Role of direct‐acting antivirals in people with HIV‐associated non‐Hodgkin lymphoma and concomitant infection: A study on behalf of the Fondazione Italiana Linfomi

: Chronic hepatitis C virus (HCV) infection is common among patients with human immunodeficiency virus (HIV)-related non-Hodgkin lymphoma (NHL). Although direct-acting antivirals (DAAs) achieve high sustained virological response (SVR) rates, data on their effects in people with HIV and HCV and affected by NHL remain limited. We conducted a retrospective study of 67 consecutive NHL patients with HIV and HCV (48 diffuse large B-cell lymphoma [DLBCL]) treated at 14 Italian centres (2010-2024). All patients received concomitant anti-retroviral therapy (ART). The median age was 51 years. The majority of patients were male (91%) and people who inject drugs (70%). Most patients (94%) received curative first-line immunochemotherapy (I-CT), mainly rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). After 2016, 26 patients received DAAs (8 concurrently, 18 after I-CT). DAA toxicity was minimal, and SVR was achieved in all cases. With a median follow-up of 91 months, the 3-year overall survival (OS) was 61%. Patients treated with DAAs had better 5-year OS (81% vs. 48%, p = 0.035), with no difference between those who received DAAs subsequently or concurrently with I-CT. Multivariate analysis identified high age-adjusted International Prognostic Index (aaIPI), HIV score 3-6, female sex and absence of rituximab treatment as independent risk factors for OS, while DAAs had a borderline impact (p = 0.055). In conclusion, DAA therapy during or after I-CT is feasible, safe and highly effective in this high-risk group.