Zidovudine, lamivudine, and abacavir have different effects on resting cells infected with human immunodeficiency virus in vitro.
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).
Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, USA.
Jesús
J
Saavedra-Lozano
Cynthia C
CC
McCoig
Yanying
Y
Cao
Ellen S
ES
Vitetta
Octavio
O
Ramilo
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D015224:Dideoxynucleosides / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology; D019259:Lamivudine / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D016655:HIV Core Protein p24; D000922:Immunotoxins; D019259:Lamivudine; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D000099227:Abacavir