Prevention of vaginal simian immunodeficiency virus transmission in macaques by postexposure prophylaxis with zidovudine, lamivudine and indinavir
Prevention of vaginal simian immunodeficiency virus transmission in macaques by postexposure prophylaxis with zidovudine, lamivudine and indinavir
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DOI：
10.1097/qad.0b013e328321302d
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发表时间：
2009-02-20
期刊：
影响因子：
3.8
通讯作者：
Le Grand, Roger
中科院分区：
文献类型：
--
作者：
Bourry, Olivier;Brochard, Patricia;Le Grand, Roger
目的：评价齐多夫定(ZDV)、拉米夫定(3TC)和吲哚那韦(IDV)联合预防感染HIV的效果。设计：雌性食蟹猴阴道内感染HIV.mac251。每组6只动物，每日2次口服ZDV(4.5 mg/kg)、3TC(2.5 mg/kg)、IDV(20 mg/kg)或皮下注射ZDV(4.5 mg/kg)、3TC(2.5 mg/kg)或更大剂量的IDV(60 mg/kg)，每日2次。如果所有药物都是口服的，抗逆转录病毒协会保护了六只动物中的一只，如果皮下注射ZDV和3TC，口服三倍剂量的IDV，则保护了六只动物中的四只。在受感染的动物中，与服用安慰剂的动物相比，接受治疗的动物的病毒血症显著延迟和降低，至少在中期内，接受治疗的动物保持了较高的CD4细胞计数。在接受相同处理的猕猴身上进行的抗逆转录病毒剂量表明，保护效果可能与抗逆转录病毒血浆浓度有关。结论：本研究首次在猕猴身上表明，建议人类使用的暴露后预防措施可能在阴道暴露后有效。药代动力学参数的改善显著提高了治疗效率。(C)2009年Wolters Kluwer Health垂直酒吧Lippincott Williams&Wilkins
Objective: To evaluate the efficacy of postexposure prophylaxis with a combination of zidovudine (ZDV), lamivudine (3TC) and indinavir (IDV), after vaginal exposure to HIV.Design: Experimental intravaginal exposure of female cynomolgus macaques to HIV.mac251.Methods: ZDV/3TC/IDV treatment was initiated 4 h after exposure and continued for 28 days. Groups of six animals received a placebo or a combination of oral ZDV (4.5 mg/kg), 3TC (2.5 mg/kg) and IDV (20 mg/kg) twice daily or Subcutaneous ZDV (4.5 mg/kg) and 3TC (2.5 mg/kg) twice daily, and a higher dose of IDV (60 mg/kg) administered orally twice daily.Results: In the placebo group, all animals were infected. Antiretroviral association protected one of the six animals if all drugs were administered orally and four of the six animals if ZDV and 3TC were administered subcutaneously and IDV was given orally at triple dose. In infected animals, viremia was significantly delayed and lowered in treated animals than in animals given placebo, and high CD4 cell counts were maintained in the treated animals, at least in the medium term. Antiretroviral dosages made in macaques receiving the same treatments showed that protection efficacy could be linked to antiretroviral plasmatic concentration.Conclusion: This study shows, for the first time in macaques, that the postexposure prophylaxis recommended for humans may be effective after vaginal exposure. Improvements in pharmacokinetic parameters significantly increased treatment efficiency. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins