Division of Infectious Diseases, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2007 Sep 19;2(9):e875. doi: 10.1371/journal.pone.0000875.
The potential impact of pre-exposure chemoprophylaxis (PrEP) on heterosexual transmission of HIV-1 infection in resource-limited settings is uncertain.
METHODOLOGY/PRINCIPLE FINDINGS: A deterministic mathematical model was used to simulate the effects of antiretroviral PrEP on an HIV-1 epidemic in sub-Saharan Africa under different scenarios (optimistic, neutral and pessimistic) both with and without sexual disinhibition. Sensitivity analyses were used to evaluate the effect of uncertainty in input parameters on model output and included calculation of partial rank correlations and standardized rank regressions. In the scenario without sexual disinhibition after PrEP initiation, key parameters influencing infections prevented were effectiveness of PrEP (partial rank correlation coefficient (PRCC) = 0.94), PrEP discontinuation rate (PRCC = -0.94), level of coverage (PRCC = 0.92), and time to achieve target coverage (PRCC = -0.82). In the scenario with sexual disinhibition, PrEP effectiveness and the extent of sexual disinhibition had the greatest impact on prevention. An optimistic scenario of PrEP with 90% effectiveness and 75% coverage of the general population predicted a 74% decline in cumulative HIV-1 infections after 10 years, and a 28.8% decline with PrEP targeted to the highest risk groups (16% of the population). Even with a 100% increase in at-risk behavior from sexual disinhibition, a beneficial effect (23.4%-62.7% decrease in infections) was seen with 90% effective PrEP across a broad range of coverage (25%-75%). Similar disinhibition led to a rise in infections with lower effectiveness of PrEP (< or = 50%).
CONCLUSIONS/SIGNIFICANCE: Mathematical modeling supports the potential public health benefit of PrEP. Approximately 2.7 to 3.2 million new HIV-1 infections could be averted in southern sub-Saharan Africa over 10 years by targeting PrEP (having 90% effectiveness) to those at highest behavioral risk and by preventing sexual disinhibition. This benefit could be lost, however, by sexual disinhibition and by high PrEP discontinuation, especially with lower PrEP effectiveness (< or = 50%).
在资源有限的环境下，暴露前化学预防（PrEP）对艾滋病毒 1 型感染异性传播的潜在影响尚不确定。
方法/原理发现：采用确定性数学模型，在不同情景（乐观、中性和悲观）下，模拟了抗逆转录病毒 PrEP 对撒哈拉以南非洲艾滋病毒 1 型流行的影响，同时考虑了和不考虑性行为抑制。敏感性分析用于评估输入参数的不确定性对模型输出的影响，包括部分秩相关系数和标准化秩回归的计算。在没有性行为抑制的情况下，预防感染的关键参数包括 PrEP 的有效性（部分秩相关系数（PRCC）=0.94）、PrEP 停药率（PRCC=-0.94）、覆盖率（PRCC=0.92）和达到目标覆盖率的时间（PRCC=-0.82）。在有性行为抑制的情况下，PrEP 的有效性和性行为抑制的程度对预防产生了最大的影响。如果 PrEP 效果为 90%、普通人群覆盖率为 75%，则在乐观情景下，10 年后累积艾滋病毒 1 型感染人数将减少 74%，而将 PrEP 针对高危人群（占总人口的 16%），则减少 28.8%。即使高危行为因性行为抑制而增加 100%，在广泛的覆盖率（25%-75%）范围内，具有 90%有效性的 PrEP 也能产生有益效果（感染减少 23.4%-62.7%）。PrEP 效果较低（≤50%）时，类似的抑制会导致感染增加。
结论/意义：数学模型支持 PrEP 的潜在公共卫生效益。在南部撒哈拉以南非洲，通过将 PrEP（效果 90%）针对行为风险最高的人群，并防止性行为抑制，在 10 年内可避免约 270 万至 320 万例新的艾滋病毒 1 型感染。然而，性行为抑制和 PrEP 停药率高，尤其是 PrEP 效果较低（≤50%），会使这一效益丧失。
