies inhibit HBV replication and suppress the HBV DNA levels in patients with chronic HBV infection. Since HBV RNAs are expressed from cccDNA or HBV integrated sequences, independently of viral genome replication, ... ...

    Abstract Antiviral nucleos(t)ide analogue therapies inhibit HBV replication and suppress the HBV DNA levels in patients with chronic HBV infection. Since HBV RNAs are expressed from cccDNA or HBV integrated sequences, independently of viral genome replication, levels of HBV RNAs in plasma may remain high following treatment with nucleos(t)ide analogue. Thus, HBV RNAs have been proposed to be used as a viral biomarker for treatment outcome and disease progression. Recent investigations of plasma HBV RNAs described the presence of full length as well as subgenomic forms of RNA. To support the usage of plasma HBV RNAs as a viral biomarker, further understanding of HBV RNA composition in clinical samples is needed. Here, sequence of extracellular HBV RNAs was characterized in plasma samples of patients with chronic HBV infection using two independent RNA amplification methods that do not use HBV-specific primers for amplification: total RNA (NuGEN RNAseq) and mRNA (TruSeq RNAseq). Sequencing coverage was obtained across the full length of HBV genome for both methods, confirming the presence of full-length HBV RNA in plasma. The sequence of HBV RNA was nearly identical to plasma HBV DNA sequence in each sample with only 0-14 (median 4) mismatches over 3 kb. Thus, sequence of HBV RNA plasma reflects the intrahepatic viral reservoir and can be used for monitoring of sequence variants such as resistance in clinical trials. Additionally, RNA splice forms, different polyA tails start positions and presence of HBV-human chimeric transcript were identified.
    MeSH term(s) Humans ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Biomarkers ; DNA, Viral ; Hepatitis B virus/genetics ; RNA, Viral ; Virus Replication ; Subgenomic RNA
    Chemical Substances Antiviral Agents ; Biomarkers ; DNA, Viral ; RNA, Viral ; Subgenomic RNA
    Language English
    Publishing date 2022-10-17
    Publishing country England
    Document type Journal Article
    ZDB-ID 1212497-7
    ISSN 1365-2893 ; 1352-0504
    ISSN (online) 1365-2893
    ISSN 1352-0504
    DOI 10.1111/jvh.13760
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Generation of an HBV core phenotyping assay for evaluating HBV capsid compounds

    Liu, Yang / Chang, Silvia / Hsieh, David / Burdette, Dara / Martin, Ross / Mo, Hongmei / Feierbach, Becket

    Journal of virological methods. 2021 June, v. 292

    2021  

    Abstract: Hepatitis B virus (HBV) capsids are assembled from HBV core protein and assembly is a critical step in the propagation of the virus. Due to its multiple functions in the viral life cycle, core is an attractive target for new antiviral therapies. For HBV ... ...

    Abstract Hepatitis B virus (HBV) capsids are assembled from HBV core protein and assembly is a critical step in the propagation of the virus. Due to its multiple functions in the viral life cycle, core is an attractive target for new antiviral therapies. For HBV capsid assembly modulators (CAMs), several resistance mutants have been identified, both from the clinic and in vitro. However, currently there is no convenient in vitro assay to monitor resistance to CAMs in the clinic. Here, we developed a facile, cassette-based phenotyping assay to assess the antiviral activity of CAMs on a panel of clinical isolates. Using this system, the core genes from 13 patients infected with HBV genotypes A–H were expressed as chimeric virus and tested for sensitivity to CAMs. No substantial differences in antiviral activity were observed across genotypes due to the conservation of the drug binding pocket. In addition, we tested a panel of constructs encoding 13 single amino acid polymorphs in the CAM binding site, including some polymorphs with previously-described resistance to CAMs. Overall, 11 of 13 constructs replicated in vitro, 6 constructs showed reduced susceptibility to CAMs. The 11 polymorphs which could replicate in vitro remained sensitive to the nucleotide analog tenofovir alafenamide (TAF), indicating that there is no cross-resistance.
    Keywords Hepatitis B virus ; amino acids ; antiviral properties ; capsid ; cross resistance ; drugs ; phenotype ; viruses
    Language English
    Dates of publication 2021-06
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 8013-5
    ISSN 1879-0984 ; 0166-0934
    ISSN (online) 1879-0984
    ISSN 0166-0934
    DOI 10.1016/j.jviromet.2021.114117
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  3. Article ; Online: Generation of an HBV core phenotyping assay for evaluating HBV capsid compounds.

