NS3 protease inhibitors are set to improve sustained virological response rates in HIV-positive patients with hepatitis C. We measured the prevalence of natural resistance polymorphisms in 38 acutely infected treatment-naive patients using direct and deep sequencing. Twenty six percent of patients (10/38) had a majority variant resistance mutation (in order of frequency; Q80K - 16%, V36M - 5%, T54S - 3%, V55A - 3%, and D168A - 3%). Low-frequency mutations were detected in all samples. Further studies are required to determine threshold levels associated with treatment failure.