Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection (STI) in the world, with an estimated 232 million incident infections in 2019. Prior to 2021, the Centers for Disease Control and Prevention (CDC) Sexually Transmitted Infection (STI) Treatment Guidelines recommended either doxycycline (100 mg twice daily for 7 days) or azithromycin (1 gram single dose) for the treatment of both rectal and urogenital CT. The 2021 revised guidelines recommend doxycycline as the preferred treatment for CT, except for pregnant women and persons for whom adherence with multiday dosing is a considerable concern. The 2021 World Health Organization (WHO) Guidelines for symptomatic STI treatment also recommend a seven-day regimen of doxycycline for CT treatment. The extent to which this recommendation will be translated into practice remains to be seen, since many clinicians prefer to use azithromycin due to the relative ease of a single dose treatment and possibility for directly observed therapy in some settings. Clinicians have raised concerns about incomplete patient adherence to a week-long regimen, particularly in adolescents.~One impetus for changing the CT treatment guidelines was the available evidence that doxycycline is substantially superior for treatment of rectal CT compared to azithromycin. Rectal CT is well-recognized as a common infection among cisgender men who have sex with men (MSM) and other persons assigned male at birth (AMAB) but is often overlooked among cisgender women and other persons assigned female at birth (AFAB). Increasing evidence demonstrates that rectal CT is common and may impact treatment success for concomitant urogenital infections among women. Among cisgender women, the prevalence of rectal CT among clinic patients is 8-9%, and approximately 70% of women with urogenital CT have concurrent rectal CT. However, routine screening for rectal CT is not recommended for cisgender women because the clinical implications of this infection are uncertain. Undiagnosed and inadequately treated rectal infections may lead to infections or re-infections in the urogenital tract, but there is insufficient evidence for that hypothesis to date. To the extent that women are treated with azithromycin rather than doxycycline due to adherence concerns, unrecognized and inadequately treated rectal infections may contribute to urogenital re-infection and adverse reproductive health outcomes.~The full 7-day regimen of doxycycline may not be required to cure CT infection. Clinical trials using less frequent doxycycline regimens or higher initial doses of doxycycline have demonstrated cure rates of 98%, and observational evidence suggests that partial adherence to the 7-day regimen is sufficient to achieve clinical cure.~This study will examine the non-inferiority of a 3-day regimen of doxycycline compared to the recommended 7-day regimen for the treatment of both rectal and urogenital CT. If this shorter regimen is found to be non-inferior to the standard 7-day regimen, it is anticipated that uptake of doxycycline for CT treatment will become more widespread, leading to better individual and public health outcomes compared to widespread use of azithromycin, and at a lower cost with more judicious antibiotic use than a 7-day doxycycline regimen.
Participants will take a 3-day course of doxycycline or a 7-day course of doxycycline to treat urogenital chlamydia infections (women) and rectal infections (men).