Live attenuated HIV vaccines: Predicting the tradeoff between efficacy and safety
Live attenuated HIV vaccines: Predicting the tradeoff between efficacy and safety
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DOI：
10.1073/pnas.061029998
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发表时间：
2001-03-13
影响因子：
11.1
通讯作者：
Mills, J
中科院分区：
文献类型：
--
作者：
Blower, SM;Koelle, K;Mills, J
控制艾滋病毒流行的减毒活疫苗的效用正在辩论中。减毒活艾滋病毒疫苗(LAHV)在预防感染野生型毒株方面可能非常有效，但可能不是完全安全的，因为减毒毒株可能会在一些接种疫苗的个人中导致艾滋病。我们提出了一个理论框架，用于评估疫苗有效性(根据防止新的野生型毒株感染)和安全性(根据疫苗导致的艾滋病死亡)之间的权衡结果。我们使用我们的框架来预测，对于津巴布韦和泰国，1000种不同的LAHV(由有效性和安全性特征指定)的流行病学影响。我们预测，自相矛盾的是：(I)在传播率高的津巴布韦，LAHV将显著降低艾滋病死亡率，但(Ii)在泰国(传播率低)，完全相同的疫苗(根据有效性和安全性特征)将增加艾滋病死亡率。我们的结果表明，存在一个阈值传播率，它决定了任何给定的LAHV是有益的还是有害的影响。我们还确定了疫苗变态点，它是根据因疫苗毒株而进展为艾滋病的接种个体的比例来定义的。接种任何一种LAHV疫苗，如果在25年内导致超过5%的接种者进展为艾滋病，即使是50年后，也会在泰国导致变态(即增加每年的艾滋病死亡率)；这些疫苗将导致津巴布韦每年的艾滋病死亡率下降。
The utility of live attenuated vaccines for controlling HIV epidemics is being debated. Live attenuated HIV vaccines (LAHVs) could be extremely effective in protecting against infection with wild-type strains, but may not be completely safe as the attenuated strain could cause AIDS in some vaccinated individuals. We present a theoretical framework for evaluating the consequences of the tradeoff between vaccine efficacy (in terms of preventing new infections with wild-type strains) and safety (in terms of vaccine-induced AIDS deaths). We use our framework to predict, for Zimbabwe and Thailand, the epidemiological impact of 1,000 different (specified by efficacy and safety characteristics) LAHVs, We predict that paradoxically: (i) in Zimbabwe (where transmission is high) LAHVs would significantly decrease the AIDS death rate, but (ii) in Thailand (where transmission is low) exactly the same vaccines (in terms of efficacy and safety characteristics) would increase the AIDS death rate. Our results imply that a threshold transmission rate exists that determines whether any given LAHV has a beneficial or a detrimental impact, We also determine the vaccine perversity point, which is defined in terms of the fraction of vaccinated individuals who progress to AIDS as a result of the vaccine strain. Vaccination with any LAHV that causes more than 5% of vaccinated individuals to progress to AIDS in 25 years would, even 50 years later, lead to perversity (i.e., increase the annual AIDS death rate) in Thailand; these same vaccines would lead to decreases in the annual AIDS death rate in Zimbabwe.