Geretti, AM

Grp, UoL Nano-ARV Study

Villa, G

University of Liverpool Repository

FOURTH JOINT CONFERENCE OF BHIVA WITH BASHH17-20 APRIL 2018, EDINBURGH INTERNATIONAL CONFERENCE CENTREAbstract Template – BHIVA BASHH Conference 2018Title: .	Antiretrovirals in nanoparticle formulation to improve control of HIV replication and prevent viral escape Please do not add the names of authors or affiliations on this formUse a concise title that indicates the nature of the study.Please capitalise the first letter of the title and use lower case for the rest of the title (with the exception of proper nouns or abbreviations).e.g. Recall of men who have sex with men diagnosed with bacterial sexually transmitted infections for retesting: a feasible and effective strategy?  Please do not use a full stop at the end of the titleAbstract:Your abstract must be pasted into the space to the right and use the Arial font in size 10. Your abstract must not exceed a maximum of 2,500 characters (including spaces and tables).Please follow the general outline Background, Methods, Results and Conclusion where applicable.Please ensure that your abstract is thoroughly proof read for grammatical inaccuracies.	BackgroundART is highly effective in controlling HIV-1 infection, but available agents have limitations, such as variable bioavailability and tissue penetration, short and long-term toxicity, and selection of drug resistance. Nanomedicine creates new opportunities to overcome the shortcomings of conventionally formulated drugs though improved pharmacokinetics and pharmacodynamics. With support from a BHIVA Research Award, this study optimised a cell culture model to study in vitro the antiviral activity of nanoparticle (NP)-formulated relative to standard-formulation (SF) antiretrovirals. MethodsNP-efavirenz (EFV) and NP-lopinavir (LPV) were tested for their ability to inhibit HIV-1 replication and prevent escape through the emergence of drug-resistant variants. NP-EFV and NF-LPV had been generated through integrated materials and pharmacology research at the University of Liverpool. In vitro culture models were optimised to test the antiviral activity of NP-EFV and NP-LPV against laboratory-adapted HIV-1IIIB and patient-derived clinical isolates of HIV-1 subtype B, both grown in cord blood mononuclear cells (CBMC), using reverse transcriptase (RT) activity as a read-out of virus replication. Passage experiments investigated the kinetics and patterns of emerging drug-resistant variants, which were characterised by Sanger sequencing. ResultsIn parallel experiments, NP-EFV effectively suppressed HIV-1 replication in CBMC, with 50% inhibitory concentration (IC50) ranges that were comparable to those of SF-EFV. The IC50 values with SF-EFV vs. NP-EFV were 0.7-1.0 nM vs. 1.0-1.1 nM with HIV-1IIIB, and 1.2-3.1 nM vs. 1.0-3.8 nM with clinical isolates of HIV-1 subtype B. Data were highly reproducible. In passage experiments over 16 weeks, virus escape was slower with NP-EFV relative to SF-EFV. In addition, strains growing at week 16 showed a different resistance profile. With HIV-1IIIB, major emerging mutations in RT were K103N+L100I with SF-EFV and Y188C+L100I with NF-EFV. There were no significant differenced observed in the resistance kinetics and patterns of NP-LPV vs. SF-LPV. ConclusionsAn in vitro culture system was successfully optimised for the reproducible measurement of HIV-1 inhibition and escape in the presence of nanoparticle-formulated antiretrovirals. Further studies are required to validate the use of clinical isolates other than subtype B, and the influence of cell types other than CBMC. 4TH Joint Conference of BHIVA with BASHH EICC · UK  · 17–20 April 2018

Antiretrovirals in nanoparticle formulation to improve control of HIV replication and prevent viral escape

http://livrepository.liverpool.ac.uk/3021507/1/Geretti_BHIVA2018_AwardAbstract.doc

Antiretrovirals in nanoparticle formulation to improve control of HIV replication and prevent viral escape

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