Editor's Note: At the 25th International AIDS Conference, a study led by Dr. Troy Grennan from the British Columbia University and the Canadian Centre for Disease Control revealed the astonishing effectiveness of doxycycline pre-exposure prophylaxis (DoxyPrEP) in reducing the incidence of bacterial sexually transmitted infections (STIs) among HIV-positive men who have sex with men. The study found that taking 100 mg of doxycycline daily significantly reduced the incidence of syphilis, chlamydia infection, and gonorrhea, with an overall reduction rate of up to 80%. This breakthrough discovery not only provides a new strategy for STI prevention but also offers important evidence for future public health policy formulation. With the advancement of larger-scale clinical trials, doxycycline is expected to become an important tool in the field of STI prevention, contributing to global public health security. " Infectious Disease Frontier"（IIDF） invited Dr. Troy Grennan for an exclusive interview.01
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.
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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.
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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.
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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.
