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Purpose: Data on the frequency of HCV naturally occurring drug-resistant variants (RAVs) at baseline in HIV/HCV coinfected patients are scarce. Methods: NS3-HCV RAVs were studied by full-population direct sequencing from plasma specimens of 345 DAA-naïve patients with HCV chronic hepatitis (159 of them with HIV/HCV-coinfection). Results: NS3 RAVs were identified in 31.5 % of patients, with a significant proportion of HIV/HCV coinfected DAA-naïve patients compared to those with HCV monoinfection (38 vs. 25 % p = 0.0104, OR 1.84; 95 % CI 1.162-2.916). Conclusions: HCV resistance genotyping test before treatment may be worth in special populations such as HIV/HCV coinfection to optimize patient treatment. [ABSTRACT FROM AUTHOR]