    Liu, Yang / Chang, Silvia / Hsieh, David / Burdette, Dara / Martin, Ross / Mo, Hongmei / Feierbach, Becket

    Journal of virological methods

    2021  Volume 292, Page(s) 114117

    Abstract: Hepatitis B virus (HBV) capsids are assembled from HBV core protein and assembly is a critical step in the propagation of the virus. Due to its multiple functions in the viral life cycle, core is an attractive target for new antiviral therapies. For HBV ... ...

    Abstract Hepatitis B virus (HBV) capsids are assembled from HBV core protein and assembly is a critical step in the propagation of the virus. Due to its multiple functions in the viral life cycle, core is an attractive target for new antiviral therapies. For HBV capsid assembly modulators (CAMs), several resistance mutants have been identified, both from the clinic and in vitro. However, currently there is no convenient in vitro assay to monitor resistance to CAMs in the clinic. Here, we developed a facile, cassette-based phenotyping assay to assess the antiviral activity of CAMs on a panel of clinical isolates. Using this system, the core genes from 13 patients infected with HBV genotypes A-H were expressed as chimeric virus and tested for sensitivity to CAMs. No substantial differences in antiviral activity were observed across genotypes due to the conservation of the drug binding pocket. In addition, we tested a panel of constructs encoding 13 single amino acid polymorphs in the CAM binding site, including some polymorphs with previously-described resistance to CAMs. Overall, 11 of 13 constructs replicated in vitro, 6 constructs showed reduced susceptibility to CAMs. The 11 polymorphs which could replicate in vitro remained sensitive to the nucleotide analog tenofovir alafenamide (TAF), indicating that there is no cross-resistance.
    MeSH term(s) Antiviral Agents/pharmacology ; Capsid ; Capsid Proteins/genetics ; Hepatitis B virus/genetics ; Humans ; Virus Assembly ; Virus Replication
    Chemical Substances Antiviral Agents ; Capsid Proteins
    Language English
    Publishing date 2021-02-28
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 8013-5
    ISSN 1879-0984 ; 0166-0934
    ISSN (online) 1879-0984
    ISSN 0166-0934
    DOI 10.1016/j.jviromet.2021.114117
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Establishment and Characterization of an HBV Viral Spread and Infectious System following Long-Term Passage of an HBV Clinical Isolate in the Primary Human Hepatocyte and Fibroblast Coculture System.

    Liu, Yang / Kornyeyev, Dmytro / May, Lindsey / Han, Dong / Aeschbacher, Thomas / Chang, Silvia / Martin, Ross / Mo, Hongmei / Feierbach, Becket

    Journal of virology

    2022  Volume 96, Issue 18, Page(s) e0084922

    Abstract: The existing cell culture-based methods to study hepatitis B virus (HBV) have limitations and do not allow for viral long-term passage. The aim of this study was to develop a ... ...

    Abstract The existing cell culture-based methods to study hepatitis B virus (HBV) have limitations and do not allow for viral long-term passage. The aim of this study was to develop a robust
    MeSH term(s) Coculture Techniques ; DNA, Viral/genetics ; Fibroblasts/virology ; Genotype ; Hepatitis B/virology ; Hepatitis B virus/genetics ; Hepatocytes/virology ; Humans ; Mutagenesis ; Mutation ; Virology/methods ; Virus Replication
    Chemical Substances DNA, Viral
    Language English
    Publishing date 2022-08-29
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.00849-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Phenotypic resistance to lenacapavir and monotherapy efficacy in a proof-of-concept clinical study.

    Margot, Nicolas / Vanderveen, Laurie / Naik, Vidula / Ram, Renee / Parvangada, P C / Martin, Ross / Rhee, Martin / Callebaut, Christian

    The Journal of antimicrobial chemotherapy

    2022  Volume 77, Issue 4, Page(s) 989–995

    Abstract: Background: Lenacapavir in vitro resistance selections identified seven mutations in HIV-1 capsid protein (CA) associated with reduced susceptibility.: Objectives: To analyse lenacapavir activity against lenacapavir-associated resistance mutations in ...

