Download PDF

International Workshop on HIV and Hepatitis Co-infection, Date: 2017/06/21 - 2017/06/23, Location: Lisbon, Portugal

Publication date: 2017-06-22

Author:

Cuypers, Lize
Pérez, Ana Belen ; Chueca, Natalia ; Aldamiz-Echevarria, T ; Alados, JC ; Martinez-Sapina, AM ; Merino, D ; Pineda, JA ; Téllez, F ; Viciana, P ; Salmeron, FJ ; Rivero-Juarez, A ; Vivancos, MJ ; Hontanon, V ; Vandamme, Anne-Mieke ; Garcia, Féderico

Abstract:

Background: Despite high response rates associated to DAA treatment, no protective immunity is acquired, so patients that are cured after treatment can be infected with a new HCV strain, and therefore may be responsible for further transmission. Consequently, viral eradication may be hampered by high reinfection and transmission rates among patients with persistent risk behaviour. Distinguishing between virological relapse and reinfection is crucial to determine the true efficacy of current therapies and to define the most appropriate retreatment if needed. Methods: The GEHEP-004 cohort includes approximately 300 patients failing to different DAA regimens from 42 Spanish centers. For 53 patients treated between 2014 and 2016, the virus was sampled at two time points, before start of therapy and at time of failure. Sequencing was performed for two or three regions (NS3 – NS5A – NS5B), depending on the DAA regimen administered. For each taxon, the ten most similar sequences were retrieved from public databases by the use of BLAST. Concatenated alignments were used to infer phylogenetic trees by neighbour-joining and maximum-likelihood algorithms, with the GTR gamma model and 1000 bootstrap replicates. When comparing strains before and after treatment in one patient, evidence of reinfection was defined as a difference in HCV genotype or subtype, or as a significantly different clustering in distant clades in the tree. Evidence of relapse was defined as significant clustering in the same clade, while no conclusion was drawn when clades were supported with a bootstrap < /70%. Simplot was used to detect recombination. Results: Genotype assignment by phylogenetic analysis revealed nine discordant cases (17.0%) with commercial assays at genotype and subtype level, while no recombinants were identified. At baseline, 41.5% of patients were determined to be infected with HCV1a, followed by HCV1b (24.5%), HCV4 (18.9%) and HCV3a (15.1%). Overall, 60.4% was co-infected with HIV. The large majority of patients for which the transmission route of infection was known, was classified as people who inject drugs (PWID) (78.6%), often co-infected with HIV (27/33) and half of them infected with HCV1a. Sexual transmission was observed in seven cases, of which five in HIV-positive men who have sex with men (MSM). Due to poor phylogenetic signal of single fragments, conclusions were only drawn for concatenated alignments. Overall, five patients were reinfected with a different HCV strain (4 PWID + 1 MSM), of which three with a different HCV genotype or subtype, and four co-infected with HIV. Virological relapse was defined for 44 patients, while no conclusion could be drawn for four patients. Conclusions: In our cohort, the majority of patients experienced a virological relapse. Almost 10% were reinfected, most of them PWID and HIV co-infected. Since about half of those reinfected, showed the same subtype as at baseline, phylogenetics is needed, not only to determine the correct HCV genotype, but also to distinguish between relapse and reinfection. Of note, phylogenetic analysis can only result in confident conclusions when long genomic stretches with sufficient phylogenetic signal are available, stressing the need to perform full-genome sequencing or to concatenate multiple regions.