Refining Trichomonas vaginalis treatment in women and men.

Abstract Trichomonas vaginalis is estimated to be the most common non-viral sexually transmitted infection (STI). It causes considerable and costly perinatal/reproductive morbidity, disproportionately affects persons of color, and can amplify HIV transmission. After our two trials found multi-dose oral metronidazole (MTZ) to be superior

to single-dose 2 g oral MTZ, the Centers for Disease Control and Prevention now recommends multi-dose MTZ as the treatment of choice for T. vaginalis in all women. Since neither trial included men and there is a paucity of data in men, single-dose 2 g oral MTZ stands as the recommended treatment for men. In both

female trials, however, even though multi-dose oral MTZ was found to be superior to single-dose MTZ, multi- dose MTZ still had unacceptably high rates of breakthrough infection (9%-11%). With approximately 2.6 million cases of T. vaginalis per year in the United States, over 280,000 persons/year are estimated to be insufficiently

treated with multi-dose oral MTZ. Thus, there is a critical need to refine T. vaginalis treatment. Single-dose 2 g oral secnidazole (SEC), a next generation 5-nitroimidazole, may be a good option. Our recent trial found that single-dose 2 g oral SEC was superior to placebo in T. vaginalis-infected women. Oral SEC has multiple

benefits compared to multi-dose oral MTZ including a longer half-life and improved tolerability. Single-dose SEC poses less burden on the patient and can treat bacterial vaginosis, a common comorbidity among women with T. vaginalis. On the other hand, MTZ is far less costly and can be given during pregnancy/lactation. The

overall goals of this multi-centered, randomized trial are to examine the effectiveness and cost-effectiveness of oral multi-dose MTZ compared to single-dose oral SEC inboth women and men with T. vaginalis. Aim 1. To examine the optimal treatment for T. vaginalis infection in women and men. This will be done by

conducting an open-label, randomized, multi-centered, parallel phase IV clinical trial comparing oral multi-dose MTZ (500 mg BID for 7 days) to single-dose oral 2 g SEC for the treatment of T. vaginalis in women and men. The test-of-cure (TOC) visit will be 4 weeks (± 1 week) after completion of treatment. We hypothesize that T.

vaginalis repeat infection rates at TOC will be 1.75 lower in the single-dose 2 g oral SEC arm versus the multi- dose oral MTZ arm. Aim 2 To compare the cost effectiveness of multi-dose oral MTZ versus single-dose oral SEC for the treatment of T. vaginalis infection. We will compare the direct and indirect costs of

treatment using either arm, taking into consideration the reproductive and perinatal outcomes associated with T. vaginalis infection as well as increased risk for HIV-acquisition. We hypothesize the single-dose SEC will have higher initial cost but will be more cost effective compared to multi-dose MTZ, largely due to lower

breakthrough rates. Data from these aims will fill critical gaps in the literature and provide data on refining the treatment of T. vaginalis among women and men, with the long-term goal of reducing health disparities attributable to this common infection.