编者按：在第25届国际艾滋病大会上，加拿大疾病控制中心、英属哥伦比亚大学Troy Grennan教授领导的团队一项研究揭示了多西环素暴露前预防（DoxyPrEP）在降低HIV阳性男男性行为者细菌性性传播感染（STI）发病率方面的惊人成效。该研究发现，每日服用100 mg多西环素可显著降低梅毒、衣原体感染和淋病的发病率，总体降低率高达80%。这一突破性发现不仅为STI预防提供了新的策略，也为未来公共卫生政策制定提供了重要依据。随着更大规模临床试验的推进，多西环素有望成为STI预防领域的重要工具，为全球公共卫生安全贡献力量。《感染医线》特邀请Troy Grennan教授进行了专访。

 

01

《感染医线》：在这项研究中，DoxyPrEP在降低HIV阳性男男性行为者STI发病率方面，取得了哪些具体成效？

 

Grennan教授：在我们的研究中，我们发现DoxyPrEP（100 mg/d）能显著降低STI的发病率，如梅毒、衣原体感染和淋病。我们看到这些细菌性性传播感染的总体降低率约为80%，而将其按具体感染分类时，我们看到梅毒降低了79%，衣原体感染降低了92%，淋病降低了68%。

 

IIDF: In this study, what specific effects has doxycycline, as a pre exposure prophylactic (PrEP) drug, achieved in reducing the incidence rate of bacterial sexually transmitted infections (STI) among HIV positive men who have sex with men?

 

Dr Grennan: Thank you for the question. In our study, what we found was when doxycycline was used as PrEP (pre-exposure prophylaxis) daily at a dosage of 100mg, it significantly reduced the incidence of bacterial sexually transmitted infections (STIs), like syphilis, chlamydia and gonorrhea. We saw an overall reduction in these bacterial STIs of about 80%, and when you broke it down by specific infection, we saw a reduction of 79% in syphilis, 92% in chlamydia and 68% in gonorrhea.

 

02

《感染医线》：与安慰剂组相比，多西环素组在预防STI方面的优势主要体现在哪些方面？这些优势是否具有统计学显著性？

 

Grennan教授：上述研究结果，即STI感染率显著降低，是在将DoxyPEP与安慰剂进行对比的严格科学研究中得出的，包括总体降低率80%，以及梅毒降低79%、衣原体感染降低92%、淋病降低68%。这些具体的降低率，在与安慰剂进行对比时都显示出了统计学上的显著性。这一比较研究的设计确保了结果的准确性和可靠性。它为我们提供了有力的证据，表明多西环素PrEP在预防细菌性性传播感染方面具有显著效果。

 

然而，必须指出的是，这是一项规模很小的研究，仅纳入了52名受试者。这限制了结果的广泛适用性。因此，我们的主要目标是评估DoxyPEP在实际使用中的可行性和接受度，包括这种方法在实际应用中是否有良好的耐受性，受试者的依从性如何，这些都是我们迫切想要回答的主要问题。

 

未来的研究应该致力于验证这些初步发现，并进一步探索DoxyPEP在不同人群和背景下的效果。此外，我们还需要研究多西环素与其他预防措施（如安全套使用和教育宣传）的结合使用，以评估是否能提供更全面的保护。

 

IIDF: What are the main advantages of the doxycycline group in preventing STI compared to the placebo group? Are these advantages statistically significant?

 

Dr Grennan: So the numbers that I mentioned, the reductions, was when doxycycline PrEP was compared to placebo. All of those results I mentioned - the overall reduction of 80%, and the other specific reductions - were all statistically significant when comparing DoxyPrEP to placebo. That would be one of the advantages, at least in our study. The one thing I will say though is that this was a very small study. There were only 52 participants; it was a pilot study. The main question we aimed to answer with the study was one of feasibility. Was this acceptable? Was it well-tolerated? Did people find it easy to take? That was the main question that we asked. Although the STI reductions that we saw were still significant, they were our secondary questions for the study. I would say that for the purpose of extending these results and translating them for the public, we still need more data before we move forward with this as an intervention that everybody can use.

