Krakovska O, Wahl L M
Department of Applied Mathematics, University of Western Ontario, London, Ont., Canada N6A 5B7.
J Theor Biol. 2007 Jun 7;246(3):499-509. doi: 10.1016/j.jtbi.2006.12.038. Epub 2007 Jan 23.
Drug therapies aimed at suppressing the human immunodeficiency virus (HIV) are highly effective, often reducing the viral load to below the limits of detection for years. Adherence to such antiviral regimens, however, is typically far from ideal. We have previously developed a model that predicts optimal treatment regimens by weighing drug toxicity against CD4+ T-cell counts, including the probability that drug resistance will emerge. We use this model to investigate the influence of adherence on therapy benefit. For a drug with a given half-life, we compare the effects of varying the dose amount and dose interval for different rates of adherence, and compute the optimal dose regimen for adherence between 65% and 95%. Our results suggest that for optimal treatment benefit, drug regimens should be adjusted for poor adherence, usually by increasing the dose amount and leaving the dose interval fixed. We also find that the benefit of therapy can be surprisingly robust to poor adherence, as long as the dose interval and dose amount are chosen accordingly.
旨在抑制人类免疫缺陷病毒(HIV)的药物疗法非常有效,通常能将病毒载量降低到检测限以下数年。然而,对抗病毒治疗方案的依从性通常远不理想。我们之前开发了一个模型,通过权衡药物毒性与CD4 + T细胞计数,包括出现耐药性的概率,来预测最佳治疗方案。我们使用这个模型来研究依从性对治疗益处的影响。对于一种具有给定半衰期的药物,我们比较了不同依从率下改变剂量和给药间隔的效果,并计算出65%至95%依从性的最佳给药方案。我们的结果表明,为了获得最佳治疗益处,对于依从性差的情况,应调整药物治疗方案,通常是增加剂量并保持给药间隔不变。我们还发现,只要相应地选择给药间隔和剂量,治疗益处对于依从性差的情况可能会惊人地稳健。