    Abstract Background: Lenacapavir in vitro resistance selections identified seven mutations in HIV-1 capsid protein (CA) associated with reduced susceptibility.
    Objectives: To analyse lenacapavir activity against lenacapavir-associated resistance mutations in multiple assays. We also report Day 10 resistance analyses conducted in a Phase 1b study of lenacapavir (Study 4072) in people with HIV (PWH).
    Methods: Mutations were inserted in a proviral DNA clone by site-directed mutagenesis, and viruses (n = 12) were generated by transfection. Sequences were used to generate single-cycle (SC) test vectors that were evaluated in a Gag-Pro assay, and replicative viruses were tested in a multicycle (MC) MT-2 assay to determine lenacapavir susceptibility. Study 4072 was a Phase 1b, double-blinded, placebo-controlled, dose-ranging, randomized study of lenacapavir in untreated PWH. Participants received a single dose of lenacapavir (up to 750 mg) or placebo (10 day monotherapy). CA resistance was characterized using genotypic and/or phenotypic assays.
    Results: Lenacapavir susceptibility in the SC assay showed an inverse relationship between replication capacity and resistance. In Study 4072, all 29 participants receiving lenacapavir showed a robust virological response with no rebound. At baseline, no participant had resistance mutations to lenacapavir, and all had WT susceptibility to lenacapavir. Post-monotherapy analyses revealed the emergence of CA mutation Q67H at Day 10 in two participants.
    Conclusions: In vitro assays confirmed that increased resistance to lenacapavir was associated with decreased replication capacity of mutant viruses. In the clinical study no pre-existing lenacapavir resistance was detected. Emergence of Q67H occurred at exposures below the dose used in current Phase 2/3 studies. These results support development of lenacapavir as an antiretroviral agent.
    MeSH term(s) Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use ; Anti-Retroviral Agents/therapeutic use ; Drug Resistance, Viral/genetics ; HIV Infections/drug therapy ; HIV-1/genetics ; Humans ; Mutation
    Chemical Substances Anti-HIV Agents ; Anti-Retroviral Agents
    Language English
    Publishing date 2022-01-12
    Publishing country England
    Document type Clinical Trial, Phase I ; Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 191709-2
    ISSN 1460-2091 ; 0305-7453
    ISSN (online) 1460-2091
    ISSN 0305-7453
    DOI 10.1093/jac/dkab503
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  6. Article ; Online: Characterization of Hepatitis B virus polymerase mutations A194T and CYEI and tenofovir disoproxil fumarate or tenofovir alafenamide resistance.

    Liu, Yang / Chang, Silvia / Martin, Ross / Flaherty, John / Mo, Hongmei / Feierbach, Becket

    Journal of viral hepatitis

    2020  Volume 28, Issue 1, Page(s) 30–39

    Abstract: Both the A194T and a quadruple mutation CYEI (S106C, H126Y, D134E and L269I) in hepatitis B virus (HBV) polymerase reverse transcriptase domain (pol/RT) are suggested to be associated with treatment failure with tenofovir disoproxil fumarate (TDF). To ... ...

    Abstract Both the A194T and a quadruple mutation CYEI (S106C, H126Y, D134E and L269I) in hepatitis B virus (HBV) polymerase reverse transcriptase domain (pol/RT) are suggested to be associated with treatment failure with tenofovir disoproxil fumarate (TDF). To further evaluate this assertion, the prevalence of these mutations at baseline as well as their development and/or loss during TDF and tenofovir alafenamide (TAF) treatment was analysed in 3886 patients enrolled in Gilead HBV clinical studies. In total, six out of 3886 (0.2%) patients carried the rtA194T mutation, while only 1 patient carried a triple CYE and 2 patients carried a quadruple CYEI mutation at baseline. All the patients harbouring rtA194T or CYE/CYEI at baseline achieved viral suppression by week 96 after TDF or TAF treatment. No patients developed an rtA194T mutation or > 1 substitution of CYEI, and the number of patients losing any substitutions of CYEI (n = 17) was similar to the number who developed a single substitution of CYEI (n = 32) during treatment. Phenotypic evaluation of the site-directed mutant (SDM) panel containing these mutations with or without other resistance mutations did not demonstrate a significant shift in TFV and TAF potency in vitro. No evidence of rtA194T and CYEI conferring resistance to TDF or TAF was observed based on the treatment responses to TDF or TAF in patients with mutations at baseline, the lack of selection of mutations after starting TDF or TAF treatment and no change in susceptibility to TFV or TAF in vitro.
    MeSH term(s) Alanine ; Drug Resistance, Viral/genetics ; Hepatitis B virus/genetics ; Humans ; Mutation ; Tenofovir/analogs & derivatives ; Tenofovir/therapeutic use
    Chemical Substances Tenofovir (99YXE507IL) ; tenofovir alafenamide (EL9943AG5J) ; Alanine (OF5P57N2ZX)
    Language English
    Publishing date 2020-09-24
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1212497-7
    ISSN 1365-2893 ; 1352-0504
    ISSN (online) 1365-2893
    ISSN 1352-0504
    DOI 10.1111/jvh.13397
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  7. Article: Sedimentary record of ice divide migration and ice streams in the Keewatin core region of the Laurentide Ice Sheet

