AEGiS-06IAC: Effect of mode of azidothymidine (AZT) administration at early stages of retroviral friend virus infection in mice.

6th International AIDS Conference

San Francisco, California, USA — June 20-23, 1990

Effect of mode of azidothymidine (AZT) administration at early stages of retroviral friend virus infection in mice.

Int Conf AIDS 1990 Jun 20-23; 6:330 (abstract no. 1066)
Sinet M, Desforges B, Launay O, Sun F, Colin JN, Pocidalo JJ; INSERM U13, Hopital Claude Bernard, Paris, France

OBJECTIVE: To examine several doses, modes and routes of AZT administration for their ability to prevent dissemination of Friend virus inoculated in vivo.

METHODS: Viral infection of DBA2 mice was performed by retro-orbital inoculation of Friend leukemia virus complex at different titers (ranging between 20 and 500 focus forming units/ml). AZT was administered either in drinking water or subcutaneously (once or twice daily) at concentrations of 20, 40 or 80 mg/kg/day. Treatment was started either 1 h or 4 h after viral inoculation for 5 or 14 days. Treatment efficacy was evaluated by determination of splenic weight and infectious virus titer on day 14 and day 21 after inoculation. In some experiments, survival time after infection was also evaluated.

RESULTS: Friend virus infection causes erythroleukemia with splenomegaly (spleen weight ranging between 430 and 2000 mg 14 days post-inoculation), leading to death in 4 to 8 weeks. Main results are: 1) a significant reduction of splenomegaly with all regimens of AZT therapy: inhibition rate was at least 90% 14 days after infection, except for mice treated subcutaneously once daily (inhibition rate 50%). 2) influence of the delay between inoculation and treatment on efficacy of AZT chemoprophylaxis: in the group of mice treated 1 h post-inoculation with 40 mg/kg SC twice daily, 15/20 animals were still surviving 6 months later whereas only 7/20 animals survived in the group treated 4 h post-inoculation with the same mode of administration. 3) continuous administration of AZT in drinking water leads towards better results even with the 5 days therapy.

CONCLUSION: A short, early, continuous administration of AZT may prevent retroviral dissemination and development of disease in mice infected with Friend virus. This information may be considered for the prevention of HIV infection following accidental exposure.

Keywords: AEGIS, Friend murine leukemia virus, Retroviridae Infections, Zidovudine, HIV Infections, Spleen Focus-Forming Viruses, Leukemia, Erythroblastic, Acute, Mice, Inbred DBA, Antiviral Agents, Mice, Inbred C57BL, Spleen, Mice, Inbred Strains, Mice, Inbred BALB C, Mice, Animal, ICA6

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