The Impacts of Antiretroviral and Antifungal Treatments, and Tuberculosis Co-infection on Mortality and Relapse in Patients with Talaromyces Marneffei Infection

Abstract

To date, clinical data on long-term clinical outcomes, including 6-month mortality and relapse in talaromycosis (Tm) patients and impacts of ART and secondary antifungal prophylaxis are still lacking. We conducted a secondary data analysis from 6-month prospective observation of patients with culture-confirmed talaromycosis who participated in the Itraconazole versus Amphotericin B for HIV-associated Talaromycosis (IVAP) trial. The primary outcome was 6-month Tm mortality, while the secondary outcome was relapse. Multivariable Cox proportional hazard models were used to identify predictors of outcomes of interest. The median patient age was 34 years (IQR:30 – 38). The median pre-ART CD4 counts at baseline were 10 (IQR: 5-21) cells/µL. The cumulative 76/435 (17.4%) patients died, and Tm relapse was observed in 18/435 (4.1%) patients. The multivariable analyses showed that strong independent predictors of 6-month Tm mortality included ineffective ART (either absence of ART or ART failure) (HR = 6.26, 95% CI: 3.95 – 9.92, P < 0.001), and TB co-infection (HR =1.98, 95% CI: 1.23 – 3.17; P < 0.01). Induction antifungal treatment with itraconazole versus amphotericin B deoxycholate was significantly associated with Tm death in the univariable model, however, it became insignificant in the multivariable model. In addition, the significant risk factors for Tm relapse were ineffective ART, induction antifungal treatment with itraconazole than intravenous amphotericin B, and shorter duration of itraconazole secondary prophylaxis after completing induction therapy in-hospital (all with significant P-values). Antiretroviral therapy, antifungal treatment and tuberculosis co-infection were main predictors for 6-month Tm fatality as well as relapse. Keywords: Invasive fungal infections, Mortality, Relapse, Talaromyces marneffei, Vietnam.