{"title":"艾滋病、肝炎和其他抗病毒药物临床药理学国际研讨会摘要。","authors":"","doi":"10.1111/bcp.16304","DOIUrl":null,"url":null,"abstract":"<p><b>25</b></p><p><b>Safety, pharmacokinetics and antiviral activity of ainuovirine as 10-day monotherapy in treatment-naïve adults with HIV-1</b></p><p>Su Bin<sup>1</sup>, Wu Hao<sup>1</sup>, Wei Xia<sup>1</sup>, Zhang Li<sup>2</sup>, Yun Xinming<sup>2</sup> and Qin Hong<sup>2</sup></p><p><sup>1</sup><i>Beijing Youan Hospital Affiliated to Capital Medical University;</i> <sup>2</sup><i>Jiangsu Aidea Pharmaceutical Co., Ltd</i></p><p><b>Background:</b> Ainuovirine (ANV) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of HIV-1 infection. This study aimed to evaluate the safety, pharmacokinetics and antiviral activity of short-term ANV monotherapy in antiretroviral treatment-naive adults with HIV-1.</p><p><b>Methods:</b> A single-centre, open-label, dose-ranging study was conducted among 28 treatment-naive adults with HIV-1. Participants received ainuovirine monotherapy, at the dosage of 75, 150 or 300 mg, once daily, for 10 days.</p><p><b>Results:</b> Baseline characteristics were similar across dose cohorts (75 mg, <i>n</i> = 8; 150 mg, <i>n</i> = 10; 300 mg, <i>n</i> = 10). Across all dose cohorts, all adverse events were rated as mild to moderate in severity. No serious adverse event was reported. ANV was readily absorbed, with the maximum concentration achieved at a median time of approximately 2–3 h after dosing. The ANV exposure (AUC and C<sub>max</sub>) increased slightly greater than the dose proportionality after single dose (day 1). Plasma ANV concentration reached the steady state at day 10 of dosing. Saturated C<sub>max,ss</sub>, AUC<sub>max,ss</sub>, and C<sub>min,ss</sub> were observed at 150 and 300 mg on day 10 after repeated dosing. The inhibitory quotient (IQ) was 69.6-fold (150 mg, C<sub>min,ss</sub> = 153.0 ng/mL) for wild type (EC50 = 2.2 ng/mL), 10.0-fold for K103N mutant (EC50 = 15.3 ng/mL) and 6.9-fold for Y181C mutant (EC50 = 22.1 ng/mL), respectively. Mean changes in HIV RNA from baseline (log10 copies/mL [90%CI]) were −1.73 [−1.90, −1.57], −1.72 [−1.87, −1.57] and −1.66 [−1.80, −1.51], respectively, on day 11.</p><p><b>Conclusion:</b> ANV demonstrated favourable safety and pharmacokinetics, and potent antiviral activity in treatment-naive adults with HIV-1. An once-daily dosing regimen of 150 mg was recommended for subsequent confirmatory efficacy trial.</p><p><b>Keywords:</b> ainuovirine, anti-HIV treatment, viral kinetics</p>","PeriodicalId":3,"journal":{"name":"ACS Applied Electronic Materials","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16304","citationCount":"0","resultStr":"{\"title\":\"Safety, pharmacokinetics and antiviral activity of ainuovirine as 10-day monotherapy in treatment-naïve adults with HIV-1\",\"authors\":\"\",\"doi\":\"10.1111/bcp.16304\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><b>25</b></p><p><b>Safety, pharmacokinetics and antiviral activity of ainuovirine as 10-day monotherapy in treatment-naïve adults with HIV-1</b></p><p>Su Bin<sup>1</sup>, Wu Hao<sup>1</sup>, Wei Xia<sup>1</sup>, Zhang Li<sup>2</sup>, Yun Xinming<sup>2</sup> and Qin Hong<sup>2</sup></p><p><sup>1</sup><i>Beijing Youan Hospital Affiliated to Capital Medical University;</i> <sup>2</sup><i>Jiangsu Aidea Pharmaceutical Co., Ltd</i></p><p><b>Background:</b> Ainuovirine (ANV) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of HIV-1 infection. This study aimed to evaluate the safety, pharmacokinetics and antiviral activity of short-term ANV monotherapy in antiretroviral treatment-naive adults with HIV-1.</p><p><b>Methods:</b> A single-centre, open-label, dose-ranging study was conducted among 28 treatment-naive adults with HIV-1. Participants received ainuovirine monotherapy, at the dosage of 75, 150 or 300 mg, once daily, for 10 days.