Phylogenetic Analysis May Assist With HCV Prevention Strategies in PWID

Next-generation sequencing is an important tool that can help differentiate HCV reinfection from treatment failure, and may assist with the design of targeted prevention strategies in PWID receiving opioid agonist therapy.

Next-generation sequencing is an important tool that can help differentiate hepatitis C virus (HCV) reinfection from treatment failure, and may assist with the design of targeted prevention strategies in people who inject drugs (PWID) receiving opioid agonist therapy, according to study results published in the Journal of Infectious Diseases.

Researchers used data from the PREVAIL study, including an extension study, to analyze baseline and follow-up specimens from 150 PWID from 3 opioid treatment programs in the Bronx, New York. To examine whether there were any transmission linkages among the participants, researchers used GHOST, a cloud-based technology that uses next-generation sequencing amplicon data of viral hepatitis target genes to analyze and visualize transmission clusters in an independent, accurate, and reproducible way.

Of the 150 participants, 75% reported a history of injection drug use. Injection drug use was reported in the 30 days before HCV treatment in 52% of participants (n=59), 49% of participants at 12 weeks post-treatment (n=55), 47% of participants at 24 weeks post-treatment (n=53), and 19% of participants (n=22) in the extension study cohort. A majority were infected with HCV genotype 1a (n=128), and the remaining with genotype 1b (n=22).

At baseline, there were 2 pairs of participants who were linked by transmission. Both pairs of participants attended the same opioid treatment programs and were involved in spousal or common-law partnerships. “This finding has important implications for counseling PWID regarding the risk of transmission to their partners, providing sterile injecting equipment to these individuals, and, perhaps, prioritizing treatment of such pairs to prevent HCV reinfection following treatment of one infected partner,” noted the researchers.

Nine participants did not achieve sustained virologic response, with 2 dying while receiving HCV treatment. The 7 participants remaining had similar sequences at baseline and post-treatment consistent with treatment failure.

Four participants were viremic after treatment and evidence of sustained virologic response. Phylogenetic data suggested new infections with HCV genotype 1a and 3a strains in 1 of these participants. Another participant was only transiently viremic 17 months post-treatment, with no specimen sent for next-generation sequencing. The other 2 participants both had a very heterogeneous genotype 1a viral population at baseline, suggesting infection with more than 1 HCV strain; both individuals demonstrated sustained virologic response with treatment, but experienced HCV reinfection with a genetically distant HCV strain at week 24 post-treatment, and this new viral population expanded in the extended 12-month follow-up. “Emergence of HCV population genetically distant from baseline, which is seemingly resistant to the treatment, opens opportunity for misclassification of late treatment failure as reinfection, potentially misleading retreatment decisions,” stated the researchers.

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Three participants who experienced viremia post-treatment reported ongoing high-risk behaviors, which is supportive of reinfections in these participants and they should be considered for targeted intervention and harm reduction, added the researchers.

“If these high-risk networks can be identified [in PWID], harm reduction and HCV treatment services can be delivered to these groups, which will be critical for HCV elimination efforts,” concluded the researchers.

Disclosure: Matthew J. Akiyama, MD, and Alain H. Litwin, MD declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of their disclosures.


Akiyama MJ, Lipsey D, Ganova-Raeva L, et al. A phylogenetic analysis of HCV transmission, relapse, and reinfection among people who inject drugs receiving opioid agonist therapy [published online March 9, 2020]. J Infect Dis. doi:10.1093/infdis/jiaa100