Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line in adults failing a tenofovir-based first-line regimen. Keene, C. M, Griesel, R., Zhao, Y., Gcwabe, Z., Sayed, K., Hill, A., Cassidy, T., Ngwenya, O., Jackson, A., van Zyl, G., Schutz, C., Goliath, R., Flowers, T., Goemaere, E., Wiesner, L., Simmons, B., Maartens, G., & Meintjes, G. A AIDS, 35(9):1423–1432, 2021. ![Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line in adults failing a tenofovir-based first-line regimen [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Objective: Recycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir would provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized nucleoside reverse transcriptase inhibitor (NRTI) backbone. We evaluated efficacy of tenofovir/lamivudine/dolutegravir (TLD) in patients failing first-line tenofovir/XTC/efavirenz or nevirapine. Design: Single arm, prospective, interventional study Setting: Two primary care clinics in Khayelitsha, South Africa Participants: 60 adult patients with two viral loads (VL)\textgreater1000 copies/mL Intervention: Participants were switched to TLD with additional dolutegravir (50 mg) for two weeks to overcome efavirenz induction. Primary outcome: Proportion achieving VL\textless50 copies/mL at week 24 using the FDA snapshot algorithm. Results: Baseline median CD4 count was 248 cells/mm3, VL 10580 copies/mL and 48/54 (89%) had resistance (Stanford score ≥15) to one or both of tenofovir and XTC. No participants were lost to follow-up. At week 24, 51/60 (85%, 95% CI 73–93%) were virologically suppressed, six had VL 50–100 copies/mL, one VL 100–1000 copies/mL, one no VL in window, and one switched due to tenofovir-related adverse event. No integrase mutations were detected in the one participant meeting criteria for resistance testing. Virological suppression was achieved by 29/35 (83%, 95% CI 66–93%) with resistance to tenofovir and XTC, 11/13 (85%, 95% CI 55–98%) with resistance to XTC, and 6/6 (100%, 95% CI 54–100%) with resistance to neither. Conclusion: A high proportion of adults switching to second-line TLD achieved virologic suppression despite substantial baseline NRTI resistance and most not suppressed had low-level viraemia (≤100 copies/mL). This suggests recycling tenofovir and XTC with dolutegravir could provide an effective second-line option. Correspondence to Claire M. Keene, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. Tel: +447756770927; e-mail: claire.keene@ndm.ox.ac.uk Received 28 January, 2021 Revised 10 April, 2021 Accepted 13 April, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright © 2021 Wolters Kluwer Health, Inc.
@article{Keene9000,
abstract = {Objective: Recycling tenofovir and lamivudine/emtricitabine (XTC) with dolutegravir would provide a more tolerable, affordable, and scalable second-line regimen than dolutegravir with an optimized nucleoside reverse transcriptase inhibitor (NRTI) backbone. We evaluated efficacy of tenofovir/lamivudine/dolutegravir (TLD) in patients failing first-line tenofovir/XTC/efavirenz or nevirapine. Design: Single arm, prospective, interventional study Setting: Two primary care clinics in Khayelitsha, South Africa Participants: 60 adult patients with two viral loads (VL){\textgreater}1000 copies/mL Intervention: Participants were switched to TLD with additional dolutegravir (50 mg) for two weeks to overcome efavirenz induction. Primary outcome: Proportion achieving VL{\textless}50 copies/mL at week 24 using the FDA snapshot algorithm. Results: Baseline median CD4 count was 248 cells/mm3, VL 10580 copies/mL and 48/54 (89{\%}) had resistance (Stanford score ≥15) to one or both of tenofovir and XTC. No participants were lost to follow-up. At week 24, 51/60 (85{\%}, 95{\%} CI 73–93{\%}) were virologically suppressed, six had VL 50–100 copies/mL, one VL 100–1000 copies/mL, one no VL in window, and one switched due to tenofovir-related adverse event. No integrase mutations were detected in the one participant meeting criteria for resistance