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Antimicrobial Agents and Chemotherapy, August 2004, p. 2825-2830, Vol. 48, No. 8
0066-4804/04/$08.00+0 DOI: 10.1128/AAC.48.8.2825-2830.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Cancer Immunobiology Center,1 Departments of Pediatrics,2 Microbiology, University of Texas Southwestern Medical Center,3 Children's Medical Center, Dallas, Texas4
Received 30 July 2003/ Returned for modification 12 November 2003/ Accepted 25 April 2004
We have previously described an in vitro model for the evaluation of the effects of different immunomodulatory agents and immunotoxins (ITs) on cells latently infected with human immunodeficiency virus (HIV). We demonstrated that latently infected, replication-competent cells can be generated in vitro after eliminating CD25+ cells with an IT. Thus, by selectively killing the productively infected cells with an anti-CD25 IT we can generate a population of latently infected cells. CD25 cells generated in this manner were treated with nucleoside analog reverse transcriptase inhibitors and subsequently activated with phytohemagglutinin in the presence of the drugs. The antiviral activities of zidovudine (ZDV), lamivudine (3TC), and abacavir (ABC) were evaluated by using this model. 3TC and ABC demonstrated significant activity in decreasing HIV production from recently infected resting cells following their activation, whereas the effect of ZDV was more modest. These results suggest that the differences in antiviral activity of nucleoside analogs on resting cells should be considered when designing drug combinations for the treatment of HIV infection. The model presented here offers a convenient alternative for evaluating the mechanism of action of new antiretroviral agents (J. Saavedra, C. Johnson, J. Koester, M. St. Claire, E. Vitteta, O. Ramilo, 37th Intersci. Conf. Antimicrob. Agents Chemother., abstr. I-59, 1997).
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