Marie-Angélique De Scheerder, Sophie Degroote, Mareva Delporte, Maja Kiselinova, Wim Trypsteen, Lara Vincke, Evelien De Smet, Bram Van Den Eeckhout, Loïc Schrooyen, Maxime Verschoore, Camilla Muccini, Sophie Vanherrewege, Els Caluwe, Stefanie De Buyser, Sarah Gerlo, Evy Blomme, Linos Vandekerckhove
{"title":"在一项第四阶段随机对照转换试验（RUMBA）中，对艾滋病毒储库的深入分析证实了 DTG/3TC 的有效性和安全性。","authors":"Marie-Angélique De Scheerder, Sophie Degroote, Mareva Delporte, Maja Kiselinova, Wim Trypsteen, Lara Vincke, Evelien De Smet, Bram Van Den Eeckhout, Loïc Schrooyen, Maxime Verschoore, Camilla Muccini, Sophie Vanherrewege, Els Caluwe, Stefanie De Buyser, Sarah Gerlo, Evy Blomme, Linos Vandekerckhove","doi":"10.1093/infdis/jiae405","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Reducing the number of active compounds for lifelong human immunodeficiency virus (HIV) treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control support the robustness and safety of 2DR (2-drug regimen) antiretroviral therapy compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts, and sustained immunological control.</p><p><strong>Methods: </strong>The RUMBA study is the first prospective randomized controlled trial evaluating the impact of switch from 3DR to 2DR on the viral reservoir. Participants on any stable second-generation integrase strand transfer inhibitor-based 3DR regimen with HIV-1 RNA < 50 copies/mL plasma for at least 3 months were randomized to switch to dolutegravir/lamivudine (DTG/3TC, n = 89) or to switch or stay on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, n = 45). After 48 weeks, virological, immunological, and metabolic parameters were evaluated.</p><p><strong>Results: </strong>We did not observe a significant difference in change over time in the mean number of intact HIV-1 DNA copies/million CD4+ T cells with DTG/3TC compared to B/F/TAF. There was no evidence in this study that switching to DTG/3TC increased the active reservoir by HIV-1 transcription. No significant changes in proinflammatory cytokines or major immune cell subsets were observed. Changes in exhaustion and activation of specific cellular subsets were small and bidirectional. Metabolic outcomes are similar between the treatment regimens.</p><p><strong>Conclusions: </strong>This study confirms the safety of DTG/3TC compared to B/F/TAF through viral control after in-depth investigations of the intact HIV-1 reservoir, HIV-1 transcription, and inflammatory markers.</p><p><strong>Clinical trials registration: </strong>NCT04553081.</p>","PeriodicalId":50179,"journal":{"name":"Journal of Infectious Diseases","volume":" ","pages":"e91-e100"},"PeriodicalIF":5.0000,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793038/pdf/","citationCount":"0","resultStr":"{\"title\":\"In-depth Analysis of the HIV Reservoir Confirms Effectiveness and Safety of Dolutegravir/Lamivudine in a Phase 4 Randomized Controlled Switch Trial (RUMBA).\",\"authors\":\"Marie-Angélique De Scheerder, Sophie Degroote, Mareva Delporte, Maja Kiselinova, Wim Trypsteen, Lara Vincke, Evelien De Smet, Bram Van Den Eeckhout, Loïc Schrooyen, Maxime Verschoore, Camilla Muccini, Sophie Vanherrewege, Els Caluwe, Stefanie De Buyser, Sarah Gerlo, Evy Blomme, Linos Vandekerckhove\",\"doi\":\"10.1093/infdis/jiae405\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Reducing the number of active compounds for lifelong human immunodeficiency virus (HIV) treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control support the robustness and safety of 2DR (2-drug regimen) antiretroviral therapy compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts, and sustained immunological control.</p><p><strong>Methods: </strong>The RUMBA study is the first prospective randomized controlled trial evaluating the impact of switch from 3DR to 2DR on the viral reservoir. Participants on any stable second-generation integrase strand transfer inhibitor-based 3DR regimen with HIV-1 RNA < 50 copies/mL plasma for at least 3 months were randomized to switch to dolutegravir/lamivudine (DTG/3TC, n = 89) or to switch or stay on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, n = 45). After 48 weeks, virological, immunological, and metabolic parameters were evaluated.</p><p><strong>Results: </strong>We did not observe a significant difference in change over time in the mean number of intact HIV-1 DNA copies/million CD4+ T cells with DTG/3TC compared to B/F/TAF. There was no evidence in this study that switching to DTG/3TC increased the active reservoir by HIV-1 transcription. No significant changes in proinflammatory cytokines or major immune cell subsets were observed. Changes in exhaustion and activation of specific cellular subsets were small and bidirectional. Metabolic outcomes are similar between the treatment regimens.</p><p><strong>Conclusions: </strong>This study confirms the safety of DTG/3TC compared to B/F/TAF through viral control after in-depth investigations of the intact HIV-1 reservoir, HIV-1 transcription, and inflammatory markers.</p><p><strong>Clinical trials registration: </strong>NCT04553081.</p>\",\"PeriodicalId\":50179,\"journal\":{\"name\":\"Journal of Infectious Diseases\",\"volume\":\" \",\"pages\":\"e91-e100\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2025-02-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793038/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/infdis/jiae405\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/infdis/jiae405","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
In-depth Analysis of the HIV Reservoir Confirms Effectiveness and Safety of Dolutegravir/Lamivudine in a Phase 4 Randomized Controlled Switch Trial (RUMBA).
Background: Reducing the number of active compounds for lifelong human immunodeficiency virus (HIV) treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control support the robustness and safety of 2DR (2-drug regimen) antiretroviral therapy compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts, and sustained immunological control.
Methods: The RUMBA study is the first prospective randomized controlled trial evaluating the impact of switch from 3DR to 2DR on the viral reservoir. Participants on any stable second-generation integrase strand transfer inhibitor-based 3DR regimen with HIV-1 RNA < 50 copies/mL plasma for at least 3 months were randomized to switch to dolutegravir/lamivudine (DTG/3TC, n = 89) or to switch or stay on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, n = 45). After 48 weeks, virological, immunological, and metabolic parameters were evaluated.
Results: We did not observe a significant difference in change over time in the mean number of intact HIV-1 DNA copies/million CD4+ T cells with DTG/3TC compared to B/F/TAF. There was no evidence in this study that switching to DTG/3TC increased the active reservoir by HIV-1 transcription. No significant changes in proinflammatory cytokines or major immune cell subsets were observed. Changes in exhaustion and activation of specific cellular subsets were small and bidirectional. Metabolic outcomes are similar between the treatment regimens.
Conclusions: This study confirms the safety of DTG/3TC compared to B/F/TAF through viral control after in-depth investigations of the intact HIV-1 reservoir, HIV-1 transcription, and inflammatory markers.
期刊介绍：
Published continuously since 1904, The Journal of Infectious Diseases (JID) is the premier global journal for original research on infectious diseases. The editors welcome Major Articles and Brief Reports describing research results on microbiology, immunology, epidemiology, and related disciplines, on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune responses. JID is an official publication of the Infectious Diseases Society of America.
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