Optimal cure rate by personalized HCV regimens in real-life: a proof-of-concept study

Cento, Valeria; Aragri, M.; Teti, Elisabetta; Polilli, Ennio; Bertoli, Ada; Foroghi, L.; Barbaliscia, Silvia; Maio, V.C. Di; Pieri, Alessandro; Palitti, Valeria Pace; Sarmati, Loredana; Parruti, Giustino; Andreoni, Massimo; Perno, Carlo Federico; Ceccherini‐Silberstein, Francesca

doi:10.1093/jac/dkx302

Cited by 10 publications

(9 citation statements)

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“…The presence of substitutions conferring resistance to NS5A inhibitors has been widely reported both in therapy-naïve and in relapser patients from Europe [ 10 , 33 , 35 – 38 ], USA [ 37 , 39 , 40 ], and Asia [ 41 – 43 ]. However, NS5A sequences from South America are poorly analyzed yet [ 9 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…The presence of baseline NS5A RASs impacts treatment outcome in some patient groups by affecting SVR rates. The detection of NS5A preexistent RASs may play a relevant role in the choice of first-line treatment regimens or in the simplification/shortening of recommended regimens, in order to bring SVR rates close to the highest achievable [ 27 , 38 , 41 , 53 ], in particular in countries such as Uruguay, where only two different DAA-containing treatment regimens are approved for their use.…”

Section: Discussionmentioning

confidence: 99%

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Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients

et al. 2018

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Hepatitis C Virus (HCV) infection treatment has dramatically changed with the advent of direct-acting antiviral agents (DAAs). However, the efficacy of DAAs can be attenuated by the presence of resistance-associated substitutions (RASs) before and after treatment. Indeed, RASs detected in DAA treatment-naïve HCV-infected patients could be useful for clinical management and outcome prediction. Although the frequency of naturally occurring HCV NS5A and NS5B RASs has been addressed in many countries, there are only a few reports on their prevalence in the South American region. The aim of this study was to investigate the presence of RASs to NS5A and NS5B inhibitors in a DAA treatment naïve cohort of Uruguayan patients infected with chronic hepatitis C and compare them with reports from other South American countries. Here, we found that naturally occurring substitutions conferring resistance to NS5A and NS5B inhibitors were present in 8% and 19.2%, respectively, of treatment-naïve HCV genotype 1 infected patients. Importantly, the baseline substitutions in NS5A and NS5B herein identified differ from the studies previously reported in Brazil. Furthermore, Uruguayan strains subtype 1a clustered within all major world clades, showing that HCV variants currently circulating in this country are characterized by a remarkable genetic diversity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients

et al. 2018

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“…Recently, a real-life study reported how 130 DAA naïve HCV-infected patients who received baseline RASs guided therapy achieved 100% of SVR12 9 . The authors concluded that this strategy could help to minimize or eliminate relapses.…”

Section: Discussionmentioning

confidence: 99%

“…Cento et al . 9 reported 100% sustained virological response (SVR) rate in DAA-naïve patients undergoing treatment guided by baseline RASs in clinical practice. Nonetheless, they did not compare with a control population without RAS-guided treatment.…”

Section: Introductionmentioning

confidence: 99%

Baseline resistance-guided therapy does not enhance the response to interferon-free treatment of HCV infection in real life

Real

Macı́as

Pérez

et al. 2018

Sci Rep

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Hepatitis C virus (HCV) response to direct-acting antivirals (DAAs) may be influenced by the presence of resistance-associated substitutions (RASs). This study aimed to assess if NS5A baseline RAS-guided treatment enhances the rate of sustained viral response (SVR) in naïve HCV-infected patients in clinical practice. All HCV-infected patients who initiated treatment with interferon (IFN)-free DAA-based regimens between March 2016 and May 2017 in 17 Spanish hospitals and who had evaluable SVR 12 weeks (SVR12) after the end of therapy were included. Patients had to be DAA naïve, with the exception of sofosbuvir with/without IFN. In one hospital, participants received therapy guided by the presence of NS5A-RASs (RGT population). Patients enrolled in the remaining hospitals, without baseline RASs testing, constituted the control population. A total of 120 and 512 patients were included in the RGT and control populations, respectively. Nine (7.5%) individuals in the RGT population showed baseline NS5A-RASs. All of them achieved SVR12. The SVR12 rate in the RGT population was 97.2% (three relapses) whereas it was 98.8% (six relapses) in the control population (p = 0.382). Our findings suggest that testing for baseline NS5A-RASs in naïve HCV-infected patients does not enhance the rate of SVR to DAA-based IFN-free therapy in clinical practice.

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“…Even with newer DAAs, for instance, patients with GT3 infection and natural RASs may more frequently experience virological failure 13 , 14 . Under these conditions, a tailored approach in some (not infrequent, though) real-life situations may help in bringing the cure rate closer to the 98–99% 5 , 9 , 11 , 15 .…”

Section: Introductionmentioning

confidence: 99%

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

Bertoli¹,

Sorbo²,

Aragri³

et al. 2018

Sci Rep

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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.

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Optimal cure rate by personalized HCV regimens in real-life: a proof-of-concept study

Cited by 10 publications

References 10 publications

Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients

Pretreatment Hepatitis C Virus NS5A/NS5B Resistance-Associated Substitutions in Genotype 1 Uruguayan Infected Patients

Baseline resistance-guided therapy does not enhance the response to interferon-free treatment of HCV infection in real life

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

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