AEGiS-11IAC: In vivo antiviral activity of didanosine evaluated in the model of macaques infected by a pathogenic isolate of SIVmac251.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

In vivo antiviral activity of didanosine evaluated in the model of macaques infected by a pathogenic isolate of SIVmac251.

Int Conf AIDS 1996 Jul 7-12; 11:439 (abstract no. Pub.A.1009)
Franck M, Cheret A, Caufour P, Neildez O, Theodoro F, Vaslin B, Clayette P, Le Grand R, Dormontd; Service de Neurovirologie, Commissariat a l'Energie Atomique, DRM, DSV, SSA, France. Fax: (33-1) 46 54 77 26.

OBJECTIVES: To evaluate the antiviral efficacy of didanosine during the acute experimental infection of macaques with a pathogenic isolate of simian immunodeficiency virus (SIVmac251). Materials and methods: two groups of 4 and 2 cynomolgus macaques were treated by three daily subcutaneous injections of didanosine with the respective doses of 10.6 and 30 mg/kg/day of didanosine (ddI). Six animals were treated with the same schedule with a placebo. Treatment started 4 days before SIV inoculation, and was maintained until day 28 p.i. All macaques were inoculated by the intravenous route with 4 AID 50 of a cell-free virus stock containing a pathogenic isolate of SIVmac251 grown in monkey PBMCs. Classical hematological parameters, cell-associated virus load, p27 antigenemia, plasma anti-SIV antibodies and the presence of provirus in PBMC were followed every 3 days during the month following SIV inoculation.

RESULTS: Didanosine did not affect the hematological parameters even when a high dose was used. The monkeys treated with the dose of 10.6 mg/kg were infected by SIV as evidenced by PCR run on PBMC. However P27 antigenemia was enterely erased, cell-associated virus loads and plasma antibody concentration were significantly reduced. The monkeys treated with 30 mg/kg/day were completely protected as demonstrated by all criteria of diagnosis of SIV infection including nested PCR run on PBMC and lymph nodes.

CONCLUSION: Didanosine represents a good candidate for the treatment of accidental lab workers contamination as suggested by the complete protection of SIV infection of macaques with the high dose of drug. We plan to evaluate the effect of ddI during chronic SIV infection of macaques in association with other anti-retroviral molecules.

Keywords: AEGIS, Didanosine, SIV, Macaca, Viral Load, Zidovudine, Reverse Transcriptase Inhibitors, Antiviral Agents, Animal, ICA11

960707
PubA1009