Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy

Background and Methods Although potent antiretroviral therapy can control i nfection with human immunodeficiency virus type 1 (HIV-1), a long-lived res ervoir of infectious virus persists in CD4+ T cells. We investigated this v iral reservoir by measuring the levels of cell-associated viral DNA and mes senger RNA (mRNA) that are essential for HIV-1 replication. Approximately e very 6 months, we obtained samples of peripheral-blood mononuclear cells fr om five men with long-standing HIV-1 infection who had had undetectable lev els of plasma HIV-1 RNA for 20 months or more during treatment with potent antiretroviral drugs. Results Before treatment, plasma levels of HIV-1 RNA correlated with the le vels of cell-associated unintegrated HIV-1 DNA and unspliced viral mRNA. Af ter treatment, plasma levels of HIV-1 RNA fell by more than 2.7 log to unde tectable levels. The decrease in cell-associated integrated and unintegrate d HIV-1 DNA and mRNA occurred in two phases. The first phase occurred durin g the initial 500 days of treatment and was characterized by substantial de creases in the levels of DNA and mRNA, but not to undetectable levels. The concentrations of cell-associated unintegrated viral DNA, integrated provir al DNA, and unspliced viral mRNA decreased by 1.25 to 1.46 log. The second phase occurred during the subsequent 300 days or more of treatment and was characterized by a plateau in the levels of HIV-1 DNA and unspliced mRNA. A fter an initial rapid decline, the ratio of unspliced to multiply spliced v iral mRNA (a measure of active viral transcription) stabilized and remained greater than zero at each measurement. Conclusions Despite treatment with potent antiretroviral drugs and the supp ression of plasma HIV-1 RNA to undetectable levels for 20 months or more, H IV-1 transcription persists in peripheral-blood mononuclear cells. Unless t he quasi-steady state levels of HIV DNA and mRNA eventually disappear with longer periods of therapy, these findings suggest that HIV-1 infection cann ot be eradicated with current treatments. (N Engl J Med 1999;340:1614-22.) (C) 1999, Massachusetts Medical Society.