Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy.
Development of an oral once-weekly drug delivery system for HIV antiretroviral therapy.
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DOI：
10.1038/s41467-017-02294-6
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发表时间：
2018-01-09
影响因子：
16.6
通讯作者：
Traverso G
中科院分区：
文献类型：
--
作者：
Kirtane AR;Abouzid O;Minahan D;Bensel T;Hill AL;Selinger C;Bershteyn A;Craig M;Mo SS;Mazdiyasni H;Cleveland C;Rogner J;Lee YL;Booth L;Javid F;Wu SJ;Grant T;Bellinger AM;Nikolic B;Hayward A;Wood L;Eckhoff PA;Nowak MA;Langer R;Traverso G
抗逆转录病毒疗法的疗效因不坚持服药而大打折扣。还没有开发出可以减轻日常坚持负担的长效肠内系统。在这里，我们描述了一种由不同的药物-聚合物基质组成的口服剂型，其在猪中实现了抗逆转录病毒药物度鲁特韦、利匹韦林和卡博特韦的长达一周的全身药物水平。对病毒动力学和患者依从性模式的模拟表明，这种系统将大大减少治疗失败，流行病学模型表明，主动使用这种干预措施可以避免数十万新的艾滋病毒病例。总之，通过一种新型口服剂型每周给予长效抗逆转录病毒药物是一种有希望的干预措施，有助于控制全球艾滋病毒流行。对每日抗逆转录病毒药物的依从性差可显著影响治疗效果，但目前缺乏口服长效抗逆转录病毒药物。在这里，作者开发了一种每周一次的抗HIV药物口服剂型，评估其在猪中的药代动力学，并模拟其对病毒抗性和疾病流行的影响。
The efficacy of antiretroviral therapy is significantly compromised by medication non-adherence. Long-acting enteral systems that can ease the burden of daily adherence have not yet been developed. Here we describe an oral dosage form composed of distinct drug–polymer matrices which achieved week-long systemic drug levels of the antiretrovirals dolutegravir, rilpivirine and cabotegravir in a pig. Simulations of viral dynamics and patient adherence patterns indicate that such systems would significantly reduce therapeutic failures and epidemiological modelling suggests that using such an intervention prophylactically could avert hundreds of thousands of new HIV cases. In sum, weekly administration of long-acting antiretrovirals via a novel oral dosage form is a promising intervention to help control the HIV epidemic worldwide. Poor adherence to daily antiretrovirals can significantly affect treatment efficacy, but oral long-acting antiretrovirals are currently lacking. Here, the authors develop a once-weekly oral dosage form for anti-HIV drugs, assess its pharmacokinetics in pigs, and model its impact on viral resistance and disease epidemics.
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DOI：
10.1097/qai.0000000000000172
发表时间：
2014-07-01
期刊：
Journal of acquired immune deficiency syndromes (1999)
影响因子：
--
作者：
Donnell D;Baeten JM;Bumpus NN;Brantley J;Bangsberg DR;Haberer JE;Mujugira A;Mugo N;Ndase P;Hendrix C;Celum C
通讯作者：
Celum C
影响因子：
3.8
作者：
Bangsberg, DR;Perry, S;Moss, A
通讯作者：
Moss, A
影响因子：
1.7
作者：
Bekker, Linda-Gail;Rebe, Kevin;Eakles, Robyn
通讯作者：
Eakles, Robyn
影响因子：
1.4
作者：
Buscher, A.;Hartman, C.;Giordano, T. P.
通讯作者：
Giordano, T. P.
影响因子：
34.3
作者：
Eaton, Jeffrey W.;Bacaer, Nicolas;Hallett, Timothy B.
通讯作者：
Hallett, Timothy B.