Postexposure chemoprophylaxis with ZDV or ZDV combined with interferon-alpha: failure after inoculating rhesus monkeys with a high dose of SIV.
Presently, no information is available regarding the efficacy of chemoprophylaxis in controlled human trials following accidental exposure to the human immunodeficiency virus (HIV). Using the closely related simian immunodeficiency virus (SIV) in rhesus monkeys, which develop a disease closely resembling human AIDS, we tested the efficacy of either single-agent 3'-azido-3'-deoxythymidine (ZDV) or the combination of ZDV plus recombinant human interferon-alpha (IFN-alpha). Treatment was started 3 h following inoculation of a high dose of SIV and continued for 21 days. SIV-inoculated control animals remained untreated. Virus was recovered from all monkeys on day 8, and by week 7 all had seroconverted. In contrast to monkeys treated with ZDV alone, animals given combination therapy had lower levels of p27 gag antigen compared to untreated controls on day 8 (p = 0.043). We conclude that neither treatment regimen could prevent infection after high-dose virus exposure; however, combination therapy may have depressed the level of virus replication more effectively than ZDV alone.
Fazely
F
F
Laboratory of Viral Pathogenesis, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Haseltine
W A
WA
Rodger
R F
RF
Ruprecht
R M
RM
D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D007370:Interferon Type I / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008253:Macaca mulatta; D008297:Male; D011994:Recombinant Proteins; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects*; D015215:Zidovudine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
D007370:Interferon Type I; D011994:Recombinant Proteins; D015215:Zidovudine