EFFECT OF 3'-AZIDO-3'-DEOXYTHYMIDINE AND 2',3'-DIDEOXYINOSINE ON ESTABLISHMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION IN CULTURED CD8(+) LYMPHOCYTES

Several groups have shown that peripheral CD8(+) lymphocytes can be infected with human immunodeficiency virus type 1 (HIV-1), resulting in noncytopathic infection and persistent production of viral particles. We studied the ability of 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI) to inhibit the establishment of HIV-1 infection in CD8(+) cells that were derived from cultures of peripheral blood lymphocytes exposed to both virus and drug. In situ infection of CD8(+) cells was demonstrated by double dow cytometry analysis by using both anti-glycoprotein 120 (anti-gp120) and anti-CD8 monoclonal antibodies. At higher concentrations of drug (e.g., 0.4 mu M AZT), the production of viral particles was inhibited for over 2 months, as assessed by p24 antigen levels in the culture medium. We also performed a time course experiment to determine whether HTV-1 infection of CD8(+) cells would be affected by treatment of peripheral blood lymphocytes with AZT or ddI for different intervals following exposure to virus. Quantitative PCR revealed that 0.4 mu M AZT, added as late as 24 h after infection, interfered with the formation of proviral DNA in CD8(+) cells. Both HIV-1 load and the production of progeny virions by CD8(+) cells, as monitored by reverse transcriptase activity in culture fluids, were inhibited by both AZT and ddI in a dose-dependent manner.