دورية أكاديمية
Low-dose ritonavir-boosted darunavir once daily versus ritonavir-boosted lopinavir for participants with less than 50 HIV RNA copies per mL (WRHI 052): a randomised, open-label, phase 3, non-inferiority trial.
| العنوان: | Low-dose ritonavir-boosted darunavir once daily versus ritonavir-boosted lopinavir for participants with less than 50 HIV RNA copies per mL (WRHI 052): a randomised, open-label, phase 3, non-inferiority trial. |
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| المؤلفون: | Venter WDF; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: fventer@wrhi.ac.za., Moorhouse M; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Sokhela S; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Serenata C; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Akpomiemie G; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Qavi A; Faculty of Medicine, Imperial College London, London, UK., Mashabane N; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Arulappan N; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Sim JW; Faculty of Medicine, Imperial College London, London, UK., Sinxadi PZ; Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Wiesner L; Division of Clinical Pharmacology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa., Maharaj E; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Wallis C; BARC, Lancet Laboratories, Johannesburg, South Africa., Boyles T; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Ripin D; Clinton Health Access Initiative, Boston, MA, USA., Stacey S; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Division of Infectious Diseases, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa., Chitauri G; Division of Infectious Diseases, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa., Hill A; Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK. |
| المصدر: | The lancet. HIV [Lancet HIV] 2019 Jul; Vol. 6 (7), pp. e428-e437. Date of Electronic Publication: 2019 Jun 12. |
| نوع المنشور: | Clinical Trial, Phase III; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101645355 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2352-3018 (Electronic) Linking ISSN: 23523018 NLM ISO Abbreviation: Lancet HIV Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier B.V., [2014]- |
| مواضيع طبية MeSH: | Antiretroviral Therapy, Highly Active*/methods , Viral Load*, Anti-HIV Agents/*therapeutic use , HIV Infections/*drug therapy , HIV Infections/*virology , HIV-1/*drug effects, Adult ; Aged ; Anti-HIV Agents/administration & dosage ; CD4 Lymphocyte Count ; Darunavir/administration & dosage ; Drug Resistance, Viral ; Female ; HIV Infections/immunology ; HIV-1/immunology ; Humans ; Lopinavir/administration & dosage ; Male ; Middle Aged ; Ritonavir/administration & dosage ; Treatment Outcome |
| مستخلص: | Background: Pilot studies suggest that ritonavir-boosted darunavir could show high efficacy at doses below those currently approved. We investigated whether switch to 400 mg of darunavir boosted with 100 mg ritonavir once daily could show equivalent efficacy to continuation of ritonavir-boosted lopinavir (a protease inhibitor commonly used in low-income and middle-income countries) for individuals with HIV RNA suppression. Methods: In the WRHI 052 study, a randomised, parallel-group, open-label, non-inferiority phase 3 trial, adults who were HIV-1 positive were enrolled in Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa. Eligible participants were 18 years or older, who tolerated ritonavir-boosted lopinavir in combination with two nucleoside analogues (standard of care) for 6 months or more, and had plasma HIV-1 RNA of less than 50 copies per mL within 60 days of enrolment. We randomly assigned participants (1:1), using a computer-generated randomisation plan, to switch to darunavir (400 mg) boosted with ritonavir (100 mg) once daily or remain on ritonavir-boosted lopinavir (800 mg [plus 200 mg ritonavir]), with nucleoside analogues left unchanged. The primary endpoint was the proportion of patients with less than 50 HIV-1 RNA copies per mL at week 48 (US Food and Drug Administration snapshot algorithm; non-inferiority margin -4%). Primary and safety analyses included participants receiving at least one dose of darunavir boosted with ritonavir. This trial is registered with ClinicalTrials.gov, number NCT02671383. Findings: Between June 30, 2016, and June 15, 2017, 148 participants were assigned to ritonavir-boosted darunavir 400 mg and 152 continued on their lopinavir-containing regimen. Four (3%) patients in the darunavir group and three (2%) in the lopinavir group discontinued before week 48. At week 48, darunavir was non-inferior to lopinavir for the primary outcome (142 [96%] of 148 participants on darunavir had <50 HIV-1 RNA copies per mL vs 143 [94%] of 152 participants on lopinavir; difference 1·9% [95% CI -3·4 to 7·3]), with a predefined margin of -4%. More participants taking darunavir (30 [20%] participants) had drug-related adverse events than those on lopinavir (eight [5%]), but the adverse events were generally asymptomatic and resolved when switching back to lopinavir. Elevated liver transaminase in three (1%; one symptomatic) darunavir participants led to study withdrawal; all transaminase elevations resolved on restarting lopinavir. Interpretation: Low-dose ritonavir-boosted darunavir might be a safe and efficacious switch option to maintain HIV suppression for patients on lopinavir. However, an adequately powered and designed study in viraemic participants is needed. Funding: South African Medical Research Council, United States Agency for International Development, and US National Institute of Allergy and Infectious Diseases. (Copyright © 2019 Elsevier Ltd. All rights reserved.) |
| التعليقات: | Comment in: Lancet HIV. 2019 Jul;6(7):e412-e413. (PMID: 31202689) |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02671383 |
| المشرفين على المادة: | 0 (Anti-HIV Agents) 2494G1JF75 (Lopinavir) O3J8G9O825 (Ritonavir) YO603Y8113 (Darunavir) |
| تواريخ الأحداث: | Date Created: 20190617 Date Completed: 20200601 Latest Revision: 20200601 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/S2352-3018(19)30081-5 |
| PMID: | 31202690 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 2352-3018 |
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| DOI: | 10.1016/S2352-3018(19)30081-5 |