Stopping HIV and STIs in a New Era of Care

Elizabeth Millard

July 21, 2023

A growing body of research suggests that the antibiotic doxycycline can lower the risk of contracting some sexually transmitted infections (STIs), including gonorrhea, chlamydia, and syphilis — the three most common bacterial STIs — if taken within a few hours to days after sex.

The postexposure prescriptions, which are called doxy-PEP, are also being offered to patients with HIV to reduce their risk of contracting other infections.

But in a world increasingly concentrated on reducing antibiotic prescriptions to curb resistance, the notion of antibiotic add-ons for prevention is controversial and will be the topic of clinical debate in an upcoming session at the International AIDS Society Conference on HIV Science (IAS) on Tuesday, July 25, in Brisbane, Australia.

Jean-Michel Molina, MD, PhD, professor of infectious diseases at the University of Paris and head of the infectious diseases department at the Saint-Louis and Lariboisière Hospitals in Paris, will take the podium at the meeting to help weigh the pros and cons of the approach.

Molina's primary clinical research focuses on HIV infection, and he chairs a clinical trial group for the French National Agency for AIDS Research. As part of a discussion summarizing new evidence for prevention and treatment of HIV and STIs, Molina plans to highlight the short-term benefits of doxycycline.

And he will also address the concerns that must be navigated before this approach can be considered a standard of care.

The only current recommendation for prophylactic use of doxycycline is for malaria, according to a National Library of Medicine report, although the drug is also used to prevent anthrax when it is suspected to be present in a bioterror attack.

In a study published in The New England Journal of Medicine earlier this year, doxy-PEP was tested in a population of people having sex without a condom.

The Promise of Doxy-PEP

In the research, those who took doxycycline had a 65% overall reduction in new STIs with a dosage used within 24 to 72 hours after sex.

The study involved only men who have sex with men who were either HIV positive or were taking HIV prevention medication. The research showed that doxy-PEP reduced new cases of chlamydia by about 80% and gonorrhea by more than 50%.

The results were so notable that the researchers stopped the trial earlier than planned so participants in the control group could also receive doxy-PEP to gain similar benefits.

The research team led by Annie Luetkemeyer, PhD, professor of medicine and infectious diseases at the University of California, San Francisco, pointed out at the time that doxy-PEP was well tolerated by the participants, who were already at an elevated risk of STIs.

These results are similar to another study on doxy-PEP, led by Molina and published in The Lancet in 2017. In that research, also conducted with men who have sex with men, doxy-PEP reduced the occurrence of a first episode of bacterial STIs by about 70% among participants.

On the basis of results like these, and particularly NIH clinical trial data presented at the 2022 IAS conference, the Centers for Disease Control and Prevention (CDC) announced it would be developing clinical guidance on the safe and effective use of doxy-PEP for bacterial STI prevention among gay and bisexual men and transgender women.

A follow-up statement issued earlier this year by Leando Mena, MD, director of the CDC's Division of STD Prevention, noted that the momentum in research exploring STI prevention is encouraging, particularly because the field has lacked innovation for some time.

Mena added that there are still many gaps left to fill and research to be done, including confirmation of the benefits for widespread use of doxy-PEP.

In the IAS session, the main concern that Molina plans to cover with doxycycline use is antimicrobial resistance.

Prescribing Pitfalls

Preliminary research results presented at the 2023 CROI conference by UC San Francisco, the San Francisco Department of Public Health, and the University of Washington showed that this type of resistance appears to be modest but that more work needs to be done to understand the extent and trajectory of antimicrobial resistance associated with intermittent doxycycline use.

For example, Molina will be talking about the uncertainty of the effects of regular use of doxy-PEP as opposed to a one-time use that would likely not raise resistance issues.

However, that's not the only potential downside. In putting together its doxy-PEP guidelines, the CDC issued a series of considerations that should be used to inform healthcare decisions.

The drawbacks they highlighted include the fact that efficacy data only apply to gay and bisexual men and transgender women, since studies among heterosexual cis-gender women are ongoing.

Another issue is the potentially adverse side effects of doxycycline in addition to resistance. Most notably, the CDC reported, the antibiotic can cause phototoxicity, gastrointestinal symptoms, and more rarely, esophageal ulceration.

Questions regarding frequent and long-term use of doxy-PEP are likely to drive not just the IAS discussion but also recommendations from the CDC and other health guidance providers for the foreseeable future.

International AIDS Society (IAS) 2023 Conference on HIV Science.

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