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Viruses 2017, 9(10), 277; doi:10.3390/v9100277

Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages

1
Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Roma, Italy
2
Clinical Virology Group, Institute of Biomedical Research of A Coruña (INIBIC)-University Hospital of A Coruña (CHUAC), Sergas, University of A Coruña (UDC), 15001 A Coruña, Spain
3
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
4
Department of Clinical Sciences and Translational Medicine University of Rome Tor Vergata, 00133 Roma, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 24 July 2017 / Revised: 23 September 2017 / Accepted: 26 September 2017 / Published: 28 September 2017
(This article belongs to the Section Antivirals & Vaccines)
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Abstract

A paucity of information is available on the activity of protease inhibitors (PI) in chronically-infected monocyte-derived macrophages (MDM) and on the kinetics of viral-rebound after PI removal in vitro. To fill this gap, the activity of different concentrations of amprenavir (AMP) was evaluated in chronically-infected MDM by measuring p24-production every day up to 12 days after drug administration and up to seven days after drug removal. Clinically-relevant concentrations of AMP (4 and 20 μM) drastically decreased p24 amount released from chronically-infected MDM from Day 2 up to Day 12 after drug administration. The kinetics of viral-rebound after AMP-removal (4 and 20 μM) showed that, despite an initial increase, p24-production over time never reached the level observed for untreated-MDM, suggesting a persistent intracellular drug activity. In line with this, after AMP-removal, human immunodeficiency virus 1 (HIV-1) infectivity and intracellular the p24/p55 ratio (reflecting virion-maturation) were remarkably lower than observed for untreated MDM. Overall, AMP shows high efficacy in blocking HIV-1 replication in chronically-infected MDM, persisting even after drug-removal. This highlights the role of protease inhibitors in preventing the establishment of this important HIV-1 reservoir, thus reducing viral-dissemination in different anatomical compartments. View Full-Text
Keywords: amprenavir; Human immunodeficiency virus; monocytes/macrophages; protease inhibitors amprenavir; Human immunodeficiency virus; monocytes/macrophages; protease inhibitors
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Borrajo, A.; Ranazzi, A.; Pollicita, M.; Bruno, R.; Modesti, A.; Alteri, C.; Perno, C.F.; Svicher, V.; Aquaro, S. Effects of Amprenavir on HIV-1 Maturation, Production and Infectivity Following Drug Withdrawal in Chronically-Infected Monocytes/Macrophages. Viruses 2017, 9, 277.

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