INHIBITION OF THE PROTEASE OF HUMAN-IMMUNODEFICIENCY-VIRUS BLOCKS REPLICATION AND INFECTIVITY OF THE VIRUS IN CHRONICALLY INFECTED MACROPHAGES

Because of the importance of monocytes/macrophages (M/M) as an in vivo reservoir of human immunodeficiency virus (HIV), a study was done to investigate whether viral replication in chronically infected macropha ges (HIV M/M) could be inhibited by various drugs, including U-75875, an inhibitor of HIV protease. HIV replication in M/M and in chronicall y infected T cells was dramatically decreased by U-75875, while other drugs, including zidovudine, interferon-alpha, and an antisense oligod eoxynucleotide against the rev gene, were effective antiviral agents o nly in de novo-infected cells. Virus titer in HIV M/M was reduced appr oximately 10(5)-fold by nontoxic concentrations of U-75875, while no e ffect on HIV DNA or virus antigen expression on cell membrane was achi eved in M/M infected either chronically or de novo. Thus, U-75875 esse ntially worked against late stages of viral replication. These data su pport the use of protease inhibitors, alone or in combination, in the therapy of HIV-infected patients.