Potential risks and benefits of HIV treatment simplification: a simulation model of a proposed clinical trial.
Potential risks and benefits of HIV treatment simplification: a simulation model of a proposed clinical trial.
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HIV 治疗简化的潜在风险和益处：拟议临床试验的模拟模型。
DOI：
10.1086/521933
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Freedberg,KennethA
中科院分区：
文献类型：
--
作者：
Schackman,BruceR;Scott,CallieA;Sax,PaulE;Losina,Elena;Wilkin,TimothyJ;McKinnon,JohnE;Swindells,Susan;Weinstein,MiltonC;Freedberg,KennethA
背景在最近的研究中，在接受初始3种药物抗逆转录病毒方案时实现人类免疫缺陷病毒（HIV）RNA水平抑制的受试者在接受单独“加强”蛋白酶抑制剂（PI）治疗时成功维持抑制。我们预测了这种治疗简化策略的长期结果，以告知拟议的多中心随机临床试验的设计。我们使用已发表的研究来评估简化策略的一系列HIV药物方案的疗效、不良反应和成本，并与当前标准治疗（SOC）策略的结果进行比较。使用已发表的HIV疾病模拟模型，我们预测了每种策略的预期寿命、贴现质量调整预期寿命（QALE）和贴现终身医疗成本。与SOC受试者相比，在简化方案失败时未发生PI耐药HIV感染的受试者的预期寿命（27.9 vs. 27.1年）和QALE（14.9 vs. 14.7年）更长，因为他们接受了额外的治疗线，对未来的治疗选择没有负面影响。简化策略的QALE仍然高于SOC，除非接受简化方案时发生病毒学失败的患者中有很大一部分发生PI耐药。根据简化方案失败的概率，即使HIV在42%-70%的受试者中产生PI耐药性，也能保持优势。简化战略的预计终身成本比SOC战略低26，500 - 72，400美元。与SOC联合治疗相比，涉及单独使用加强PI的HIV治疗简化策略可能导致总体生存期更长，成本更低，因为简化策略可能增加额外的治疗线。简化方案治疗期间出现PI耐药的风险是该策略可行性的关键决定因素。
Background. In recent studies, subjects who had achieved suppression of the human immunodeficiency virus (HIV) RNA level while receiving an initial 3-drug antiretroviral regimen successfully maintained suppression while receiving treatment with a “boosted” protease inhibitor (PI) alone. We projected the long-term outcomes of this treatment simplification strategy to inform the design of a proposed multicenter, randomized clinical trial.Methods. We used published studies to estimate the efficacy, adverse effects, and cost of a sequence of HIV drug regimens for the simplification strategy, compared with those outcomes for the current standard-of-care (SOC) strategy. Using a published simulation model of HIV disease, we projected life expectancy, discounted quality-adjusted life expectancy (QALE), and discounted lifetime medical costs for each strategy.Results. Subjects who have not developed PI-resistant HIV infection at the time of failure of the simplification regimen have a greater life expectancy (27.9 vs. 27.1 years) and QALE (14.9 vs. 14.7 years), compared with SOC subjects, because they receive an additional line of therapy without negative consequences for future treatment options. The QALE for the simplification strategy remains higher than that for the SOC, unless a large proportion of patients experiencing virologic failure while receiving the simplification regimen develop PI resistance. Depending on the probability of simplification regimen failure, the advantage is maintained even if HIV develops PI resistance in 42%–70% of subjects. Projected lifetime costs are $26,500–$72,400 per person lower for the simplification strategy than for the SOC strategy.Conclusions. An HIV treatment simplification strategy involving use of a boosted PI alone may lead to longer survival overall at lower cost, compared with the SOC combination therapy, because the simplification strategy potentially adds an additional line of therapy. The risk of emergence of PI resistance during treatment with a simplified regimen is a critical determinant of the viability of this strategy.
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DOI：
10.1001/jama.296.7.806
发表时间：
2006
期刊：
JAMA
影响因子：
--
作者：
Swindells,Susan;DiRienzo,AGregory;Wilkin,Timothy;Fletcher,CourtneyV;Margolis,DavidM;Thal,GaryD;Godfrey,Catherine;Bastow,Barbara;Ray,MGraham;Wang,Hongying;Coombs,RobertW;McKinnon,John;Mellors,JohnW;AIDSClinicalTrialsGrou
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AIDSClinicalTrialsGrou
影响因子：
158.5
作者：
Albrecht, MA;Bosch, RJ;Katzenstein, DA
通讯作者：
Katzenstein, DA
蛋白酶抑制剂失败后抗逆转录病毒治疗的有效性：分析概述。
DOI：
10.1086/420930
发表时间：
2004
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
影响因子：
--
作者：
Losina,Elena;Islam,Runa;Pollock,AlisonC;Sax,PaulE;Freedberg,KennethA;Walensky,RochelleP
通讯作者：
Walensky,RochelleP
DOI：
10.1186/cc2162
发表时间：
2003-06
期刊：
Critical care (London, England)
影响因子：
--
作者：
Claessens YE;Chiche JD;Mira JP;Cariou A
通讯作者：
Cariou A
影响因子：
6.4
作者：
Colonno, R;Rose, R;Friborg, J
通讯作者：
Friborg, J