As 2019 draws to a close, TheBodyPro takes stock of the year's most noteworthy developments in HIV. And not just any developments: We're looking specifically at those with the largest impact for people who provide HIV care and services in the U.S. In this series, veteran clinician-researcher David Alain Wohl, M.D., guides us through the new research and other important moments of 2019 that have the greatest potential to alter the HIV clinical landscape in the months and years to come.
I messaged Craig through the patient portal of our electronic medical record using the subject line, "Your Labs." He would know immediately what that meant: His sexually transmitted infection (STI) test came back with something positive.
Craig has sex with men and has been living with well-controlled HIV infection for over 15 years. Ever since we started doing basic STI risk assessment and self-swabbing in our clinic, he has regularly had one or more positive results. This time, his RPR was 1:256 -- and this occurred after he had syphilis diagnosed about 18 months ago, which responded appropriately to intramuscular penicillin.
Craig came in and, after his shot, asked if there was anything he could do -- other than condoms -- to prevent some of these STIs. He does not use illicit drugs or alcohol, does use condoms most of time when he is a bottom, and is vaccinated against hepatitis A and hepatitis B. He said he heard that maybe taking an antibiotic could prevent syphilis. "Should I be on that?"
Rates of bacterial STIs in the U.S. have been climbing, especially for men who have sex with men (MSM). This trend pre-dates HIV pre-exposure prophylaxis (PrEP), but as PrEP uptake has increased -- perhaps leading to more screenings for gonorrhea, chlamydia, and syphilis -- numbers have risen even more sharply. While we now have PrEP and post-exposure prophylaxis (PEP) as biomedical interventions for HIV, the same cannot be said for bacterial STIs, despite their being around much longer and being considerably more prevalent.
Doxycycline has been toyed with as a potential STI prophylaxis. It is relatively well-tolerated, and it is already regularly taken for a variety of purposes, from acne to malaria prophylaxis. It has activity against chlamydia and syphilis, albeit not gonorrhea.
At CROI 2017, the French ANRS research group first presented intriguing results from a trial conducted among 232 MSM and transgender women who were enrolled in the IPERGAY study, which explored intermittent PrEP dosing. Of the people who were randomized to take 200 mg of doxycycline within 24 to 72 hours of condomless sex, there were significantly lower rates -- roughly 70% less -- of both chlamydia and syphilis compared to the half of participants who were not assigned the antibiotic. (As expected, there was minimal impact of doxycycline use on gonorrhea incidence.) Adherence was decent, with 83% of participants reporting use of doxycycline and about 60% having levels detected in plasma. Gastrointestinal adverse effects led a handful to stop the medication.
That was in 2017. So, why bring this up now?
Since the ANRS study, STI rates have continued to head north. However, there has been little progress on their prevention -- and limited additional study of a potential role for doxycycline.
This year, however, an international team of experts conducted a thoughtful review of prior research regarding the use of doxycycline for STI prevention. In their analysis of the data -- which included the ANRS study, a much smaller earlier clinical trial, and a modeling study of the drug's impact in Australian MSM -- the authors state that doxycycline for STI prevention shows promise.
At the same time, they urged caution regarding the unknowns about doxycycline use, such as the development of drug resistance (which is arguably less an issue for syphilis, chlamydia, and gonorrhea than it is for other common staphylococcal and streptococcal pathogens) and the drug's effect on a patient's microbiome. In addition, identification of the populations most likely to benefit from doxycycline was considered a priority.
The Bottom Line on Doxycycline for STI Prophylaxis
As an infectious diseases specialist, I get why chronic usage of antibiotics can be problematic. The dysbiosis of the gut and other flora alone gives one pause. However, I am also aware that we prescribe antibiotics all the time, whether it is for prophylaxis of opportunistic infections in immunocompromised people (e.g., those with advanced HIV infection, transplant recipients, people on chronic immunosuppressant therapy) or less dangerous situations such as acne.
For those at a high risk for STI infection, exposure to antibiotics should already be a concern: Repeated injections of penicillin, along with empiric antibiotics to cover potential infection with gonorrhea and chlamydia, can add up. Craig has certainly seen his fair share of antibiotics for treatment of his STI; would post-coital doxycycline be worse?
Yes, antibiotic drug resistance is a real concern. In the review paper, the expert authors point out that for gonorrhea, that train has already left the station: Data showed high levels of already-present resistance to tetracyclines, precluding use of these agents. For chlamydia, less is understood about drug resistance, or about the correlation between resistance test results and likelihood of clinical response. More of a concern is that periodic doxycycline could shift susceptibility of Mycoplasma genitalium, a common cause of non-gonococcal urethritis in men, as well as among commensal organisms, including those that can cause disease.
In sum, there are risks and there are benefits. For Craig, whose butt was starting to smart from the depot of antibiotic he was sitting on, the latter outweighed the former: He left with a prescription for doxycycline, detailed written instructions on how to use it, and recommendations for a good sunscreen in case it causes photosensitivity.