 

03

《感染医线》：结合您的临床经验，长期使用DoxyPEP其安全性如何？在提高STI预防策略的依从性方面，您认为面临哪些主要挑战，应如何解决？

 

Grennan教授：多西环素自20世纪60年代起就开始被广泛使用，作为医生和研究人员，我们对多西环素积累了丰富的经验，对其作用机制、人们的耐受性、副作用以及安全性等方面都有着深入的了解和认识。

 

一个值得关注的重点是，多西环素是少数几种能够长期使用，甚至长期大量使用的抗生素之一。时至今日，当人们出行至疟疾流行地区时，仍会经常选择使用多西环素来预防疟疾。此外，它还被广泛应用于治疗其他疾病，比如各种皮肤疾病，尤其是痤疮。在这些治疗场景下，多西环素经常被长期使用，有时甚至会持续数月，甚至超过一年或更久。因此，我们对于这种药物的安全性有着充分的信心，同时也对其可能产生的副作用有着清晰的了解。

 

众所周知，在服用多西环素后，一些患者可能会出现胃肠道症状，如烧心、胃痛，有时还会伴有腹泻。但值得庆幸的是，这些症状通常会随着时间的推移而自行消失。我们已经有了关于多西环素暴露后预防用药（DoxyPEP）的充分证据，证明其有效性和安全性。而我们目前的研究重点则放在了DoxyPrEP上。如果进一步的研究能够证实DoxyPrEP与DoxyPEP具有相似的疗效和安全性，那么这将为那些适合使用它的个体提供另一种重要的选择。

 

IIDF: Based on your clinical experience, what is the safety of long-term use of doxycycline as PrEP? What do you think are the main challenges in improving compliance with STI prevention strategies and how should they be addressed?

 

Dr Grennan: Collectively, as a community of physicians and researchers, we have a lot of experience with doxycycline. It is a medication that, in many parts of the world, has been around since the 1960s. It has been around for a very long time, so have a very good idea about how it works, how people tolerate it, what the side effects are, how safe it is. The other key thing is that it is one of the few antibiotics that has been used for a very long time, but has also been used for extended periods. It is often used, even still today, for prevention of malaria when people are traveling. It is used for other things, such as treatment of various skin conditions like acne. In these situations, it is often used for a very long time - many months, sometimes up to a year or more. So we have a very good idea of how safe this drug is, and we understand the side effect profile. We know that generally, there may be a little bit of GI symptoms, like heartburn, stomach ache and maybe some diarrhea, and that these will generally pass with time. In terms of your questions about adherence to the medication, the key thing that we need to think about when providing individuals with an option for STI prevention such as DoxyPrEP or DoxyPEP (which is the more established intervention), is that we need to provide choice. I think we already have very good evidence for DoxyPEP, which is post-exposure prophylaxis. Our study here is DoxyPrEP. If further research indicates that DoxyPrEP is a really good comparable option for DoxyPEP, then that will provide an additional choice for those individuals fin whom this would be a good option.

 

04

《感染医线》：您对未来进一步探索多西环素或其他PrEP药物在STI预防中的应用有何建议？同时，对于公共卫生部门，您有哪些具体的政策建议？

 

Grennan教授：目前，我们正在加拿大积极推进一项对DoxyPrEP的更大规模的研究——DISCO研究。这是一项面向加拿大全国性的临床试验，我们的目标是招募到560名受试者。在这项研究中，我们将受试者随机分配到两个不同的研究组。第一组是DoxyPrEP组，该组的受试者将按照我们的研究方案，每天服用多西环素。另一组则是与DoxyPEP进行比较的组，正如我之前所提到的，DoxyPEP是一种更为成熟且已得到广泛应用的干预措施，该组的受试者在接触后服用多西环素。

 

通过这项研究，我们希望能够更明确地确定下一步的研究方向。此外，还有很多未解之谜等待我们去揭开。特别是抗菌素耐药性这个问题，它的重要性不言而喻。到目前为止，无论是我们的研究还是其他已经完成的研究，都没有明确显示出抗菌素耐药性可能的发展方向。但这是一个绝对需要我们密切关注并进一步研究的重要问题。

 

IIDF: Do you have any suggestions for further exploring the use of doxycycline or other PrEP drugs in STI prevention in the future? Meanwhile, what specific policy recommendations do you have for the public health sector?

 

Dr Grennan: As I mentioned, I think the next steps are doing a larger study on DoxyPrEP, which we happen to be doing in Canada right now. In Canada, we are currently running a study called DISCO (and you can see it on my poster). It is a clinical trial that we are recruiting across Canada. We are aiming to recruit 560 people. What we are doing in that study is randomizing them to one of two study arms. The first arm is the DoxyPrEP arm, where people will get daily doxycycline, as our study did. The other arm is comparing that to DoxyPEP, which as I mentioned is the more established intervention, and is where people take doxycycline after an exposure. I would say that is number one for where we want to head in the future for figuring out what is next. Another thing is that there are a lot of unanswered questions that we really need to work on. We need to do further work on antimicrobial resistance, because that is a big concern with this. So far, both our studies and all of the studies that have been done, have not shown a very clear signal of where the antimicrobial resistance might go, but it is definitely something to keep an eye on and look at further.

 

来源：《感染医线》

 

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