Ultra-long-acting removable drug delivery system for HIV treatment and prevention

被引：80

作者：

Kovarova, Martina ^{[1
]}

Benhabbour, S. Rahima ^{[2
]}

Massud, Ivana ^{[3
]}

Spagnuolo, Rae Ann ^{[1
]}

Skinner, Brianna ^{[4
]}

Baker, Caroline E. ^{[1
]}

Sykes, Craig ^{[5
]}

Mollan, Katie R. ^{[6
]}

Kashuba, Angela D. M. ^{[5
]}

Garcia-Lerma, J. Gerardo ^{[3
]}

Mumper, Russell J. ^{[2
]}

Garcia, J. Victor ^{[1
]}

机构：

[1] Univ N Carolina, Sch Med, Dept Med, Div Infect Dis,Ctr AIDS Res, 120 Mason Farm Rd CB 7042, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, UNC Eshelman Sch Pharm, Div Mol Pharmaceut, 125 Mason Farm Rd 4205, Chapel Hill, NC 27599 USA

[3] Ctr Dis Control & Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Div HIV AIDS Prevent, Branch Lab, 1600 Clifton Rd,MS G45, Atlanta, GA 30329 USA

[4] Ctr Dis Control & Prevent, Comparat Med Branch, Div Sci Resources, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30329 USA

[5] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, UNC Eshelman Sch Pharm, 120 Mason Farm Rd CB 7361, Chapel Hill, NC 27599 USA

[6] Univ N Carolina, Ctr AIDS Res, 3126 McGavran Greenberg Hall, Chapel Hill, NC 27599 USA

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

HUMANIZED BLT MICE; FEMALE REPRODUCTIVE-TRACT; PREEXPOSURE PROPHYLAXIS; ANTIRETROVIRAL PROPHYLAXIS; AFRICAN WOMEN; INFECTION; DOLUTEGRAVIR; TENOFOVIR; TRANSMISSION; FORMULATION;

D O I：

10.1038/s41467-018-06490-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Non-adherence to medication is an important health care problem, especially in the treatment of chronic conditions. Injectable long-acting (LA) formulations of antiretrovirals (ARVs) represent a viable alternative to improve adherence to HIV/AIDS treatment and prevention. However, the LA-ARV formulations currently in clinical trials cannot be removed after administration even if adverse events occur. Here we show an ultra-LA removable system that delivers drug for up to 9 months and can be safely removed to stop drug delivery. We use two pre-clinical models for HIV transmission and treatment, non-human primates (NHP) and humanized BLT (bone marrow/liver/thymus) mice and show a single dose of subcutaneously administered ultra-LA dolutegravir effectively delivers the drug in both models and show suppression of viremia and protection from multiple high-dose vaginal HIV challenges in BLT mice. This approach represents a potentially effective strategy for the ultra-LA drug delivery with multiple possible therapeutic applications.

引用

页数：11

共 45 条

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