Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Institute for Global Health, University College London, London, UK.
Lancet HIV. 2020 Nov;7(11):e791-e796. doi: 10.1016/S2352-3018(20)30192-2.
Trials of candidate agents for HIV pre-exposure prophylaxis (PrEP) might randomly assign participants to be given a new PrEP agent or oral coformulated tenofovir disoproxil fumarate plus emtricitabine. This design presents unique challenges in interpretation. First, with two active arms, HIV incidence might be low. Second, the effectiveness of tenofovir disoproxil fumarate plus emtricitabine varies across populations; thus, similar HIV incidence between groups could be consistent with a wide range of effectiveness for the new PrEP. We propose a two-part approach to trial results. First, we use Bayesian methods to incorporate assumptions about the background incidence of HIV in the trial in the absence of PrEP, possibly augmented by external data. On the basis of the estimated background incidence, we estimate and compare the number of averted (or prevented) HIV infections in each of the two trial groups, calculating the averted infections ratio. We apply these methods to a completed trial of tenofovir alafenamide plus emtricitabine for PrEP. Our framework shows that leveraging external information to estimate averted infections and the averted infections ratio enhances the efficiency and interpretation of active-controlled PrEP trials.
候选抗 HIV 暴露前预防（PrEP）药物的试验可能会随机分配参与者接受新的 PrEP 药物或口服复方替诺福韦酯富马酸丙酚替诺福韦加恩曲他滨。这种设计在解释上带来了独特的挑战。首先，由于有两个活性药物组，HIV 发病率可能较低。其次，替诺福韦酯富马酸丙酚替诺福韦加恩曲他滨在不同人群中的有效性存在差异；因此，两组之间相似的 HIV 发病率可能与新 PrEP 的广泛有效性一致。我们提出了一种两部分的试验结果分析方法。首先，我们使用贝叶斯方法，在没有 PrEP 的情况下，根据试验中 HIV 的背景发病率假设（可能通过外部数据进行增强）。基于估计的背景发病率，我们估计和比较两个试验组中每个组避免（或预防）的 HIV 感染数量，计算避免感染的比例。我们将这些方法应用于替诺福韦艾拉酚胺加恩曲他滨用于 PrEP 的完成试验。我们的框架表明，利用外部信息来估计避免感染和避免感染的比例，可以提高活性对照 PrEP 试验的效率和解释能力。