    Hodder, Tyler J / John Menzies / Martin Ross

    Sedimentary geology. 2016 June 01, v. 338

    2016  

    Abstract: The Aberdeen Lake region of central mainland Nunavut is a former core region of the Laurentide Ice Sheet that is characterized by streamlined glacial landforms classified into multiple crosscutting flow sets and near continuous till blanket. The presence ...

    Abstract The Aberdeen Lake region of central mainland Nunavut is a former core region of the Laurentide Ice Sheet that is characterized by streamlined glacial landforms classified into multiple crosscutting flow sets and near continuous till blanket. The presence of widespread till near the centre of the Keewatin Ice Dome raises questions about its origin. Detailed drillcore logging revealed a complex stratigraphy consisting of at least 6 till units, variably preserved across the study area. Till provenance analysis indicates deposition by near opposite-trending ice flow phases, interpreted as evidence of reconfiguration of the Keewatin Ice Divide. At the surface, large north–northwesterly aligned landforms are present across the study area. The till stratigraphy within these landforms indicates the same NNW ice flow phase is responsible for considerable till production. This ice flow phase is also correlated to a long regional dispersal train of erratics toward the Gulf of Boothia. The production of an extensive, thick (~12m), till sheet during the NNW-trending ice flow phase occurred far from the ice margin at a time of extensive ice cover of mainland Nunavut, likely from an east–west oriented ice divide. A deglacial westerly trending ice flow phase formed small drumlins atop the larger NNW streamlined till ridges and deposited a surficial till unit that is too thin to mask the NNW flow set across the study area. It is proposed that the Boothia paleo-ice stream catchment area propagated deep into the Laurentide Ice Sheet and contributed to significant till production in this core region of the Keewatin Sector prior to the westerly ice flow shift. The apparent relationship between till thickness and the size of the associated or correlated drumlins, flow sets, and dispersal trains indicates complex erosion/deposition interplay is involved in the formation of streamlined subglacial landforms.
    Keywords glaciation ; glaciers ; ice ; lakes ; logging ; provenance ; stratigraphy ; streams ; watersheds ; Nunavut
    Language English
    Dates of publication 2016-0601
    Size p. 97-114.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 216739-6
    ISSN 0037-0738
    ISSN 0037-0738
    DOI 10.1016/j.sedgeo.2016.01.001
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  8. Article ; Online: SARS-CoV-2 public health investigation in an aged care facility and challenges with serological screening in low pre-test probability settings.

    Smoll, Nicolas R / Taylor, Carmel / Martin, Ross / Wheatley, Sarah / Moore, Peter / Finger, Mitchell / Moore, Frederick / Schlebusch, Sanmarié / Khandaker, Gulam

    Communicable diseases intelligence (2018)

    2021  Volume 45

    MeSH term(s) Aged ; Antibodies, Viral/blood ; Antibody Specificity ; Antigens, Viral/immunology ; COVID-19/epidemiology ; COVID-19/virology ; COVID-19 Testing ; Female ; Homes for the Aged ; Humans ; Immunoassay/methods ; Immunoglobulin G/blood ; Male ; Microspheres ; Prevalence ; Public Health ; Queensland/epidemiology ; SARS-CoV-2 ; Serologic Tests
    Chemical Substances Antibodies, Viral ; Antigens, Viral ; Immunoglobulin G
    Language English
    Publishing date 2021-08-16
    Publishing country Australia
    Document type Journal Article
    ISSN 2209-6051
    ISSN (online) 2209-6051
    DOI 10.33321/cdi.2021.45.42
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Brief Report: Bictegravir/Emtricitabine/Tenofovir Alafenamide Efficacy in Participants With Preexisting Primary Integrase Inhibitor Resistance Through 48 Weeks of Phase 3 Clinical Trials.

