Simian immunodeficiency virus (SIV) infection of infant rhesus macaques as a model to test antiretroviral drug prophylaxis and therapy: Oral 3'-azido- 3'-deoxythymidine prevents SIV infection

K. K.A. Van Rompay, Marta Marthas, R. A. Ramos, C. P. Mandell, E. K. McGowan, S. M. Joye, Niels C Pedersen

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Abstract

The prophylactic and therapeutic properties of 3'-azido-3'-deoxythymidine (AZT) against simian immunodeficiency virus (SIV) infection were tested in four 3-month-old rhesus macaques. The infant monkeys were inoculated intravenously with a low dose (1 to 10 100% animal infectious doses) of uncloned SIV(mac). The monkeys were treated orally with 50 mg of AZT per kg of body weight every 8 h; two animals were started on treatment 2 h prior to virus inoculation, and two animals were started on treatment 6 weeks later. All four animals were treated for a period of 6 to 10 weeks. Outward signs of AZT toxicity were absent, but a mild macrocytic anemia occurred soon after therapy was started and resolved shortly after it was discontinued. The two infants that were begun on AZT treatment 2 h prior to virus inoculation never became infected, as demonstrated by the inability to detect cell-free or cell-associated virus in the blood, proviral DNA in peripheral blood mononuclear cells, or anti-SIV antibodies. AZT administration over a 10-week period had no detectable effect on the course of disease in the two animals that were begun on treatment after the infection had been established. In addition to demonstrating the prophylactic effect of AZT against low-dose SIV exposure, the study demonstrated the ease with which infant rhesus macaques can be used for antiretroviral drug testing.

Original languageEnglish (US)
Pages (from-to)2381-2386
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume36
Issue number11
StatePublished - 1992

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Simian Immunodeficiency Virus
Zidovudine
Virus Diseases
Macaca mulatta
Drug Therapy
Haplorhini
Therapeutics
Macrocytic Anemia
Viruses
Satellite Viruses
Blood Cells
Body Weight
Antibodies
DNA
Infection
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Simian immunodeficiency virus (SIV) infection of infant rhesus macaques as a model to test antiretroviral drug prophylaxis and therapy : Oral 3'-azido- 3'-deoxythymidine prevents SIV infection. / Van Rompay, K. K.A.; Marthas, Marta; Ramos, R. A.; Mandell, C. P.; McGowan, E. K.; Joye, S. M.; Pedersen, Niels C.

In: Antimicrobial Agents and Chemotherapy, Vol. 36, No. 11, 1992, p. 2381-2386.

Research output: Contribution to journalArticle

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abstract = "The prophylactic and therapeutic properties of 3'-azido-3'-deoxythymidine (AZT) against simian immunodeficiency virus (SIV) infection were tested in four 3-month-old rhesus macaques. The infant monkeys were inoculated intravenously with a low dose (1 to 10 100{\%} animal infectious doses) of uncloned SIV(mac). The monkeys were treated orally with 50 mg of AZT per kg of body weight every 8 h; two animals were started on treatment 2 h prior to virus inoculation, and two animals were started on treatment 6 weeks later. All four animals were treated for a period of 6 to 10 weeks. Outward signs of AZT toxicity were absent, but a mild macrocytic anemia occurred soon after therapy was started and resolved shortly after it was discontinued. The two infants that were begun on AZT treatment 2 h prior to virus inoculation never became infected, as demonstrated by the inability to detect cell-free or cell-associated virus in the blood, proviral DNA in peripheral blood mononuclear cells, or anti-SIV antibodies. AZT administration over a 10-week period had no detectable effect on the course of disease in the two animals that were begun on treatment after the infection had been established. In addition to demonstrating the prophylactic effect of AZT against low-dose SIV exposure, the study demonstrated the ease with which infant rhesus macaques can be used for antiretroviral drug testing.",
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