Smith Jennifer A, Heffron Renee, Butler Ailsa R, Celum Connie, Baeten Jared M, Hallett Timothy B
Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
Department of Global Health, University of Washington, Seattle, USA.
Contraception. 2017 Apr;95(4):424-430. doi: 10.1016/j.contraception.2016.12.003. Epub 2016 Dec 28.
Some observational studies have suggested an association between the use of hormonal contraceptives (HC) and HIV acquisition. One major concern is that differential misreporting of sexual behavior between HC users and nonusers may generate artificially inflated risk estimates.
We developed an individual-based model that simulates the South African HIV serodiscordant couples analyzed for HC-HIV risk by Heffron et al. (2012). We varied the pattern of misreporting condom use between HC users and nonusers and reproduced the trial data under the assumption that HC use is not associated with HIV risk. The simulated data were analyzed using Cox proportional hazards models, adjusting for the reported level of condom use.
If HC users overreport condom use more than nonusers, an apparent excess risk could be observed even without any biological effect of HC on HIV acquisition. With 45% overreporting by HC users (i.e., 9 out of every 20 sex acts reported with condoms are actually unprotected) and accurate condom reporting by nonusers, a true null effect can be inflated to give an observed hazard ratio (HR̂) of 2.0. In a different population with lower overall reported condom use, artificially high HR̂s can only be generated if non-HC users underreport condom use.
Differential condom misreporting can theoretically produce inflated HR̂ values for an association between HC and HIV even without a true association. However, to produce a doubling of HIV risk that is entirely spurious requires substantially different levels of misreporting among HC users and nonusers, which may be unrealistic.
Considerably differential amounts of condom use misreporting by HC users and nonusers would be needed to produce entirely spurious observed levels of excess HIV acquisition risk among HC users when there is actually no true association.
一些观察性研究表明，使用激素避孕药（HC）与感染艾滋病毒之间存在关联。一个主要担忧是，HC使用者和非使用者在性行为报告上的差异可能会导致风险估计值被人为夸大。
我们开发了一个基于个体的模型，该模型模拟了Heffron等人（2012年）分析的南非艾滋病毒血清学不一致的夫妇的HC - 艾滋病毒风险情况。我们改变了HC使用者和非使用者在避孕套使用报告模式上的差异，并在假设HC使用与艾滋病毒风险无关的情况下重现了试验数据。使用Cox比例风险模型对模拟数据进行分析，并根据报告的避孕套使用水平进行调整。
如果HC使用者比非使用者更多地过度报告避孕套使用情况，那么即使HC对艾滋病毒感染没有任何生物学影响，也可能会观察到明显的额外风险。当HC使用者过度报告45%（即每报告20次性行为中有9次使用避孕套的实际情况是未采取保护措施）且非使用者准确报告避孕套使用情况时，真实的零效应可能会被夸大，从而得出观察到的风险比（HR̂）为2.0。在另一个总体报告的避孕套使用率较低的人群中，只有当非HC使用者少报避孕套使用情况时，才会产生人为的高HR̂值。
理论上，即使没有真正的关联，避孕套报告差异也可能导致HC与艾滋病毒之间关联的HR̂值被夸大。然而，要产生完全虚假的艾滋病毒风险翻倍情况，需要HC使用者和非使用者之间存在显著不同的误报水平，这可能不太现实。
当实际上不存在真正关联时，要在HC使用者中产生完全虚假的观察到的额外艾滋病毒感染风险水平，需要HC使用者和非使用者在避孕套使用误报数量上有相当大的差异。
