Syphilis and Mpox in Sexual and Gender Minority Populations: Screening, PrEP, and DoxyPEP

Conclusions

• Syphilis remains highly prevalent in sexual and gender minority populations, especially men who have sex with men and people with HIV, and can be clinically aggressive or atypical in these groups.
• Syphilis lesions can closely mimic mpox and other STI-related skin findings, so diagnosis should rely on testing rather than appearance alone.
• Receptive anal exposure is associated with more secondary syphilis presentations, likely because perianal primary lesions are easier to miss and diagnosis is delayed.
• Transgender people may also have substantial STI burden, but risk varies widely by sexual behavior and is poorly captured because gender minority data are inconsistently collected.
• Routine syphilis screening should be more frequent in sexually active MSM and in people with HIV, with screening intervals tailored to risk and local epidemiology.
• Doxycycline prophylaxis, both pre-exposure and post-exposure, can substantially reduce syphilis and other bacterial STI incidence in studied MSM and transgender women populations.
• Evidence for doxycycline prophylaxis is weaker or absent in some other groups, such as cisgender women, so findings cannot simply be generalized to all populations.
• Despite concerns about risk compensation, studies generally did not show major changes in sexual behavior after doxycycline prophylaxis, but antibiotic resistance remains an important concern.
• Widespread use of doxy-PEP may be associated with declining syphilis trends in places like San Francisco, although population-level causality is not fully certain.
• Doxycycline prophylaxis can cause adverse effects such as fixed drug eruptions, which should be recognized in patients using it.