HIV-1 can be recovered from a variety of cells including peripheral blood monocytes of patients receiving highly active antiretroviral therapy: a further obstacle to eradication

During highly active antiretroviral therapy (HAART), HIV-1 can still persis t in circulating, resting CD4(+) T lymphocytes, lymph node mononuclear cell s, and seminal cells of patients despite sustained suppression of plasma vi remia to undetectable levels. Sanctuary sites where antiretroviral drug pen etration is not optimal may allow local HIV-1 infection of cells within and passing through these tissues. Factors such as imperfect drug adherence du e to complicated drug regimens may also result in tissue compartments with suboptimal drug concentrations allowing viral replication. We have examined blood monocytes from HIV-1-infected subjects being effectively treated wit h HAART to determine virus carriage in these cells. Monocytes were purified from peripheral blood of patients with plasma HIV-1 RNA below 50 copies/mL and who had maintained levels of plasma RNA below detection for 3 months o r more. Replication-competent virus could be recovered from the majority of monocyte populations by co-culture with CD8-depleted, PHA-activated, perip heral blood mononuclear cells. Sequencing of the reverse transcriptase and protease genes of the recovered viruses did not reveal resistance to both r everse transcriptase and protease inhibitors. Continued new infection of th is transitory, circulating population of cells even during prolonged, effec tive HAART most likely reflects ongoing, low-level HIV-1 replication within cellular reservoirs and sanctuary sites in the body.