Eradication of human immunodeficiency virus type 1-infected cells by a combination of antimetabolic cytotoxic chemotherapy and antiviral chemotherapy in vitro: a pilot study.
Although highly active antiretroviral therapy against human immunodeficiency virus (HIV) type 1 reduces the mortality of persons with acquired immunodeficiency syndrome, it does not eliminate HIV reservoirs. In this study, which used a 6-thioguanine (6-TG) resistant clone (4C6) of the MT-2 cell line as a model, the combination of 6-TG with both reverse-transcriptase (RT) inhibitor and protease inhibitor or 6-TG with a protease inhibitor alone completely eradicated HIV-1-carrying cells from the culture and protected uninfected 4C6 cells from HIV-1 infection. The combination of 6-TG and a RT inhibitor, azidothymidine, provided partial protection. Protection was extended to human peripheral blood mononuclear cells. These results suggest that adding a cytotoxic drug in combination antiviral chemotherapy may reduce the establishment of virus reservoirs and prevent virus spread. The clinical value of this and similar strategies should be further evaluated in HIV-infected patients.
Laboratory of Antiviral Drug Mechanisms, Science Applications International Corporation-Frederick, National Cancer Institute, Frederick, Maryland 21702, USA. yangq@dtpax2.ncifcrf.gov
Quan-en
QE
Yang
Kun-gui
KG
Li
Judy A
JA
Mikovits
D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D010865:Pilot Projects; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013866:Thioguanine / Q000494:pharmacology*
D016655:HIV Core Protein p24; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D013866:Thioguanine