Relative potency of protease inhibitors in monocytes/macrophages acutely and chronically infected with human immunodeficiency virus

Carlo Federico Perno, Fonda M. Newcomb, David A. Davis, Stefano Aquaro, Rachel W. Humphrey, Raffaele Caliò, Robert Yarchoan

Research output: Contribution to journalArticlepeer-review

Abstract

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, KNI272, and ritonavir inhibited the replication of HIV-1 in vitro, with EC550s of ~ 0.5-3.3 μM. However, only partial inhibition was achievable, even at the highest concentrations tested. Also, the activity of these drugs in chronically infected M/M was ~7- to 26-fold lower than in acutely infected M/M and ~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.

Original languageEnglish
Pages (from-to)413-422
Number of pages10
JournalJournal of Infectious Diseases
Volume178
Issue number2
Publication statusPublished - 1998

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

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