Syphilis remains an important cause of morbidity in gay, bisexual, and other men who have sex with men (gbMSM). Up to 75% of early syphilis infections occur in gbMSM– a population with syphilis rates nearly 10-fold higher than in those who are HIV negative. In Canada’s urban centres, 2/3 of syphilis cases are in HIV-positive gbMSM, and re-infection remains high. HIV co-infection with syphilis has important implications for HIV management. Syphilis may increase HIV viral load levels in virologically suppressed individuals , and genital ulcers increase the risk of HIV transmission and acquisition.

Significant advancements have shaped the past two decades of HIV care. Antiretroviral therapy (ART) has substantially reduced HIV-associated morbidity and mortality and extended life expectancy to near-normal levels. Further, new evidence has emerged demonstrating the efficacy of HIV PrEP in preventing HIV acquisition. The combination use of tenofovir/emtricitabine was shown in the iPREX trial to reduce the risk of HIV acquisition by 44% in HIV-negative gbMSM when taken daily as PrEP. Among those with detectable drug levels, the risk reduction was > 90%.The exciting developments in HIV prevention have encouraged investigators to expand this strategy to the prevention of other STIs, a modality previously shown to be acceptable to gbMSM. Given the paucity of data on the use of doxycycline as syphilis PrEP, the primary issue to be addressed in a pilot study would be the feasibility of daily doxycycline. Feasibility would entail an assessment of adherence to the medication, as well as its tolerability (i.e. side effect profile, and side effect-related discontinuations).

This will be a prospective, double-blind, randomized controlled multi-centre pilot trial of daily doxycycline versus placebo for the prevention of incident syphilis cases among high-risk HIV positive gbMSM over 15 months of follow-up. Of note, participants will receive the intervention for a total of 12 months; the month 15 visit is to allow for sufficient follow up time to ascertain for any infections during the window period that may have gone undiagnosed at month 12.