Background: Current available treatments (benznidazole and nifurtimox) for Chagas disease (CD) show limited efficacy in chronic phase and frequent undesirable effects. Ergosterol synthesis inhibitors (ESI) had been considered as promising drugs for CD treatment and despite its recent poor results in several clinical trials, different strategies have been proposed to optimize its role in this infection. Case presentation: We present a case of chronic Chagas disease in patient diagnosed with HIV who received treatment for histoplasmosis with itraconazol during twelve months. Even though T. cruzi rt-PCR was persistently negative during treatment, when itraconazol was stopped she presented with a positive blood rt-PCR. Conclusion: Several studies using different ESI had been published for CD treatment. Either in vitro or in vivo assays demonstrated activity against T. cruzi of the different triazole derivatives so different clinical trials had been carried out to evaluate its efficacy and safety. Despite contradictory evidence in the animal model, longer treatments along with other treatment strategies previously proposed suggests that ESI failure rates in positive peripheral blood rt-PCR are higher than that obtained with the current treatments of choice.