Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
Animal model for anti-viral therapy: effect of AZT treatment on cellular and seric viral loads during early stages of SIVmac251 infection of macaques.
Symp Nonhum Primate Models AIDS. 1993 Sep 19-22;11:abstract no. 59. Unique Identifier : AIDSLINE PRIM11/94191654 Le Grand R; Clayette P; Vaslin B; Noack O; Theodoro F; Roques P; Dormont D; Laboratoire de Neuropathologie Experimentale et Neurovirologie,; CEA/SSA, Fontenay aux Roses, France.
Abstract:
OBJECTIVES: To evaluate the efficiency of prophylactic treatment with AZT during primo-infection of SIVmac251 (monkey PBL grown virus stock) inoculated cynomolgus monkeys. MATERIALS AND METHODS: Two groups of four Macaca fascicularis were treated either with AZT (Three daily subcutaneous injections of 15 mg/kg) or Placebo during seven days prior to intravenous injection of 4 MID50 SIVmac251 stock. The viral inoculum was provided by a cell-free supernatant of a coculture of rhesus PBMCs with a spleen homogenate of an SIVmac251 infected macaque. Treatment lasted 30 days after virus inoculation. Blood samples were drawn every two or three days for the evaluation of P27 antigenemia, seric viremia by coculture and cellular viremia. Seric viremia was performed by infection of 25 x 10(3) CEMX174 cells with serial three-fold dilutions of monkey sera; the TCID50 was determined by syncytia detection at days 5 and 7 of culture. Cellular viremia were performed by co-cultivating serial dilutions of fresh ficoll isolated monkey PBMCs with 120 x 10(3) CEMX174 cells. Titers were given as the TCID50 determined by syncytia detection and SIV specific ELISA at day 7 of culture. Hematologic parameters and detection of seric response to SIV were monitored weekly. RESULTS: AZT clearly modified hematologic parameters after two weeks of treatment confirming its low toxicity at high dose administrations. Since day 12 post-infection three out of four control monkeys developed high plasma p27 antigenemia, whereas it remains undetectable for the four AZT treated animals. The four control monkeys exhibited positive cellular viremia since day 7 and 9 post infection with titers ranging between 10(2) and 10(3) TCID50. Two of the AZT treated animals remain negative for cellular viremia until day 15 post infection, at that time titers were lower than 10(1). The two other AZT treated monkeys exhibited positive cocultures since days 7 and 9 post infection with titers ranging from 10(1) to 10(2). CONCLUSION: Intravenous infection with low doses of pathogenic monkey PBMC-grown SIVmac251 could not be totally prevented by AZT treatment. However, during primo-infection, viral load could significatively be reduced as determined by plasma antigenemia and quantitative cellular viremia assay. Seric viremia are under evaluation.
Keywords: Animal Disease Models, Animal Lymphocytes/MICROBIOLOGY Macaca fascicularis Simian Acquired Immunodeficiency Syndrome/BLOOD/*DRUG THERAPY/ PHYSIOPATHOLOGY SIV/ISOLATION & PURIF Viremia/DRUG THERAPY/PREVENTION & CONTROL Zidovudine/*THERAPEUTIC USE ABSTRACT 940730
M9470864
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Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
