The transmission of direct-acting antiviral (DAA) resistance-associated substitutions (RAS) may inhibit hepatitis C virus (HCV) cure rates and elimination efforts, according to research presented at the virtual Conference on Retroviruses and Opportunistic Infections, held March 8 to 11, 2020.

Investigators from the Netherlands analyzed a population of men who have sex with men (MSM), who were living with HIV, were diagnosed with a recently acquired HCV genotype 1a infection, and participated in 2 trials studying the effectiveness of DAA therapy. The study included a total of 87 participants with completed plasma samples. RAS were defined based on the European Association for the Study of the Liver guidelines, whereas clusters were defined as a bootstrap support value of >90% and a genetic threshold <3%. Maximum likelihood analysis was performed on a concatenated NS5A+ BS5B alignment.

Whole-genome sequencing analysis identified 6 clusters containing 82 of 87 recently acquired HCV infections, and 4 of the clusters included ≥10 MSM. Importantly, the clusters continued to be present and of a similar size even after widespread treatment with DAA. Additionally, a single large cluster demonstrated that 96% of recently acquired HCV infections harbored the NS5A M28V RAS at baseline. Patients in this cluster also presented with several other RAS including E62A, H58P and Y93H.

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These results demonstrated that larger clusters were detected in the years before and after DAA introduction regardless of prevention measurements, suggesting ongoing transmission. The researchers recommended ongoing resistance surveillance to detect the transmission of other RAS and targeted prevention measurements for this highly clustered epidemic.


Popping S, Verwijs R, Cuypers L, Claassen M, van den Berk G, De Weddheleires A, et al. Transmission of the NS5A resistant variant M28V among acute HIV/HCV co-infected MSM.  Presented at: CROI 2020. March 8-11, 2020. Accessed March 19, 2019.