Detection of Infectious HIV in Circulating Monocytes From Patients on Prolonged Highly Active Antiretroviral Therapy

Abstract

Summary:The existence of a reservoir of resting CD4+ T cells harboring latent replication-competent HIV has been demonstrated in patients on prolonged highly active antiretroviral therapy (HAART). Latently infected tissue macrophages may constitute a second HIV reservoir. The pool of these cells may be maintained by incoming infected monocytes from blood and/or by in situ viral replication. In this study, the presence of infectious HIV was investigated in highly purified monocytes from 5 patients receiving HAART with undetectable plasma viral load for up to 16 months. HIV was detected in freshly isolated monocytes and recovered following Staphylococcus aureus Cowan strain 1 (SAC) or lipopolysaccharide (LPS) activation. No new drug resistance-associated mutation was found in monocyte-associated HIV. These results demonstrate the long-term persistence of infectious virus in cells of the monocyte-macrophage lineage in patients receiving HAART. These cells are capable of releasing infectious virus under appropriate stimulations. Address correspondence and reprint requests to Y. Taoufik, Laboratoire Virus, Neurone et Immunité (CR INSERM 96012), Faculté de Médecine Paris Sud, Université Paris Sud, 63 rue Gabriel Péri, 94276, Le Kremlin-Bicêtre, France; email: [email protected] O. Lambotte and Y. Taoufik contributed equally to this work. Manuscript received May 13, 1999; accepted November 26, 1999. © 2000 Lippincott Williams & Wilkins, Inc.