Akil Jackson, Laura Else, Christopher Higgs, Zeenat Karolia, Saye Khoo, David Back, Emma Devitt, Anton Pozniak, Marta Boffito
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Secondary endpoints included rilpivirine/darunavir/ritonavir pharmacokinetics, HIV-RNA decay, and changes in ECG QT interval.</p><p><strong>Results: </strong>Thirty-six individuals were enrolled, 18 with a baseline viral load < 100,000 copies/mL (group A) and 18 with a baseline viral load > 100,000 copies/mL (group B). All but 1 (HIV-RNA = 63 copies/mL) subjects achieved viral load < 50 copies/mL by week 36, and all at week 48. Median (range) HIV-RNA reduction (Log10 copies/mL) was 1.3 (0.6-1.9) over the first week, with no differences between groups A and B. Geometric mean and 95%CI rilpivirine C<sub>max</sub>, C<sub>trough</sub>, AUC were 183 (165-239), 114 (104-109) ng/mL, 2966 (2704-3820) ng h/mL. No QTcF interval changes were recorded.</p><p><strong>Conclusions: </strong>rilpivirine/darunavir/ritonavir could be efficacious, with limited short-term toxicity in ARV-naïve patients. Although rilpivirine was co-administered with ritonavir, its exposure was within ranges measured during phase III trials.</p>","PeriodicalId":13216,"journal":{"name":"HIV Clinical Trials","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2018-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/15284336.2017.1408928","citationCount":"4","resultStr":"{\"title\":\"Pharmacokinetics and pharmacodynamics of the nucleoside sparing dual regimen containing rilpivirine plus darunavir/ritonavir in treatment-naïve HIV-1-infected individuals.\",\"authors\":\"Akil Jackson, Laura Else, Christopher Higgs, Zeenat Karolia, Saye Khoo, David Back, Emma Devitt, Anton Pozniak, Marta Boffito\",\"doi\":\"10.1080/15284336.2017.1408928\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>We aimed at investigating the antiviral activity and the pharmacokinetics of the dual antiretroviral (ARV) combination of rilpivirine plus darunavir/ritonavir 25/800/100 mg once-daily in naïve HIV-1-infected individuals (NHII) with different baseline viral loads.</p><p><strong>Settings: </strong>Pharmacokinetic/pharmacodynamics study in ARV-naïve HIV-infected individuals.</p><p><strong>Methods: </strong>The primary endpoint was the number of NHII with HIV-RNA < 40 copies/mL at week 48. Secondary endpoints included rilpivirine/darunavir/ritonavir pharmacokinetics, HIV-RNA decay, and changes in ECG QT interval.</p><p><strong>Results: </strong>Thirty-six individuals were enrolled, 18 with a baseline viral load < 100,000 copies/mL (group A) and 18 with a baseline viral load > 100,000 copies/mL (group B). All but 1 (HIV-RNA = 63 copies/mL) subjects achieved viral load < 50 copies/mL by week 36, and all at week 48. Median (range) HIV-RNA reduction (Log10 copies/mL) was 1.3 (0.6-1.9) over the first week, with no differences between groups A and B. Geometric mean and 95%CI rilpivirine C<sub>max</sub>, C<sub>trough</sub>, AUC were 183 (165-239), 114 (104-109) ng/mL, 2966 (2704-3820) ng h/mL. No QTcF interval changes were recorded.</p><p><strong>Conclusions: </strong>rilpivirine/darunavir/ritonavir could be efficacious, with limited short-term toxicity in ARV-naïve patients. Although rilpivirine was co-administered with ritonavir, its exposure was within ranges measured during phase III trials.</p>\",\"PeriodicalId\":13216,\"journal\":{\"name\":\"HIV Clinical Trials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2018-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1080/15284336.2017.1408928\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"HIV Clinical Trials\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/15284336.2017.1408928\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2017/11/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"HIV Clinical Trials","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/15284336.2017.1408928","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2017/11/30 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 4
摘要
背景:我们旨在研究利匹韦林加达那韦/利托那韦25/800/100 mg每日一次的双重抗逆转录病毒(ARV)联合治疗在naïve hiv -1感染个体(NHII)中具有不同基线病毒载量的抗病毒活性和药代动力学。背景:ARV-naïve hiv感染者的药代动力学/药效学研究。结果:纳入36例患者,18例基线病毒载量为100,000拷贝/mL (B组)。除1例(HIV-RNA = 63拷贝/mL)外,所有受试者均达到病毒载量最大值,Ctrough, AUC分别为183 (165-239),114 (104-109)ng/mL, 2966 (2704-3820) ng h/mL。未见QTcF时间间隔变化。结论:利匹韦林/达那韦/利托那韦对ARV-naïve患者有效,短期毒性有限。虽然利匹韦林与利托那韦同时给药,但其暴露量在III期试验期间测量的范围内。
Pharmacokinetics and pharmacodynamics of the nucleoside sparing dual regimen containing rilpivirine plus darunavir/ritonavir in treatment-naïve HIV-1-infected individuals.
Background: We aimed at investigating the antiviral activity and the pharmacokinetics of the dual antiretroviral (ARV) combination of rilpivirine plus darunavir/ritonavir 25/800/100 mg once-daily in naïve HIV-1-infected individuals (NHII) with different baseline viral loads.
Settings: Pharmacokinetic/pharmacodynamics study in ARV-naïve HIV-infected individuals.
Methods: The primary endpoint was the number of NHII with HIV-RNA < 40 copies/mL at week 48. Secondary endpoints included rilpivirine/darunavir/ritonavir pharmacokinetics, HIV-RNA decay, and changes in ECG QT interval.
Results: Thirty-six individuals were enrolled, 18 with a baseline viral load < 100,000 copies/mL (group A) and 18 with a baseline viral load > 100,000 copies/mL (group B). All but 1 (HIV-RNA = 63 copies/mL) subjects achieved viral load < 50 copies/mL by week 36, and all at week 48. Median (range) HIV-RNA reduction (Log10 copies/mL) was 1.3 (0.6-1.9) over the first week, with no differences between groups A and B. Geometric mean and 95%CI rilpivirine Cmax, Ctrough, AUC were 183 (165-239), 114 (104-109) ng/mL, 2966 (2704-3820) ng h/mL. No QTcF interval changes were recorded.
Conclusions: rilpivirine/darunavir/ritonavir could be efficacious, with limited short-term toxicity in ARV-naïve patients. Although rilpivirine was co-administered with ritonavir, its exposure was within ranges measured during phase III trials.
期刊介绍:
HIV Clinical Trials is devoted exclusively to presenting information on the latest developments in HIV/AIDS clinical research. This journal enables readers to obtain the most up-to-date, innovative research from around the world.