Paltiel A David, Zheng Amy, Weinstein Milton C, Gaynes Melanie R, Wood Robin, Freedberg Kenneth A, Sax Paul E, Walensky Rochelle P
Yale School of Public Health, New Haven, Connecticut.
Medical Practice Evaluation Center and Divisions of.
Open Forum Infect Dis. 2017 Apr 22;4(2):ofx081. doi: 10.1093/ofid/ofx081. eCollection 2017 Spring.
Reports of a single case of human immunodeficiency virus (HIV) eradication suggest that elimination of HIV from individuals is possible. Anticipating both increased research funding and the development of effective, durable cure technologies, we describe the circumstances under which a cure might improve survival and be cost-effective in South Africa.
We adapted a simulation model comparing a hypothetical cure strategy ("Cure") to the standard of care, lifetime antiretroviral therapy ("LifetimeART") among adherent South Africans (58% female; mean age 33.8 years; mean CD4 257/µL; virologic suppression ≥1 year). We portrayed cure as a single intervention, producing sustained viral eradication without ART. We considered both a plausible, more imminently achievable "Baseline Scenario" and a more aspirational "Optimistic Scenario". Inputs (Baseline/Optimistic) included the following: 50%/75% efficacy; 0.6%/0.0% fatal toxicity; 0.37%/0.085% monthly relapse over 5 years (0.185%/0.0425% per month thereafter); and $2000/$500 cost. These inputs were varied extensively in sensitivity analysis.
At baseline, Cure was "dominated," yielding lower discounted life expectancy (19.31 life-years [LY] vs 19.37 LY) and greater discounted lifetime costs ($13 800 vs $13 700) than LifetimeART. Under optimistic assumptions, Cure was "cost-saving," producing greater survival (19.91 LY) and lower lifetime costs ($11 000) than LifetimeART. Findings were highly sensitive to data assumptions, leaving little middle ground where a tradeoff existed between improved survival and higher costs.
Only under the most favorable performance assumptions will an HIV cure strategy prove clinically and economically justifiable in South Africa. The scientific pursuit of a cure should not undermine continued expansions of access to proven, effective, and cost-effective ART.
关于单一例人类免疫缺陷病毒（HIV）根除的报告表明，从个体中消除HIV是有可能的。鉴于研究资金的增加以及有效、持久的治愈技术的发展，我们描述了在南非治愈可能改善生存并具有成本效益的情况。
我们采用了一个模拟模型，将一种假设的治愈策略（“治愈”）与南非坚持治疗的人群（58%为女性；平均年龄33.8岁；平均CD4为257/µL；病毒学抑制≥1年）中的标准治疗方案，即终身抗逆转录病毒治疗（“终身ART”）进行比较。我们将治愈描述为一种单一干预措施，无需抗逆转录病毒治疗即可实现持续的病毒根除。我们考虑了一个看似合理、更有望立即实现的“基线情景”和一个更具抱负的“乐观情景”。输入参数（基线/乐观）包括以下内容：疗效50%/75%；致命毒性0.6%/0.0%；5年内每月复发率0.37%/0.085%（此后每月0.185%/0.0425%）；成本2000美元/500美元。在敏感性分析中对这些输入参数进行了广泛的变化。
在基线情况下，“治愈”方案被“主导”，与终身ART相比，贴现预期寿命更低（19.31生命年[LY]对19.37 LY），贴现终身成本更高（13800美元对13700美元）。在乐观假设下，“治愈”方案是“节省成本的”，与终身ART相比，生存率更高（19.91 LY），终身成本更低（11000美元）。研究结果对数据假设高度敏感，几乎没有在改善生存和更高成本之间存在权衡的中间地带。
只有在最有利的性能假设下，HIV治愈策略在南非才会在临床和经济上被证明是合理的。对治愈方法的科学追求不应破坏继续扩大获得已证实、有效且具有成本效益的抗逆转录病毒治疗的机会。
