A Randomized, Placebo-controlled Trial of Oral Doxycycline for the Prevention of Syphilis in HIV-positive Men Who Have Sex with Men (MSM)

Syphilis disproportionately impacts gbMSM:

Syphilis remains an important cause of morbidity in 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.

The era of novel, biomedical prevention technologies:

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. With reduced morbidity and mortality associated with HIV, gbMSM may also be changing their sexual behaviours. Seroadaptive strategies, such as serosorting (selecting sexual partners of the same serostatus) and seropositioning (selecting a sexual position to minimize the risk of HIV transmission) are common among gbMSM. While this may be mitigating the risk of HIV transmission or acquisition, there is evidence to suggest that decreasing condom use may contribute to a rise in syphilis and other bacterial STIs in high-risk populations. 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 Pre-exposure Prophylaxis Initiative (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%.

A role for PrEP in other STIs? 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. A recent pilot study randomized participants to receive either the antimicrobial doxycycline daily or a monetary incentive to remain STI-free throughout the study period. After 48 weeks, those receiving doxycycline were significantly less likely to be diagnosed with any STI (odds ratio: 0.27; 95% confidence interval: 0.09-0.83). Though there was also a trend toward benefit for doxycycline in specifically preventing syphilis, significance was not achieved for this outcome.