AZT demonstrates anti-HIV-1 activity in persistently infected cell lines: implications for combination chemotherapy and immunotherapy.
A sensitive and quantitative focal immunoassay has been used to measure the effects of three different therapeutic agents on tissue culture cells infected with human immunodeficiency virus (HIV). The effects of the drugs were studied on both acutely and persistently infected CD4+ cell lines. The three agents, azidothymidine (AZT), interferon-alpha (IFN-alpha), and an anti-HIV envelope antibody coupled to ricin A chain, were tested alone and in combination. AZT was found to have its greatest effect during early stages of the infection, but also had an action on persistently infected T cell lines. The effect of AZT on persistently infected cells was seen within 24 h, increased with extended exposure to the drug, and persisted after its removal. IFN-alpha had variable effects on acutely infected cells but suppressed chronic infection. Combinations of the therapeutic agents were studied. Using a model that allowed for treatment during both acute and persistent stages of infection, the most effective combination in suppressing HIV infection was the continual use of both AZT and IFN-alpha at the highest tolerable doses. Knowledge of the efficacy of AZT on persistently infected cells will allow for the most effective design of clinical protocols.
Pincus
S H
SH
Laboratory of Microbial Structure and Function, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840.
Wehrly
K
K
D002460:Cell Line; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D015483:HIV Antibodies; D015658:HIV Infections / Q000188:drug therapy / Q000628:therapy; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000494:pharmacology*; D007370:Interferon Type I / Q000494:pharmacology*; D012276:Ricin / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
D015483:HIV Antibodies; D000922:Immunotoxins; D007370:Interferon Type I; D015215:Zidovudine; D012276:Ricin