Long-term follow-up of individuals with Chagas disease treated with posaconazole and benznidazole in a non-endemic region: the CHAGASAZOL cohort

Abstract

Objectives: The CHAGASAZOL trial compared posaconazole and benznidazole for treating chronic Chagas disease. Posaconazole showed poor short-term efficacy by means of real-time polymearse chain reaction (qPCR) compared with benznidazole, but few studies have reported long-term follow-up using this tool. The aim of this study was to provide a more comprehensive analysis of the CHAGASAZOL cohort through 11 years of follow-up.

Methods: This is a prospective observational cohort of individuals who were included in the CHAGASAZOL trial. Data were censored as of 31 December 2023. Subjects initially treated with posaconazole with a positive qPCR were offered re-treatment with benznidazole. All patients underwent clinical and electrocardiographic evaluations as well as a qPCR at a 6-month or 1-year interval. The primary objective was parasitological failure, defined as any positive qPCR in peripheral blood at any time during follow-up.

Results: Seventy-two participants were enrolled (median follow-up: 71 months, range 1-147 months). At baseline, 59 (82%) were classified as indeterminate forms, 9 (12%) as cardiac, 2 (3%) as digestive, and 2 (3%) as mixed forms. Forty-eight participants received posaconazole, 45 completing at least 1 follow-up visit. Up to 43 of 45 (95%) presented a positive qPCR, and of them, 35 accepted to be retreated with benznidazole. Considering those treated with benznidazole (either initially or as a re-treatment), only 3 of 51 (6%) showed a positive qPCR. Four (5.5%) participants showed cardiac progression after 3-10 years of follow-up, with an incident rate of 0.94 events per 100 person-years. Two of them had received the complete benznidazole treatment, 1 was partially treated (17 days) and 1 was only treated with posaconazole before clinical progression.

Discussion: Even if benznidazole showed parasitological efficacy, lifelong follow-up should be offered to individuals living with Chagas disease, as both parasitological failure and clinical progression can occur many years after diagnosis and treatment.

Keywords: Benznidazole; Chagas; Chagas disease; Non-endemic cohort; Posaconazole.