M I Figueroa, O Sued, D Cecchini, M Sanchez, M J Rolón, G Lopardo, M Ceschel, G Miernes, M Destefano, P Patterson, A Gun, V Fink, Z Ortiz, P Cahn
{"title":"基于共配型达芦那韦/利托那韦加拉米夫定的双重疗法用于艾滋病病毒感染的初始治疗:ANDES 随机对照试验。","authors":"M I Figueroa, O Sued, D Cecchini, M Sanchez, M J Rolón, G Lopardo, M Ceschel, G Miernes, M Destefano, P Patterson, A Gun, V Fink, Z Ortiz, P Cahn","doi":"10.1016/j.ijantimicag.2024.107301","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Tenofovir containing antiretroviral therapy regimens may bring long-term toxicity-related side effects. We aimed to assess the virological efficacy of co-formulated darunavir-ritonavir plus lamivudine compared to darunavir-ritonavir plus tenofovir and emtricitabine or lamivudine.</p><p><strong>Methods: </strong>The ANDES study was a 48-week, phase 4, randomized, open-label, non-inferiority trial in naïve adults living with HIV. Patients were randomized 1:1 to receive a daily oral regimen of either dual therapy based on a generic co-formulation of darunavir-ritonavir (800/100 mg) plus a generic lamivudine 300 mg pill, or triple therapy with darunavir-ritonavir plus tenofovir/emtricitabine (300/200 mg) or tenofovir/lamivudine (300/300 mg). The primary endpoint was the proportion of patients with a viral load of less than 50 copies/mL at week 48 in the intention-to-treat population. We used the FDA snapshot algorithm and a non-inferiority margin of -12%. Secondary objectives included safety analysis in the per-protocol population. This study is registered at ClinicalTrials.gov, NCT02770508.</p><p><strong>Results: </strong>Between November 2015 to October 31, 2020, 336 participants were randomly assigned either to the triple therapy arm (165) or the dual therapy arm (171). After 48 weeks, 153 patients in the triple therapy group (93%) and 155 patients in the double therapy group (91%) achieved virological suppression (difference -2·1%, 95%CI -7·0 to 2·9). Drug-related adverse events were more common in the triple therapy group (p=0·04). Two toxicity-related events led to discontinuation in each group.</p><p><strong>Interpretation: </strong>Co -formulated darunavir/ ritonavir plus lamivudine has shown non-inferiority and a safer toxicity profile compared to a standard-of-care triple regimen including tenofovir in treatment-naïve patients.</p>","PeriodicalId":13818,"journal":{"name":"International Journal of Antimicrobial Agents","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dual Therapy based on Co-formulated darunavir/ritonavir plus lamivudine for initial therapy of HIV infection: the ANDES randomized controlled trial.\",\"authors\":\"M I Figueroa, O Sued, D Cecchini, M Sanchez, M J Rolón, G Lopardo, M Ceschel, G Miernes, M Destefano, P Patterson, A Gun, V Fink, Z Ortiz, P Cahn\",\"doi\":\"10.1016/j.ijantimicag.2024.107301\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Tenofovir containing antiretroviral therapy regimens may bring long-term toxicity-related side effects. We aimed to assess the virological efficacy of co-formulated darunavir-ritonavir plus lamivudine compared to darunavir-ritonavir plus tenofovir and emtricitabine or lamivudine.</p><p><strong>Methods: </strong>The ANDES study was a 48-week, phase 4, randomized, open-label, non-inferiority trial in naïve adults living with HIV. Patients were randomized 1:1 to receive a daily oral regimen of either dual therapy based on a generic co-formulation of darunavir-ritonavir (800/100 mg) plus a generic lamivudine 300 mg pill, or triple therapy with darunavir-ritonavir plus tenofovir/emtricitabine (300/200 mg) or tenofovir/lamivudine (300/300 mg). The primary endpoint was the proportion of patients with a viral load of less than 50 copies/mL at week 48 in the intention-to-treat population. We used the FDA snapshot algorithm and a non-inferiority margin of -12%. Secondary objectives included safety analysis in the per-protocol population. This study is registered at ClinicalTrials.gov, NCT02770508.</p><p><strong>Results: </strong>Between November 2015 to October 31, 2020, 336 participants were randomly assigned either to the triple therapy arm (165) or the dual therapy arm (171). After 48 weeks, 153 patients in the triple therapy group (93%) and 155 patients in the double therapy group (91%) achieved virological suppression (difference -2·1%, 95%CI -7·0 to 2·9). Drug-related adverse events were more common in the triple therapy group (p=0·04). 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Dual Therapy based on Co-formulated darunavir/ritonavir plus lamivudine for initial therapy of HIV infection: the ANDES randomized controlled trial.
Background: Tenofovir containing antiretroviral therapy regimens may bring long-term toxicity-related side effects. We aimed to assess the virological efficacy of co-formulated darunavir-ritonavir plus lamivudine compared to darunavir-ritonavir plus tenofovir and emtricitabine or lamivudine.
Methods: The ANDES study was a 48-week, phase 4, randomized, open-label, non-inferiority trial in naïve adults living with HIV. Patients were randomized 1:1 to receive a daily oral regimen of either dual therapy based on a generic co-formulation of darunavir-ritonavir (800/100 mg) plus a generic lamivudine 300 mg pill, or triple therapy with darunavir-ritonavir plus tenofovir/emtricitabine (300/200 mg) or tenofovir/lamivudine (300/300 mg). The primary endpoint was the proportion of patients with a viral load of less than 50 copies/mL at week 48 in the intention-to-treat population. We used the FDA snapshot algorithm and a non-inferiority margin of -12%. Secondary objectives included safety analysis in the per-protocol population. This study is registered at ClinicalTrials.gov, NCT02770508.
Results: Between November 2015 to October 31, 2020, 336 participants were randomly assigned either to the triple therapy arm (165) or the dual therapy arm (171). After 48 weeks, 153 patients in the triple therapy group (93%) and 155 patients in the double therapy group (91%) achieved virological suppression (difference -2·1%, 95%CI -7·0 to 2·9). Drug-related adverse events were more common in the triple therapy group (p=0·04). Two toxicity-related events led to discontinuation in each group.
Interpretation: Co -formulated darunavir/ ritonavir plus lamivudine has shown non-inferiority and a safer toxicity profile compared to a standard-of-care triple regimen including tenofovir in treatment-naïve patients.
期刊介绍:
The International Journal of Antimicrobial Agents is a peer-reviewed publication offering comprehensive and current reference information on the physical, pharmacological, in vitro, and clinical properties of individual antimicrobial agents, covering antiviral, antiparasitic, antibacterial, and antifungal agents. The journal not only communicates new trends and developments through authoritative review articles but also addresses the critical issue of antimicrobial resistance, both in hospital and community settings. Published content includes solicited reviews by leading experts and high-quality original research papers in the specified fields.