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

• Published in: Viruses Vol. 9; no. 10; p. 277
• Main Authors: Borrajo, Ana, Ranazzi, Alessandro, Pollicita, Michela, Bruno, Rosalinda, Modesti, Andrea, Alteri, Claudia, Perno, Carlo Federico, Svicher, Valentina, Aquaro, Stefano
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28-09-2017; MDPI
• Subjects: Amprenavir; Antiviral drugs; Carbamates - pharmacology; Cells, Cultured; HIV; HIV Protease Inhibitors - pharmacology; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus; Humans; Infectivity; Intracellular; Macrophages; Macrophages - virology; Monocytes; Monocytes - virology; monocytes/macrophages; Protease inhibitors; Proteinase inhibitors; Sulfonamides - pharmacology; Virions; Virus Replication - drug effects; protease inhibitors; amprenavir; Human immunodeficiency virus; monocytes/macrophages
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v9100277

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.