Longer-term virologic outcomes on tenofovir-lamivudine-dolutegravir in second-line ART
Background: Dolutegravir in second-line antiretroviral therapy (ART) is more effective with recycled tenofovir than switching to zidovudine. However, dolutegravir resistance is more frequent in second-line compared to first-line ART. Objectives: We report long-term virologic outcomes from a clinica...
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AOSIS
2025-04-01
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| Series: | Southern African Journal of HIV Medicine |
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| Online Access: | https://sajhivmed.org.za/index.php/hivmed/article/view/1677 |
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| author | Jennifer K. van Heerden Ying Zhao Claire M. Keene Rulan Griesel Zaayid Omar René Goliath Kayla Delaney Gert van Zyl Gary Maartens Graeme Meintjes |
| author_facet | Jennifer K. van Heerden Ying Zhao Claire M. Keene Rulan Griesel Zaayid Omar René Goliath Kayla Delaney Gert van Zyl Gary Maartens Graeme Meintjes |
| author_sort | Jennifer K. van Heerden |
| collection | DOAJ |
| description | Background: Dolutegravir in second-line antiretroviral therapy (ART) is more effective with recycled tenofovir than switching to zidovudine. However, dolutegravir resistance is more frequent in second-line compared to first-line ART.
Objectives: We report long-term virologic outcomes from a clinical trial.
Method: AntiRetroviral Therapy In Second-line: investigating Tenofovir-lamivudine-dolutegravir (ARTIST) was a randomised, double-blind, phase II clinical trial. Eligible participants had two consecutive HIV-1 RNA ≥ 1000 copies/mL on first-line ART, mostly tenofovir-emtricitabine-efavirenz. Participants were switched to tenofovir-lamivudine-dolutegravir (TLD) with lead-in 50 mg dolutegravir twice daily in stage one (n = 62), and randomised to TLD with additional lead-in 50 mg dolutegravir or placebo for the first 14 days in stage two (n = 130). We present results up to 158 weeks, combining stages one and two.
Results: We enrolled 192 participants: 127/176 (72%) had resistance (Stanford score ≥ 15) to both tenofovir and lamivudine. At week 48, 151/186 (81%; 95% confidence interval [CI] 75%, 87%) had HIV-1 RNA 50 copies/mL. Of 127 participants with follow-up through week 158, 78% (95% CI 70%, 85%) maintained HIV-1 RNA 50 copies/mL, 11% had HIV-1 RNA 50–999 copies/mL, and 11% had HIV-1 RNA ≥ 1000 copies/mL. Twenty-nine participants met criteria for resistance testing: one developed intermediate-level dolutegravir resistance (G118R mutation) at week 96, and one had high-level dolutegravir resistance (E138K, G118R, G163R, T66A mutations) detected at week 146.
