On the basis of remarkable antitumor activity, programmed death receptor-1 (PD-1) inhibitors pembrolizumab and nivolumab were\napproved for the treatment of advanced melanoma in the second-line setting following progression on either CTLA-4 inhibitor\nipilimumab or BRAF/MEK inhibitors (for BRAF mutated melanoma). Given hypothesized risk of triggering exacerbations of\nautoimmune diseases and/or chronic viral infections, clinical trials (including regulatory studies) evaluating checkpoint blocking\nantibodies PD-1 and CTLA-4 have excluded patients with autoimmune diseases, chronic hepatitis B/C virus (HBV/HCV), and/or\nhuman immunodeficiency virus (HIV) infections. Herein, we describe two patients with advanced melanoma and concomitant\nHCV/HIV infections treated with PD-1 inhibitor pembrolizumab. Patient 2 with HIV/HCV coinfection progressed after 2 doses\nof pembrolizumab. Patient 1 who had HCV alone was treated with pembrolizumab with initial partial response. HCV viral load\nremained stable after 9 cycles of pembrolizumab following which 12-week course of HCV-directed therapy was commenced,\nresulting in prompt reduction of HCV viral load below detectable levels. Response is ongoing and HCV viral load remains\nundetectable. In both patients, no significant toxicities were observed when pembrolizumab was initiated.We argue for the further\ninvestigation of checkpoint inhibition in cancer patients with underlying chronic viral infections in the context of carefully designed\nclinical trials.
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