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Sci Rep. 2018 Jun 12;8(1):8988. doi: 10.1038/s41598-018-26862-y.

Prevalence of Single and Multiple Natural NS3, NS5A and NS5B Resistance-Associated Substitutions in Hepatitis C Virus Genotypes 1-4 in Italy.

Author information

1
Department Experimental Medicine and Surgery, University of Rome "Tor Vergata", 00133, Rome, Italy.
2
Hepatology Unit, University Hospital of Rome "Tor Vergata", 00133, Rome, Italy.
3
Infectious Diseases Unit, University Hospital of Rome "Tor Vergata", 00133, Rome, Italy.
4
Infectious Diseases Unit, Pescara General Hospital, 65124, Pescara, Italy.
5
Infectious Diseases Unit, Sant'Andrea Hospital - "Sapienza" University, 00189, Rome, Italy.
6
Tropical Diseases, Umberto I Hospital -"Sapienza" University, 00161, Rome, Italy.
7
1st Division of Infectious Diseases, ASST Fatebenefratelli Sacco, 20157, Milan, Italy.
8
Clinical and Experimental Medicine, University of Sassari, 07100, Sassari, Italy.
9
Infectious Diseases Unit, IRCCS AOU San Martino - IST, 16132, Genoa, Italy.
10
Hepatology Unit, San Camillo Forlanini Hospital, 00151, Rome, Italy.
11
Molecular Virology, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy.
12
Gastroenterology, "P. Giaccone" University Hospital, 90127, Palermo, Italy.
13
Gastroenterology, "Federico II" University, 80131, Naples, Italy.
14
Hepatology Unit, Pescara General Hospital, 65124, Pescara, Italy.
15
Gastroenterology, Catholic University of Rome, 00168, Rome, Italy.
16
Infectious Diseases Unit, "L. Vanvitelli" University of Campania, 80138, Naples, Italy.
17
Infectious Diseases Unit, S. Salvatore Hospital, 67100, L'Aquila, Italy.
18
Infectious Diseases Unit, Niguarda Ca' Granda Hospital, 20162, Milan, Italy.
19
Haematology and Oncohematology, University of Milan, 20122, Milan, Italy.
20
Department Experimental Medicine and Surgery, University of Rome "Tor Vergata", 00133, Rome, Italy. valeriacento@gmail.com.

Abstract

Natural resistance-associated substitutions (RASs) are reported with highly variable prevalence across different HCV genotypes (GTs). Frequency of natural RASs in a large Italian real-life cohort of patients infected with the 4 main HCV-GTs was investigated. NS3, NS5A and NS5B sequences were analysed in 1445 HCV-infected DAA-naïve patients. Sanger-sequencing was performed by home-made protocols on 464 GT1a, 585 GT1b, 92 GT2c, 199 GT3a, 16 GT4a and 99 GT4d samples. Overall, 20.7% (301/1455) of patients showed natural RASs, and the prevalence of multiclass-resistance was 7.3% (29/372 patients analysed). NS3-RASs were particularly common in GT1a and GT1b (45.2-10.8%, respectively), mainly due to 80K presence in GT1a (17%). Almost all GTs showed high prevalence of NS5A-RASs (range: 10.2-45.4%), and especially of 93H (5.1%). NS5A-RASs with fold-change >100x were detected in 6.8% GT1a (30H/R-31M-93C/H), 10.3% GT1b (31V-93H), 28.4% GT2c (28C-31M-93H), 8.5% GT3a (30K-93H), 45.5% GT4a (28M-30R-93H) and 3.8% GT4d (28V-30S-93H). Sofosbuvir RAS 282T was never detected, while the 159F and 316N RASs were found in GT1b (13.4-19.1%, respectively). Natural RASs are common in Italian patients infected with HCV-GTs 1-4. High prevalence of clinically-relevant RASs (such as Y93H) supports the appropriateness of HCV resistance-test to properly guide DAA-based therapy.

PMID:
29895871
PMCID:
PMC5997636
DOI:
10.1038/s41598-018-26862-y
[Indexed for MEDLINE]
Free PMC Article

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