San Francisco's proactive rollout of doxycycline post-exposure prophylaxis (doxyPEP) has demonstrated a significant impact on reducing sexually transmitted infections (STIs) among high-risk populations. The intervention, involving a single 200mg dose of doxycycline taken within 72 hours after sex, has shown promising results in real-world settings, aligning with findings from recent clinical trials.
Real-World Impact in San Francisco
In October 2022, San Francisco became the first city to recommend doxyPEP for gay and bisexual men and transgender people. Data presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2024) revealed a steep decline in chlamydia cases and a reduction in syphilis cases following the implementation of doxyPEP. However, the decline in gonorrhea cases was less significant.
Dr. Hyman Scott reported early results from the San Francisco AIDS Foundation’s Magnet sexual health clinic, noting that among people who started doxyPEP, overall STI incidence fell from 18% to 8%, representing a 58% decrease. The decrease was more pronounced for chlamydia (67% drop) and early syphilis (78% drop) compared to gonorrhea (11% drop, not statistically significant).
Population-Level Analysis
Epidemiologist Madeline Sankaran and colleagues assessed the impact of doxyPEP at the population level, tracking STI incidence before and after the release of the city's guidance. The results showed a 7% monthly decline in chlamydia cases, resulting in a total decrease of 50% compared to predicted levels. Early syphilis cases also decreased by 3% per month, leading to a 51% drop. However, there was no significant change in gonorrhea cases. Sankaran noted that chlamydia cases among cisgender women rose during the same period, strengthening the conclusion that the decline among gay men and trans women is related to doxyPEP rollout.
Clinical Trial Evidence
These real-world findings are consistent with clinical trial results. Professor Jean-Michel Molina reported final results from the DoxyVAC trial, showing that doxycycline reduced the risk of chlamydia by 86% and syphilis by 79%, but gonorrhea by only 33%. Similarly, Professor Annie Luetkemeyer reported results from an open-label extension of the DoxyPEP trial, demonstrating sustained STI risk reduction among participants initially assigned to doxycycline.
Considerations and Limitations
While the results are promising, concerns remain regarding the potential for antimicrobial resistance with widespread doxycycline use. The dPEP Kenya trial also found that doxyPEP did not offer the same benefits for young cisgender women. Additionally, factors such as disruptions in STI screening due to COVID-19 and changes in sexual behavior in response to the 2022 mpox outbreak may have influenced the observed STI trends.
Despite these reservations, the proactive distribution of doxyPEP is emerging as a valuable tool in preventing STIs within communities. The San Francisco Department of Public Health's early adoption of doxyPEP guidelines has positioned the city as a leader in this area, with other cities and healthcare providers likely to consider similar strategies.
