Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia.

Background: In many patients with human immunodeficiency virus (HIV) infect ion, therapy with potent antiretroviral drugs does not result in complete s uppression of HIV replication. The effect of cessation of therapy in these patients is unknown. Methods: Sixteen patients who had a plasma HIV RNA level of more than 2500 copies per milliliter during combination antiretroviral-drug therapy were r andomly assigned, in a 2:1 ratio, to discontinue or continue therapy. Plasm a HIV RNA levels, CD4 cell counts, and drug susceptibility were measured we ekly. Viral replicative capacity was measured at base line and at week 12. Results: Discontinuation of therapy for 12 weeks was associated with a medi an decrease in the CD4 cell count of 128 cells per cubic millimeter and an increase in the plasma HIV RNA level of 0.84 log copies per milliliter. Vir us from all patients with detectable resistance at entry became susceptible to HIV-protease inhibitors within 16 weeks after the discontinuation of th erapy. Drug susceptibility began to increase a median of six weeks after th e discontinuation of therapy and was temporally associated with increases i n plasma HIV RNA levels and decreases in CD4 cell counts. Viral replicative capacity, measured by means of a recombinant-virus assay, was low at entry into the study and increased after therapy was discontinued. Despite the l oss of detectable resistance in plasma, resistant virus was cultured from p eripheral-blood mononuclear cells in five of nine patients who could be eva luated. Plasma HIV RNA levels, CD4 cell counts, and drug susceptibility rem ained stable in the patients who continued therapy. Conclusions: Despite the presence of reduced drug susceptibility, antiretro viral-drug therapy can provide immunologic and virologic benefit. This bene fit reflects continued antiviral-drug activity and the maintenance of a vir al population with a reduced replicative capacity. (N Engl J Med 2001;344:4 72-80.) Copyright (C) 2001 Massachusetts Medical Society.