    D'Antoni, Michelle L / Andreatta, Kristen / Acosta, Rima / Martin, Hal / Chang, Silvia / Martin, Ross / White, Kirsten L

    Journal of acquired immune deficiency syndromes (1999)

    2021  Volume 89, Issue 4, Page(s) 433–440

    Abstract: Background: Preexisting drug resistance limits the utility of HIV antiretroviral therapy. Studies have demonstrated safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), including in patients with M184V/I substitutions.: ... ...

    Abstract Background: Preexisting drug resistance limits the utility of HIV antiretroviral therapy. Studies have demonstrated safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), including in patients with M184V/I substitutions.
    Setting: We investigated virologic outcomes through 48 weeks of B/F/TAF treatment in individuals with preexisting primary integrase strand transfer inhibitor resistance (INSTI-R).
    Methods: Preexisting INSTI-R was retrospectively evaluated from 7 B/F/TAF studies. INSTI-R was assessed by historical genotypes and/or baseline RNA or DNA sequencing. Viral loads were measured at all visits.
    Results: Preexisting primary INSTI-R substitutions were detected in 20 of the 1907 participants (1.0%). The 20 participants were predominantly male (75%), were Black (65%), had HIV-1 subtype B (85%), and had baseline median CD4 counts of 594 cells/mm3 and median age of 52 years. Most of the participants (n = 19) were virologically suppressed at baseline and had one primary INSTI-R substitution, E92G, Y143C/H, S147G, Q148H/K/R, N155S, or R263K, +/-secondary substitutions. All suppressed participants maintained virologic suppression throughout 48 weeks without any viral blips. One treatment-naive participant had virus with Q148H+G140S that was fully sensitive to bictegravir but only partially to dolutegravir (phenotype <2.5-fold change and >4-fold change, respectively). With a baseline viral load of 30,000 copies/mL, this participant was virologically suppressed by week 4 and maintained <50 copies/mL through week 48.
    Conclusions: This small cohort with primary INSTI-R achieved and/or maintained virologic suppression through 48 weeks of B/F/TAF treatment. Consistent with the potent in vitro activity of bictegravir against most INSTI-R patterns, B/F/TAF may be a potential treatment option for patients with select preexisting INSTI-R, if confirmed by further studies.
    MeSH term(s) Alanine ; Amides ; Anti-HIV Agents/therapeutic use ; Emtricitabine/therapeutic use ; HIV Infections/drug therapy ; HIV Integrase Inhibitors/therapeutic use ; Heterocyclic Compounds, 3-Ring/pharmacology ; Heterocyclic Compounds, 3-Ring/therapeutic use ; Humans ; Male ; Middle Aged ; Piperazines ; Pyridones/therapeutic use ; Retrospective Studies ; Tenofovir/analogs & derivatives
    Chemical Substances Amides ; Anti-HIV Agents ; HIV Integrase Inhibitors ; Heterocyclic Compounds, 3-Ring ; Piperazines ; Pyridones ; bictegravir (8GB79LOJ07) ; Tenofovir (99YXE507IL) ; tenofovir alafenamide (EL9943AG5J) ; Emtricitabine (G70B4ETF4S) ; Alanine (OF5P57N2ZX)
    Language English
    Publishing date 2021-12-06
    Publishing country United States
    Document type Clinical Trial, Phase III ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 645053-2
    ISSN 1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
    ISSN (online) 1944-7884 ; 1077-9450
    ISSN 0897-5965 ; 0894-9255 ; 1525-4135
    DOI 10.1097/QAI.0000000000002888
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) From Dolutegravir (DTG)+F/TAF or DTG+F/Tenofovir Disoproxil Fumarate (TDF) in the Presence of Pre-existing NRTI Resistance.

