Imperial College London
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ProfessorDeborahAshby

Faculty of Medicine, School of Public Health

Dean of the Faculty of Medicine
 
 
 
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Contact

 

+44 (0)20 7594 8704deborah.ashby Website

 
 
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Location

 

2.15Faculty BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{quinn:2017:10.1038/s41598-017-09230-0,
author = {quinn, K and Traboni, C and Dily, Penchala S and bouliotis, G and doyle, N and libri, V and Khoo, S and ashby, D and weber, J and Nicosia, A and Cortese, R and Pessi, A and Winston, A},
doi = {10.1038/s41598-017-09230-0},
journal = {Scientific Reports},
title = {A first-in-human study of the novel HIV-fusion inhibitor C34-PEG4-Chol.},
url = {http://dx.doi.org/10.1038/s41598-017-09230-0},
volume = {7},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Abstract:Long-acting injectable antiretroviral (LA-ARV) drugs with low toxicity profiles and propensity for drug-drug interactions are a goal for future ARV regimens. C34-PEG4-Chol is a novel cholesterol tagged LA HIV-fusion-inhibitor (FI). We assessed pre-clinical toxicology and first-in-human administration of C34-PEG4-Chol. Pre-clinical toxicology was conducted in 2 species. HIV-positive men were randomised to a single subcutaneous dose of C34-PEG4-Chol at incrementing doses or placebo. Detailed clinical (including injection site reaction (ISR) grading), plasma pharmacokinetic (time-to-minimum-effective-concentration (MEC, 25ng/mL) and pharmacodynamic (plasma HIV RNA) parameters were assessed. In both mice and dogs, no-observed-adverse effect level (NOAEL) was observed at a 12 mg/kg/dose after two weeks. Of 5 men enrolled, 3 received active drug (10mg, 10mg and 20mg). In 2 individuals grade 3 ISR occurred and the study was halted. Both ISR emerged within 12 hours of active drug dosing. No systemic toxicities were observed. The time-to-MEC was > 72 and >96 hours after 10 and 20 mg dose, respectively, and mean change in HIV RNA was -0.9 log10 copies/mL. These human pharmacodynamic and pharmacokinetic data, although limited to 3 subjects, of C34-PEG-4-Chol suggest continuing evaluation of this agent as a LA-ARV. However, alternative administration routes must be explored.
AU  - quinn,K
AU  - Traboni,C
AU  - Dily,Penchala S
AU  - bouliotis,G
AU  - doyle,N
AU  - libri,V
AU  - Khoo,S
AU  - ashby,D
AU  - weber,J
AU  - Nicosia,A
AU  - Cortese,R
AU  - Pessi,A
AU  - Winston,A
DO  - 10.1038/s41598-017-09230-0
PY  - 2017///
SN  - 2045-2322
TI  - A first-in-human study of the novel HIV-fusion inhibitor C34-PEG4-Chol.
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-017-09230-0
UR  - http://hdl.handle.net/10044/1/50145
VL  - 7
ER  -
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