</p><p><b>Results:</b> Baseline characteristics were similar across dose cohorts (75 mg, <i>n</i> = 8; 150 mg, <i>n</i> = 10; 300 mg, <i>n</i> = 10). Across all dose cohorts, all adverse events were rated as mild to moderate in severity. No serious adverse event was reported. ANV was readily absorbed, with the maximum concentration achieved at a median time of approximately 2–3 h after dosing. The ANV exposure (AUC and C<sub>max</sub>) increased slightly greater than the dose proportionality after single dose (day 1). Plasma ANV concentration reached the steady state at day 10 of dosing. Saturated C<sub>max,ss</sub>, AUC<sub>max,ss</sub>, and C<sub>min,ss</sub> were observed at 150 and 300 mg on day 10 after repeated dosing. The inhibitory quotient (IQ) was 69.6-fold (150 mg, C<sub>min,ss</sub> = 153.0 ng/mL) for wild type (EC50 = 2.2 ng/mL), 10.0-fold for K103N mutant (EC50 = 15.3 ng/mL) and 6.9-fold for Y181C mutant (EC50 = 22.1 ng/mL), respectively. Mean changes in HIV RNA from baseline (log10 copies/mL [90%CI]) were −1.73 [−1.90, −1.57], −1.72 [−1.87, −1.57] and −1.66 [−1.80, −1.51], respectively, on day 11.</p><p><b>Conclusion:</b> ANV demonstrated favourable safety and pharmacokinetics, and potent antiviral activity in treatment-naive adults with HIV-1. An once-daily dosing regimen of 150 mg was recommended for subsequent confirmatory efficacy trial.</p><p><b>Keywords:</b> ainuovirine, anti-HIV treatment, viral kinetics</p>\",\"PeriodicalId\":3,\"journal\":{\"name\":\"ACS Applied Electronic Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-10-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcp.16304\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Electronic Materials\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/bcp.16304\",\"RegionNum\":3,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, ELECTRICAL & ELECTRONIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Electronic Materials","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/bcp.16304","RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, ELECTRICAL & ELECTRONIC","Score":null,"Total":0}
Safety, pharmacokinetics and antiviral activity of ainuovirine as 10-day monotherapy in treatment-naïve adults with HIV-1
25
Safety, pharmacokinetics and antiviral activity of ainuovirine as 10-day monotherapy in treatment-naïve adults with HIV-1
Su Bin1, Wu Hao1, Wei Xia1, Zhang Li2, Yun Xinming2 and Qin Hong2
1Beijing Youan Hospital Affiliated to Capital Medical University;2Jiangsu Aidea Pharmaceutical Co., Ltd
Background: Ainuovirine (ANV) is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) for treatment of HIV-1 infection. This study aimed to evaluate the safety, pharmacokinetics and antiviral activity of short-term ANV monotherapy in antiretroviral treatment-naive adults with HIV-1.
Methods: A single-centre, open-label, dose-ranging study was conducted among 28 treatment-naive adults with HIV-1. Participants received ainuovirine monotherapy, at the dosage of 75, 150 or 300 mg, once daily, for 10 days.
Results: Baseline characteristics were similar across dose cohorts (75 mg, n = 8; 150 mg, n = 10; 300 mg, n = 10). Across all dose cohorts, all adverse events were rated as mild to moderate in severity. No serious adverse event was reported. ANV was readily absorbed, with the maximum concentration achieved at a median time of approximately 2–3 h after dosing. The ANV exposure (AUC and Cmax) increased slightly greater than the dose proportionality after single dose (day 1). Plasma ANV concentration reached the steady state at day 10 of dosing. Saturated Cmax,ss, AUCmax,ss, and Cmin,ss were observed at 150 and 300 mg on day 10 after repeated dosing. The inhibitory quotient (IQ) was 69.6-fold (150 mg, Cmin,ss = 153.0 ng/mL) for wild type (EC50 = 2.2 ng/mL), 10.0-fold for K103N mutant (EC50 = 15.3 ng/mL) and 6.9-fold for Y181C mutant (EC50 = 22.1 ng/mL), respectively. Mean changes in HIV RNA from baseline (log10 copies/mL [90%CI]) were −1.73 [−1.90, −1.57], −1.72 [−1.87, −1.57] and −1.66 [−1.80, −1.51], respectively, on day 11.
Conclusion: ANV demonstrated favourable safety and pharmacokinetics, and potent antiviral activity in treatment-naive adults with HIV-1. An once-daily dosing regimen of 150 mg was recommended for subsequent confirmatory efficacy trial.
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