Relative potency of protease inhibitors in monocytes/macrophages acutely and chronically infected with human immunodeficiency virus.
The activity of three human immunodeficiency virus (HIV) protease inhibitors was investigated in human primary monocytes/macrophages (M/M) chronically infected by HIV-1. Saquinavir, KNI-272, and ritonavir inhibited the replication of HIV-1 in vitro, with EC50s of approximately 0.5-3.3 microM. However, only partial inhibition was achievable, even at the highest concentrations tested. Also, the activity of these drugs in chronically infected M/M was approximately 7- to 26-fold lower than in acutely infected M/M and approximately 2- to 10-fold lower than in chronically infected H9 lymphocytes. When protease inhibitors were removed from cultures of chronically infected M/M, production of virus rapidly returned to the levels found in untreated M/M. Therefore, relatively high concentrations of protease inhibitors are required to suppress HIV-1 production in chronically infected macrophages, and such cells may be a vulnerable point for the escape of virus in patients taking these drugs.
Perno
C F
CF
HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Newcomb
F M
FM
Davis
D A
DA
Aquaro
S
S
Humphrey
R W
RW
Caliò
R
R
Yarchoan
R
R
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000032:analysis; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology*; D009842:Oligopeptides / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D019438:Ritonavir / Q000494:pharmacology*; D019258:Saquinavir / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology
D019380:Anti-HIV Agents; D016655:HIV Core Protein p24; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019258:Saquinavir; C077822:kynostatin 272; D019438:Ritonavir