Antibiotics as STD Prophylaxis in Addition to PrEP?

At the virtual IDWeek 2020 conference, an interactive session titled “On the Cutting Edge of HIV Prevention” presented an online debate between Douglas Krakower, MD, of Beth Israel Deaconess Medical Center in Boston, and Annie Luetkemeyer, MD of the University of California San Francisco.

Luetkemeyer took the “pro” position on using doxycycline as chemoprophylaxis for PrEP users to reduce bacterial STI rates, while Krakower argued the “con” side — that this use of antibiotics was unnecessary. In this exclusive MedPage Today video, Krakower discusses the rationale both sides presented, and the takeaways from the debate.

Following is a transcript of his remarks:

I’m Doug Krakower, and I’m going to discuss a debate that we had about whether antibiotic prophylaxis should be given to people using HIV pre-exposure prophylaxis as a way to decrease rates of bacterial sexually transmitted infections in this population. And the debate was between me and Dr. Annie Luetkemeyer from UCSF, and Dr. Luetkemeyer took the “pro” position that we should be using doxycycline as chemoprophylaxis for PrEP users to try and reduce bacterial STI rates.

And the rationale for the pro side was that we know that rates of bacterial STIs are very high amongst people who are using PrEP in this country. And so behavioral strategies alone don’t seem to be working to decrease these rates. And Dr. Luetkemeyer appropriately pointed out that there are some important complications with all the STIs we’re seeing amongst PrEP users such as rare, but serious outcomes like ocular syphilis, leading to blindness in rare cases, there are increases in rates of congenital syphilis. And so all of these issues mean that we need to do more to try and reduce rates of STIs amongst PrEP users.

On the con side is that even though rates are quite high, it looks like we also probably are inflating rates of STI measurement amongst PrEP users by doing more screening than we ever have before. And so the argument against using STI prophylaxis is that we could generate more resistance and the resistance could be amongst bacterial STIs like gonorrhea, chlamydia, and syphilis, and also for other bugs out there that we use these antibiotics for.

So Dr. Luetkemeyer appropriately pointed out that there’s actually some data in support of using bacterial STI prophylaxis amongst PrEP users. There was a study in France called the Ipergay study, which looked at a randomized controlled trial of the 2-1-1 HIV PrEP regimen as compared to placebo. And in the Ipergay study, they actually had a substudy where they gave doxycycline 200 milligrams, times one as a post-exposure prophylaxis approach. So that people who were in the study, which was amongst MSM, were told to take a single dose of doxy right after they had sex. And the investigators track to see whether this decreased rates of incident STIs. And in this study, which is the only real major study looking at STI prophylaxis amongst PrEP users, it actually saw a pretty impressive decrease in rates of chlamydia and syphilis, but not gonorrhea. And those were the three major bugs that they track.

So Dr. Luetkemeyer appropriately pointed out, this would be really strong data to think about a broader set of trials, or even implementing doxy as PEP for PrEP users. But one of the things that’s important about this study is that even though doxycycline was safe, about 7% of people ended up stopping the medication due to gastrointestinal side effects from the doxycyclate.

And even though they didn’t find any problems with resistance to chlamydia in this study, they have very high rates of tetracycline resistance in gonorrhea that they found in this study. And so that’s probably the explanation for why doxy didn’t help rates of gonorrhea go down. And we know that amongst the major bacterial STIs, gonorrhea is probably the most important in terms of multi-drug resistant organisms out there.

So the punchline from the debate was that there’s some really good promising data that doxycycline has PEP could help decrease rates of chlamydia and syphilis amongst PrEP users, but probably not gonorrhea, given current rates of resistance to the tetracyclines, and on the con side, we really have to think hard about, will we be engendering more antibiotic resistance amongst gonorrhea and other pathogens out there, including syphilis, chlamydia, and others. Right now, there’s not a big problem with resistance to doxycycline amongst syphilis and chlamydia, but there are possibilities for this to emerge in the future. And so it needs to be watched closely.

Dr. Luetkemeyer and other groups are actually doing some very large randomized control trials with doxycycline as either PEP or even doxycycline PrEP amongst people using HIV PrEP or people living with HIV. And in the next few years, hopefully we’ll have really rich data to inform whether or not this works and what the potential unintended consequences are in terms of resistance, the effect on people’s microbiome from using antibiotic prophylaxis, and some of the important clinical outcomes. So it was a great debate and I hope that people will enjoy watching it. Thanks so much.