Doxycycline pre-exposure prophylaxis (doxyPrEP) is a promising strategy for preventing bacterial sexually transmitted infections (STIs) among men who have sex with men (MSN) as well as women, suggest two studies presented at AIDS 2024.

“Taking doxycycline after condomless sex can significantly reduce the risk for a number of bacterial STIs in some populations, and this intervention is called doxyPEP, or doxycycline post-exposure prophylaxis,” said Sharon Lewin, MD, PhD, the president of the International AIDS Society, and the international co-chair of AIDS 2024, who moderated a press briefing at the conference.

“But there has been less attention to another approach—something called doxyPrEP, or doxycycline pre-exposure prophylaxis—which involves taking doxycycline before sex to prevent STIs,” added Dr. Lewin, who is also the director of the Peter Doherty Institute for Infection and Immunity at the University of Melbourne, in Australia. Although the two new studies were small, she called them “intriguing.”

A randomized controlled pilot study enrolled 52 MSM with HIV and a history of syphilis in British Columbia (abstract 11987). They were randomly selected to receive 100 mg of doxycycline daily or placebo and followed for 48 weeks.

“We were primarily focused on feasibility as our primary outcome,” said Troy Grennan, MD, of the British Columbia Centre for Disease Control. “Our secondary outcomes were STI incidence, antimicrobial resistance and changes in sexual behavior.”

Forty-one participants (79%) completed the study. The researchers used several measures for adherence, including counting pills, and found more than 85% of the participants were adherent. The team reported reductions in syphilis, chlamydia and gonorrhea of, respectively, 79%, 92% and 68% in the doxyPrEP arm compared with the placebo group.

“Overall, doxyPrEP led to an 80% reduction in any of the three STIs we were looking at,” he said.

However, there is concern about resistance developing. New doxycycline resistance developed in three Staphylococcus aureus isolates in the doxycycline arm and two isolates in the placebo group.

“The study … really does support, I think, the ongoing investigation of doxyPrEP as an intervention for STI prevention,” he said.

Dr. Grennan and his colleagues are recruiting more than 550 participants into a larger trial comparing the effectiveness of doxyPrEP and doxyPEP. He also wants to see STI prevention research move forward equitably, dedicating more effort toward key populations that haven’t received as much attention, such as cisgender women and young people.

The second doxyPrEP study enrolled 40 female sex workers in Tokyo; most were in their 20s and were Japanese. The women were each provided with 100 mg of doxycycline daily and followed over time (abstract 7947).

After initiating doxyPrEP, the overall STI incidence rate declined from 232.3 to 79.2 per 100 person-years. Syphilis incidence was reduced to zero, there was a marginally significant reduction in chlamydia, but there was no significant change in gonorrhea, according to Seitaro Abe, MD, of the National Center for Global Health and Medicine, in Japan.

Follow-up interviews revealed high adherence to and satisfaction with the doxyPrEP regimen. In fact, 72.7% of respondents indicated using doxyPrEP reduced their fear of STI transmission. In addition, the women said they visited a health clinic more often after starting the study.

No serious adverse events were reported, but 22.7% of the respondents reported nausea and vomiting after taking doxycycline.

The findings support the introduction of doxyPrEP to highly vulnerable populations, he said.