testing. Virological suppression was achieved by 29/35 (83{\%}, 95{\%} CI 66–93{\%}) with resistance to tenofovir and XTC, 11/13 (85{\%}, 95{\%} CI 55–98{\%}) with resistance to XTC, and 6/6 (100{\%}, 95{\%} CI 54–100{\%}) with resistance to neither. Conclusion: A high proportion of adults switching to second-line TLD achieved virologic suppression despite substantial baseline NRTI resistance and most not suppressed had low-level viraemia (≤100 copies/mL). This suggests recycling tenofovir and XTC with dolutegravir could provide an effective second-line option. Correspondence to Claire M. Keene, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. Tel: +447756770927; e-mail: claire.keene@ndm.ox.ac.uk Received 28 January, 2021 Revised 10 April, 2021 Accepted 13 April, 2021 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). Copyright {\textcopyright} 2021 Wolters Kluwer Health, Inc.},
author = {Keene, Claire M and Griesel, Rulan and Zhao, Ying and Gcwabe, Zimasa and Sayed, Kaneez and Hill, Andrew and Cassidy, Tali and Ngwenya, Olina and Jackson, Amanda and van Zyl, Gert and Schutz, Charlotte and Goliath, Rene and Flowers, Tracy and Goemaere, Eric and Wiesner, Lubbe and Simmons, Bryony and Maartens, Gary and Meintjes, Graeme A},
doi = {10.1097/QAD.0000000000002936},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Keene et al. - 2021 - Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line in adults failing a tenofovir-based fi.pdf:pdf;:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Keene et al. - 2021 - Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line in adults failing a tenofovir-based(2).pdf:pdf},
issn = {0269-9370},
journal = {AIDS},
keywords = {HIV,OA,antiretroviral therapy,dolutegravir,fund{\_}ack,original,second-line},
mendeley-tags = {OA,fund{\_}ack,original},
number = {9},
pages = {1423--1432},
pmid = {33973876},
title = {{Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line in adults failing a tenofovir-based first-line regimen}},
url = {https://journals.lww.com/aidsonline/Fulltext/9000/Virologic{\_}efficacy{\_}of{\_}tenofovir,{\_}lamivudine{\_}and.96409.aspx},
volume = {35},
year = {2021}
}
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Design: Single arm, prospective, interventional study Setting: Two primary care clinics in Khayelitsha, South Africa Participants: 60 adult patients with two viral loads (VL)\\textgreater1000 copies/mL Intervention: Participants were switched to TLD with additional dolutegravir (50 mg) for two weeks to overcome efavirenz induction. Primary outcome: Proportion achieving VL\\textless50 copies/mL at week 24 using the FDA snapshot algorithm. Results: Baseline median CD4 count was 248 cells/mm3, VL 10580 copies/mL and 48/54 (89%) had resistance (Stanford score ≥15) to one or both of tenofovir and XTC. No participants were lost to follow-up. At week 24, 51/60 (85%, 95% CI 73–93%) were virologically suppressed, six had VL 50–100 copies/mL, one VL 100–1000 copies/mL, one no VL in window, and one switched due to tenofovir-related adverse event. No integrase mutations were detected in the one participant meeting criteria for resistance testing. Virological suppression was achieved by 29/35 (83%, 95% CI 66–93%) with resistance to tenofovir and XTC, 11/13 (85%, 95% CI 55–98%) with resistance to XTC, and 6/6 (100%, 95% CI 54–100%) with resistance to neither. Conclusion: A high proportion of adults switching to second-line TLD achieved virologic suppression despite substantial baseline NRTI resistance and most not suppressed had low-level viraemia (≤100 copies/mL). This suggests recycling tenofovir and XTC with dolutegravir could provide an effective second-line option. Correspondence to Claire M. Keene, Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. Tel: +447756770927; e-mail: claire.keene@ndm.ox.ac.uk Received 28 January, 2021 Revised 10 April, 2021 Accepted 13 April, 2021 Supplemental digital content is available for this article. 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