To understand how awareness of HIV-positivity and the use of antiretroviral therapy associated with syphilis infection, 361 MSM attending 16 Hong-Pa (drug-and-sex parties) in Taiwan were studied. The syphilis rate of individuals within their first 2 years after HIV diagnosis (awareness) was lower than that in individuals who had not been diagnosed HIV infection prior to Hong-Pa (unawareness) (Adj OR = 0.24, P < 0.05). Notably, there was a decrease in the beneficial effect of HIV-positive status awareness on syphilis prevention with an increase in time since notification. Moreover, antiretroviral therapy was not associated with a lower incidence of syphilis, and syphilis infection peaked during the treatment dropout period. In conclusion, the duration of a protective effect of knowing one's HIV-positivity against syphilis infection was short, and the highest risk of syphilis infection was observed when patients discontinued antiretroviral therapy. Future research should examine the behavioral mechanisms involved in this prevention failure.