No abstract

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.

The HIV lymphocyte reservoir is dynamic. Its diversity results mainly from successive archiving of circulating plasma viruses during the course of HIV infection. Archiving of resistant virus must be taken into account in therapeutic decisions.

Our findings suggest that a significant proportion of replication-competent HIV-infected CD4 T cells in these patients are memory cells directed against HIV determinants. This may provide a rationale for the therapeutic use of recombinant HIV antigens to reduce the pool of HIV-reservoir cells.