    Acosta, Rima K / Willkom, Madeleine / Andreatta, Kristen / Liu, Hui / Martin, Ross / Parvangada, Aiyappa / Martin, Hal / Collins, Sean / White, Kirsten L

    Journal of acquired immune deficiency syndromes (1999)

    2021  Volume 85, Issue 3, Page(s) 363–371

    Abstract: Background: Study 4030 was a phase 3, randomized, double-blinded study of 565 HIV-1 RNA-suppressed participants switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)+F/TAF. Nucleoside reverse transcriptase ... ...

    Abstract Background: Study 4030 was a phase 3, randomized, double-blinded study of 565 HIV-1 RNA-suppressed participants switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)+F/TAF. Nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI, and protease inhibitor resistance (-R) was allowed, but integrase strand transfer inhibitor-R was excluded. Here, we describe the detailed resistance analysis.
    Methods: Historical plasma HIV-1 RNA genotypes and baseline proviral DNA genotypes were analyzed. Documented or investigator-suspected NRTI-R was grouped for stratification into 3 categories of level of resistance. Viral blips were assessed through week 48. Virologic failures had genotypic and phenotypic resistance analyses at week 48, confirmed failure, or last visit, if HIV-1 RNA did not resuppress to <50 copies/mL while on study drug.
    Results: In total, 83% (470/565) of participants had baseline genotypic data available with NRTI-R detected in 24% (138/565), including 5% (30/565) with K65R/E/N or ≥3 thymidine analog mutations and 19% (108/565) with other NRTI-R mutations. M184V/I was present in 14% (81/565). Pre-existing integrase strand transfer inhibitor-R mutations were found in 4% (20/565) of participants. Primary non-NRTI-R and protease inhibitor-R mutations were present in 21% (118/565) and 7% (38/565) of participants. High rates of viral suppression were maintained in all groups through week 48; blips were observed in only 15 participants (2.7%). Three participants met criteria for resistance analysis (all in DTG+F/TAF arm); none developed treatment-emergent resistance to study drugs.
    Conclusions: Participants with baseline NRTI resistance, much of which was previously undocumented, maintained suppression 48 weeks after switching to B/F/TAF or DTG+F/TAF triple therapy. Blips and virologic failure were uncommon using either regimen, with no treatment-emergent resistance.
    MeSH term(s) Adenine/administration & dosage ; Adenine/analogs & derivatives ; Adenine/therapeutic use ; Anti-HIV Agents/administration & dosage ; Anti-HIV Agents/therapeutic use ; Double-Blind Method ; Emtricitabine/administration & dosage ; Emtricitabine/therapeutic use ; HIV Infections/drug therapy ; HIV-1/drug effects ; HIV-1/genetics ; Heterocyclic Compounds, 3-Ring/administration & dosage ; Heterocyclic Compounds, 3-Ring/therapeutic use ; Heterocyclic Compounds, 4 or More Rings/administration & dosage ; Heterocyclic Compounds, 4 or More Rings/therapeutic use ; Humans ; Logistic Models ; Multivariate Analysis ; Oxazines/administration & dosage ; Oxazines/therapeutic use ; Piperazines/administration & dosage ; Piperazines/therapeutic use ; Pyridones/administration & dosage ; Pyridones/therapeutic use ; RNA, Viral/genetics ; Tenofovir/administration & dosage ; Tenofovir/therapeutic use
    Chemical Substances Anti-HIV Agents ; Heterocyclic Compounds, 3-Ring ; Heterocyclic Compounds, 4 or More Rings ; Oxazines ; Piperazines ; Pyridones ; RNA, Viral ; emtricitabine tenofovir alafenamide ; bictegravir (8GB79LOJ07) ; Tenofovir (99YXE507IL) ; dolutegravir (DKO1W9H7M1) ; Emtricitabine (G70B4ETF4S) ; Adenine (JAC85A2161)
    Language English
    Publishing date 2021-06-04
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Randomized Controlled Trial
    ZDB-ID 645053-2
    ISSN 1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
    ISSN (online) 1944-7884 ; 1077-9450
    ISSN 0897-5965 ; 0894-9255 ; 1525-4135
    DOI 10.1097/QAI.0000000000002454
    Database MEDical Literature Analysis and Retrieval System OnLINE

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