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Purpose Globally, it is estimated that 71 million people are chronically infected with hepatitis C, and 10–20% of these will develop cirrhosis and hepatocellular carcinoma. The development of new direct-acting antiviral (DAA) drugs has contributed to sustained virological response (SVR), eliminating the infection and achieving cure of chronic hepatitis C. However, treated patients can develop HCV resistance to DAAs, which can contribute to the failure of treatment. Here, we aimed to evaluate the prevalence and specific pattern of NS5A and NS5B resistance-associated substitutions (RAS) in samples from patients chronically infected with HCV genotype 3a at a public health laboratory, Instituto Adolfo Lutz, São Paulo, Brazil. Patients and Methods Serum samples from the enrolled individuals were submitted to “in-house” polymerase chain reaction amplification of NS5A and NS5B non-structural protein genes, which were then sequenced by Sanger method. Results A total of 170 and 190 samples were amplified and analyzed for NS5A and NS5B, respectively. For NS5A, 20 (12.0%) samples showed some important RAS; 16 (9.0%) showed some type of substitution and 134 (79.0%) showed no polymorphism. No sample showed any RAS for NS5B. Conclusion This study found important RAS in samples from naïve chronic HCV patients in some areas from São Paulo. The most prevalent were A62S, A30K, and Y93H, which could indicate an increase in resistance to some DAAs used in HCV treatment.

Introduction: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) have identical transmission routes, explaining the high prevalence of coinfections. The main aim of this study was to detect fluctuations in serological HCV levels in HIV patients. Methods: We analyzed samples of 147 patients who attended an outpatient service that supports HIV/AIDS patients in São Paulo city. We also recruited 22 HCV-monoinfected patients who attended the Instituto Adolfo Lutz Laboratory in São Paulo city, to compare the test results. Serological testing of the blood samples was performed for the detection of HCV antibodies. The samples were then analyzed using real-time PCR for RNA viral quantification and sequencing. Results: We found that 13.6% of the study population was coinfected with HIV and HCV. In 20% of coinfected patients, fluctuations in serology results were detected in samples collected during the follow-up. No changes in anti-HCV serological markers were observed in HCV-monoinfected patients. An HCV viral load was detected in 9,5% of the samples collected from HIV patients. Conclusions: Our findings provide important clinical data to public health professionals and highlight the importance of periodic monitoring of HCV/HIV coinfected patients.

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Hepatitis C virus (HCV) infection is a public health problem with an estimated 71 million infected people worldwide. The high level of HCV replication and its lack of post - transcriptional correction mechanisms result in the rapid emergence of viral variants, difficulty in determining polymorphisms, and variants that contain substitutions associated with resistance and/or reduction of susceptibility towards new antivirals. The aim of this study was to map the polymorphisms in NS5A and NS5B and resistance mutations to new antiviral drugs in HCV strains with genotype 1a and 1b derived from patients with chronic hepatitis C infection. Serum samples from patients who underwent routine viral load tests and monitoring at the laboratory of viral hepatitis at the Adolfo Lutz Institute, São Paulo, Brazil were collected. A total of 698 and 853 samples were used for the characterization of NS5A and NS5B regions respectively; comprising HCV genotypes 1a and 1b. The prevalence of resistance mutations in the NS5A region was found to be 6.4%, with Y93H, L31M, Q30R, and Y93N as the main resistance-associated substitutions (RAS). No NS5B- associated RAS was observed for any of the drugs analyzed. This study reveals the presence of significant RAS in the HCV serum samples. These findings support the RAS test should be offered to individuals with poor response to double combination regimens prior to treatment initiation, thereby assisting strain vigilance and selection of effective treatment or retreatment options using DAA regimens.