The invention relates to an in vitro method for determining in an isolated sample of a subject the presence of one or more Human Hepatitis C Virus (HCV) sequence variants comprising reverse transcription and amplifying HCV RNAs molecules using specific sets of primers allowing the amplification of the HCV regions named 5′-UTR-Core and NS5B. The method includes an step for purifying the amplified regions and a sequencing step of the amplified fragments. The invention also includes specific oligonucleotides than are used as primers in the method, as well as kits including one or more of these oligonucleotides as sets of primers.