Abstract:

The estimated prevalence of HCV infection in Argentina is around 2%. However, higher rates of infection have been described in population studies of small urban and rural communities. The aim of this work was to compare the origin and diversification of HCV-1b in samples from two different epidemiological scenarios: Buenos Aires, a large cosmopolitan city, and O´Brien, a small rural town with a high prevalence of HCV infection. PATIENTS AND METHODS: The E1/E2 and NS5B regions of the viral genome from 83 patients infected with HCV-1b were sequenced. Phylogenetic analysis and Bayesian Coalescent methods were used to study the origin and diversification of HCV-1b in both patient populations. RESULTS: Samples from Buenos Aires showed a polyphyletic behavior with a tMRCA around 1887-1900 and a time of spread of infection approximately 60 years ago. In contrast, samples from ÓBrien showed a monophyletic behavior with a tMRCA around 1950-1960 and a time of spread of infection more recent than in Buenos Aires, around 20-30 years ago. CONCLUSION: Phylogenetic and coalescence analysis revealed a different behavior in the epidemiological histories of Buenos Aires and ÓBrien. HCV infection in Buenos Aires shows a polyphyletic behavior and an exponential growth in two phases, whereas that in O´Brien shows a monophyletic cluster and an exponential growth in one single step with a more recent tMRCA. The polyphyletic origin and the probability of encountering susceptible individuals in a large cosmopolitan city like Buenos Aires are in agreement with a longer period of expansion. In contrast, in less populated areas such as O´Brien, the chances of HCV transmission are strongly restricted. Furthermore, the monophyletic character and the most recent time of emergence suggest that different HCV-1b ancestors (variants) that were in expansion in Buenos Aires had the opportunity to colonize and expand in O´Brien.

Author affiliation: Golemba, Marcelo Darío. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Microbiologia,inmunologia y Biotecnolog.;

Author affiliation: Culasso, Andrés Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Microbiologia,inmunologia y Biotecnolog.. Cat. de Virologia;

Author affiliation: Villamil, Federico. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad En Red El Cruce Dr. Nestor Carlos Kirchner Samic;

Author affiliation: Baré, Patricia. Consejo Nacional de Invest.cientif.y Tecnicas. Instituto de Medicina Experimental;

Author affiliation: Gadano, Adrián Carlos. Htal.italiano;

Author affiliation: Ridruejo, Ezequiel. Centro de Educaciones Medicas E Investig.clinica "norberto Quirno";

Author affiliation: Martínez, Alfredo. Centro de Educaciones Medicas E Investig.clinica "norberto Quirno";

Author affiliation: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Microbiologia,inmunologia y Biotecnolog.. Cat. de Virologia;

Author affiliation: Campos, Rodolfo Hector. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Departamento de Microbiologia,inmunologia y Biotecnolog.;

Abstract:

Incorporation of direct acting antivirals (DAA) in the treatment of Hepatitis C Virus (HCV) significantly increases sustained virologic response rates. However, despite the greater potency offered by these antivirals, drug resistance plays a key role in patients with failure to DAA. Nevertheless, there is no information about the prevalence of resistance-associated substitutions (RASs) in Argentina. The aim of this study was to analyze HCV variants resistant to protease inhibitors (PI) in naïve patients infected with HCV genotype 1 from Argentina. In this retrospective cross-sectional study, 103 patients infected with HCV-1 were included. Eighteen positions related with RASs were analyzed by Sanger at baseline and phylogenetic analysis was performed to determine the diversification of this samples. The analyzed RASs were present in 38 out of 103 patients (36.9%) infected with HCV-1. Patients infected with subtype HCV-1b had higher prevalence of baseline RASs than patients infected with HCV-1a [51.6% vs. 12.8%, respectively (p < 0.001)]. The Q80K polymorphism was not found in HCV-1a samples, even when 51% of them belonged to cluster 1, which is associated with a high frequency of Q80K. Phylogenetic analysis showed that Argentinean samples were intermingled with sequences from other geographic regions. RASs to PI were highly prevalent and subtype dependent in treatment-naïve Argentinean patients. Surprisingly, Q80K polymorphism was not detected in our study population. The phylogenetic analysis showed no relationship between our samples and other samples from Brazil which also present a low prevalence of Q80K. This study supports the need for surveillance of resistance in patients who will be treated with DAA in each particular country since the observed RASs have very different prevalence worldwide.

Author affiliation: Martínez, Alfredo P.. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina

Author affiliation: Culasso, Andrés Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

Author affiliation: Pérez, Paula Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

Author affiliation: Romano, Vanesa. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina

Author affiliation: Campos, Rodolfo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

Author affiliation: Ridruejo, Ezequiel. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; Argentina

Author affiliation: García, Gabriel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

Author affiliation: Di Lello, Federico Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

Abstract:

Hepatitis C virus (HCV) screening according to the year of birth is recommended is some countries based on epidemiological data. The aim of this study was to analyze anti-HCV prevalence among people born between 1905 and 2015 in Argentina. Patients attending a tertiary care hospital in Buenos Aires, Argentina, from 2001 to 2015, who had a determination of anti-HCV, were included. Of 22,079 patients analyzed, 1,152 (5.2%; 95% confidence interval [CI]: 4.9%–5.5%) patients showed positive anti-HCV and 729 (3.3%; 95% CI: 3.1%–3.5%) patients showed detectable viremia. Three risk groups were identified (HCV prevalence): low-risk group—outpatient clinics/emergencies (2.8%); intermediate-risk group—in-patients (8%); and high-risk group—dialysis/transplants (27.2%). In the low-risk group, being born in 1973 or before was identified as a cut-off value for the risk of anti-HCV acquisition (area under the receiver-operator characteristic curve: 75.1 [95% asymptotic CI: 0.732–0.770; p < 0.001]). Ninety-one patients born after 1973 (0.8%) showed positive anti-HCV versus 457 individuals born in 1973 or before (5.8%), p < 0.001. In this group, positive anti-HCV was observed in 252 females (2.1%) and 296 males (4.1%), p < 0.001. In a multivariate analysis adjusted for gender, alanine-aminotransferase levels and HIV coinfection, being born in 1973 or before was independently identified as a risk for positive anti-HCV (adjusted odds ratio: 14.234 [95% CI: 9.993–20.277]; p < 0.001). People born in 1973 or before without other risk factors should be included in screening programs to link the highest possible number of HCV-infected patients to appropriate care and treatment.

Author affiliation: Neukam, K.. Consejo Superior de Investigaciones Científicas; España. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

Author affiliation: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET.; Argentina

Author affiliation: Pérez, Paula Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

Author affiliation: Campos, Rodolfo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina

Author affiliation: Martínez, A. P.. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno”; Argentina

Author affiliation: Di Lello, Federico Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina