Should expectations about the rate of new antiretroviral drug development impact the timing of HIV treatment initiation and expectations about treatment benefits?
Should expectations about the rate of new antiretroviral drug development impact the timing of HIV treatment initiation and expectations about treatment benefits?
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DOI：
10.1371/journal.pone.0098354
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Roberts MS
中科院分区：
文献类型：
--
作者：
Khademi A;Braithwaite RS;Saure D;Schaefer AJ;Nucifora K;Roberts MS
对艾滋病毒治疗决定的许多分析都假定有一个固定的艾滋病毒药物处方。然而，新药几乎每年批准两次，新药的供应速度可能影响治疗决定，特别是何时开始抗逆转录病毒疗法。确定考虑新药的可用性对ART最佳启动标准和HIV/AIDS患者结局的影响。我们增强了先前描述的启动ART的最佳时间的模拟模型，以纳入新的抗病毒药物的可用性。我们假设未来新药的可用率与过去新药的可用率相似，我们通过将统计模型拟合到1982-2010年的实际艾滋病毒药物批准数据来估计过去的可用率。然后，我们测试了新药的未来可用性是否会影响模型预测的基于临床结果启动ART的最佳时间，考虑200，350和500个细胞/mm 3的治疗启动阈值。我们还量化了新药未来可用性对预期寿命（LE）和质量调整预期寿命（QALE）的影响。在基础病例分析中，考虑到新药的可用性，将大多数患者的最佳起始CD 4阈值提高至500个细胞/mm 3。由于管道药物的可用性，预测的结局增益通常很小（小于1%），但对于高病毒载量的年轻患者，LE增加了4.9%（1.73年），QALE增加了8%（2.43 QALY），因为这些患者特别可能在死亡前用尽目前可用的ART方案。在敏感性分析中，增加新药的可用性并没有实质性地改变结果。降低未来ART药物的毒性有更大的潜力增加许多患者群体的获益，将QALE提高10%。未来可获得毒性较低的新ART药物，为大多数患者提供最佳治疗起始，并改善临床结局，特别是对于病毒载量较高的年轻患者。未来ART药物毒性的降低可能会影响最佳治疗的启动，并改善所有HIV患者的临床结局。
Many analyses of HIV treatment decisions assume a fixed formulary of HIV drugs. However, new drugs are approved nearly twice a year, and the rate of availability of new drugs may affect treatment decisions, particularly when to initiate antiretroviral therapy (ART). To determine the impact of considering the availability of new drugs on the optimal initiation criteria for ART and outcomes in patients with HIV/AIDS. We enhanced a previously described simulation model of the optimal time to initiate ART to incorporate the rate of availability of new antiviral drugs. We assumed that the future rate of availability of new drugs would be similar to the past rate of availability of new drugs, and we estimated the past rate by fitting a statistical model to actual HIV drug approval data from 1982–2010. We then tested whether or not the future availability of new drugs affected the model-predicted optimal time to initiate ART based on clinical outcomes, considering treatment initiation thresholds of 200, 350, and 500 cells/mm3. We also quantified the impact of the future availability of new drugs on life expectancy (LE) and quality-adjusted life expectancy (QALE). In base case analysis, considering the availability of new drugs raised the optimal starting CD4 threshold for most patients to 500 cells/mm3. The predicted gains in outcomes due to availability of pipeline drugs were generally small (less than 1%), but for young patients with a high viral load could add as much as a 4.9% (1.73 years) increase in LE and a 8% (2.43 QALY) increase in QALE, because these patients were particularly likely to exhaust currently available ART regimens before they died. In sensitivity analysis, increasing the rate of availability of new drugs did not substantially alter the results. Lowering the toxicity of future ART drugs had greater potential to increase benefit for many patient groups, increasing QALE by as much as 10%. The future availability of new ART drugs without lower toxicity raises optimal treatment initiation for most patients, and improves clinical outcomes, especially for younger patients with higher viral loads. Reductions in toxicity of future ART drugs could impact optimal treatment initiation and improve clinical outcomes for all HIV patients.
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DOI：
10.1097/qad.0b013e32834dce6e
发表时间：
2012-01-02
期刊：
AIDS (London, England)
影响因子：
--
作者：
Sloan CE;Champenois K;Choisy P;Losina E;Walensky RP;Schackman BR;Ajana F;Melliez H;Paltiel AD;Freedberg KA;Yazdanpanah Y;Cost-Effectiveness of Preventing AIDS Complications (CEPAC) investigators
通讯作者：
Cost-Effectiveness of Preventing AIDS Complications (CEPAC) investigators
影响因子：
39.2
作者：
Braithwaite, R. Scott;Roberts, Mark S.;Justice, Amy C.
通讯作者：
Justice, Amy C.
影响因子：
5.2
作者：
Braithwaite, R. S.;Shechter, S.;Justice, A. C.
通讯作者：
Justice, A. C.
影响因子：
168.9
作者：
Phillips, Andrew N.;Pillay, Deenan;Lundgren, Jens D.
通讯作者：
Lundgren, Jens D.
影响因子：
168.9
作者：
Harrington, M;Carpenter, CCJ
通讯作者：
Carpenter, CCJ