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Viral dynamics among HCV infected patients with different genotypes treated with genotypic specific or pan-genotypic direct-acting antiviral agent combinations

Authors Paolucci S, Novazzi F, Piralla A, Maserati R, Gulminetti R, Novati S, Barbarini G, Sacchi P, Fratini A, Bellotti L, Baldanti F

Received 14 February 2019

Accepted for publication 25 March 2019

Published 8 July 2019 Volume 2019:12 Pages 1975—1984

DOI https://doi.org/10.2147/IDR.S205282

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 2

Editor who approved publication: Professor Suresh Antony


Stefania Paolucci,1 Federica Novazzi,1 Antonio Piralla,1 Renato Maserati,2 Roberto Gulminetti,2 Stefano Novati,2 Giorgio Barbarini,3 Paolo Sacchi,3 Alice Fratini,1 Laura Bellotti,1 Fausto Baldanti1,4

1Molecular Virology Unit, Microbiology and Virology Department, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico, San Matteo, Pavia, Italy; 2Institute of Infectious Diseases, University of Pavia, Pavia, Italy; 3Division of Infectious and Tropical Diseases, Fondazione IRCCS Policlinico, San Matteo, Pavia, Italy; 4Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy

Background: New hepatitis C virus (HCV) therapies have improved efficacy, allowed pangenotypic applications, increased barriers to drug resistance and shortened therapy duration.
Methods: Patients infected with different HCV genotypes were divided into two groups: group 1 included 169 patients receiving genotypic specific regimens (GSR), while group 2 included 186 patients receiving pan-genotypic regimens (PGR). Patient’s HCV RNA was quantified and sequenced.
Results: Comparable sustained viral response (SVR) rates were observed in both GSR and PGR treated patients. Nevertheless, even if not significant, a greater proportion of non-detectable levels (NDL) of HCV RNA was observed in patients treated with PGR as compared with GSR. Overall, among patients in the GSR and PGR groups with residual viremia, 124/169 (73.4%) and 125/186 (67.2%) at four weeks, and 66/169 (39.1%) and 58/186 (31.2%) at eight weeks, achieved SVR. No difference was observed in the clinical outcome comparing patients in the GSR and PGR groups according to genotype. While, comparing patients between the two groups, the proportion of patients with NDL HCV RNA at four and eight weeks was higher in patients infected with genotype 1b treated with PGR (p=0.0015). A significantly higher number of patients infected with 1b had RASs at baseline (p=0.0001). In addition, the proportion of patients with treatment failure was higher in patients with RASs at baseline compared with those without (p=0.012). Overall, 2.5% patients failed to achieve SVR after DAA treatment.
Conclusion: A sharp HCV RNA decrease was observed in patients treated with both GSR and PGR. However, even if comparable, a slightly greater number of patients treated with PGR achieved NDL HCV RNA as compared with GSR. A significant difference was observed in patients with baseline RASs, both in relation to treatment failure and genotype. In conclusion, the use of new DAA combinations helps patients achieve a more rapid virologic response.

Keywords: hepatitis C virus, drug resistance, DAA inhibitors, viral dynamics, treatment failure


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