Conclusion: Among adults switching to TLD with detectable HIV-1 RNA and substantial tenofovir and lamivudine resistance, a high proportion maintained virologic suppression up to 158 weeks. Emergent dolutegravir resistance occurred in ~1% of participants after 2–3 years on second-line TLD. |
| format | Article |
| id | doaj-art-cfc5f41604f740ca8ec4e4243d297423 |
| institution | Kabale University |
| issn | 1608-9693 2078-6751 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | AOSIS |
| record_format | Article |
| series | Southern African Journal of HIV Medicine |
| spelling | doaj-art-cfc5f41604f740ca8ec4e4243d2974232025-08-20T03:53:06ZengAOSISSouthern African Journal of HIV Medicine1608-96932078-67512025-04-01261e1e1210.4102/sajhivmed.v26i1.1677906Longer-term virologic outcomes on tenofovir-lamivudine-dolutegravir in second-line ARTJennifer K. van Heerden0Ying Zhao1Claire M. Keene2Rulan Griesel3Zaayid Omar4René Goliath5Kayla Delaney6Gert van Zyl7Gary Maartens8Graeme Meintjes9Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; and Department of Biochemistry, Medical Sciences Division, University of Oxford, OxfordWellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; and Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape TownMédecins Sans Frontières, Cape Town, South Africa; and Health Systems Collaborative, NDM Centre for Global Health Research, Nuffield Department of Medicine, University of Oxford, OxfordWellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; and Division of Clinical Pharmacology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape TownWellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape TownWellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape TownDivision of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape TownDivision of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape TownWellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; and Division of Clinical Pharmacology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape TownWellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Department of Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa; and Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, LondonBackground: Dolutegravir in second-line antiretroviral therapy (ART) is more effective with recycled tenofovir than switching to zidovudine. However, dolutegravir resistance is more frequent in second-line compared to first-line ART. Objectives: We report long-term virologic outcomes from a clinical trial. Method: AntiRetroviral Therapy In Second-line: investigating Tenofovir-lamivudine-dolutegravir (ARTIST) was a randomised, double-blind, phase II clinical trial. Eligible participants had two consecutive HIV-1 RNA ≥ 1000 copies/mL on first-line ART, mostly tenofovir-emtricitabine-efavirenz. Participants were switched to tenofovir-lamivudine-dolutegravir (TLD) with lead-in 50 mg dolutegravir twice daily in stage one (n = 62), and randomised to TLD with additional lead-in 50 mg dolutegravir or placebo for the first 14 days in stage two (n = 130). We present results up to 158 weeks, combining stages one and two. Results: We enrolled 192 participants: 127/176 (72%) had resistance (Stanford score ≥ 15) to both tenofovir and lamivudine. At week 48, 151/186 (81%; 95% confidence interval [CI] 75%, 87%) had HIV-1 RNA 50 copies/mL. Of 127 participants with follow-up through week 158, 78% (95% CI 70%, 85%) maintained HIV-1 RNA 50 copies/mL, 11% had HIV-1 RNA 50–999 copies/mL, and 11% had HIV-1 RNA ≥ 1000 copies/mL. Twenty-nine participants met criteria for resistance testing: one developed intermediate-level dolutegravir resistance (G118R mutation) at week 96, and one had high-level dolutegravir resistance (E138K, G118R, G163R, T66A mutations) detected at week 146. Conclusion: Among adults switching to TLD with detectable HIV-1 RNA and substantial tenofovir and lamivudine resistance, a high proportion maintained virologic suppression up to 158 weeks. Emergent dolutegravir resistance occurred in ~1% of participants after 2–3 years on second-line TLD.https://sajhivmed.org.za/index.php/hivmed/article/view/1677hivtenofovir-lamivudine-dolutegravirdolutegravirdrug resistancesecond-linesouth africa |
| spellingShingle | Jennifer K. van Heerden Ying Zhao Claire M. Keene Rulan Griesel Zaayid Omar René Goliath Kayla Delaney Gert van Zyl Gary Maartens Graeme Meintjes Longer-term virologic outcomes on tenofovir-lamivudine-dolutegravir in second-line ART Southern African Journal of HIV Medicine hiv tenofovir-lamivudine-dolutegravir dolutegravir drug resistance second-line south africa |
| title | Longer-term virologic outcomes on tenofovir-lamivudine-dolutegravir in second-line ART |
| title_full | Longer-term virologic outcomes on tenofovir-lamivudine-dolutegravir in second-line ART |
| title_fullStr | Longer-term virologic outcomes on tenofovir-lamivudine-dolutegravir in second-line ART |
| title_full_unstemmed | Longer-term virologic outcomes on tenofovir-lamivudine-dolutegravir in second-line ART |
| title_short | Longer-term virologic outcomes on tenofovir-lamivudine-dolutegravir in second-line ART |
| title_sort | longer term virologic outcomes on tenofovir lamivudine dolutegravir in second line art |
| topic | hiv tenofovir-lamivudine-dolutegravir dolutegravir drug resistance second-line south africa |
| url | https://sajhivmed.org.za/index.php/hivmed/article/view/1677 |
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