During
highly active antiretroviral therapy (
HAART), HIV-1 can still persist in circulating, resting CD4+ T lymphocytes, lymph node mononuclear cells, and seminal cells of patients despite sustained suppression of plasma
viremia to undetectable levels. Sanctuary sites where antiretroviral drug penetration is not optimal may allow local HIV-1
infection of cells within and passing through these tissues. Factors such as imperfect drug adherence due 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 with
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 or more. Replication-competent virus could be recovered from the majority of monocyte populations by co-culture with CD8-depleted, PHA-activated, peripheral blood mononuclear cells. Sequencing of the
reverse transcriptase and
protease genes of the recovered viruses did not reveal resistance to both
reverse transcriptase and
protease inhibitors. Continued new
infection of this transitory, circulating population of cells even during prolonged, effective
HAART most likely reflects ongoing, low-level HIV-1 replication within cellular reservoirs and sanctuary sites in the body.