title: Potent antiviral activity of amprenavir in primary macrophages infected by human immunodeficiency virus.
abstract: Objective of the present study was then to assess the antiviral activity of the protease inhibitor amprenavir in macrophages (M/M), and to compare it with its efficacy in peripheral blood lymphocytes (PBL). M/M were obtained from blood of sero-negative healthy donors and infected with M-tropic HIV-1 strain (HIV-1(Ba-L)). The stabilized infection was assessed by monitoring the HIV-1 p24 gag antigen production in the supernatants of M/M cultures. In the setting of acute infection (treatment before HIV-1 challenge), amprenavir showed substantial activity both in M/M and PBL at similar concentrations (EC(50): 0.011 and 0.031 microM, respectively); complete inhibition of HIV-1 replication was achieved in both cell types at concentration of about 2 microM. In the setting of chronical infection (i.e. antiviral treatment several days after established infection), an antiviral effect of amprenavir was achieved in M/M, but at concentrations higher than those active in acutely infected M/M (EC(50): 0.72 microM, EC(90): 18.2 microM). The antiviral effect in chronically infected M/M was sustained for at least 2 weeks of continuous treatment. These findings suggest that amprenavir (at relatively high concentrations) has a clinically relevant antiviral effect in persistently infected reservoirs of HIV.
authors.affiliation: Department of Experimental Medicine and Biochemical Sciences, University of Rome Tor Vergata, Via Montpellie 1, Rome 00133, Italy. aquaro@uniroma2.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Aquaro
authors.forename: Tania
authors.initials: T
authors.lastname: Guenci
authors.forename: Fabiola
authors.initials: F
authors.lastname: Di Santo
authors.forename: Mauro
authors.initials: M
authors.lastname: Francesconi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Caliò
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
mesh_terms: D002219:Carbamates; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D013449:Sulfonamides / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir