• Sabrina Bagaglio, Caterina Uberti-Foppa, Clelia Di Serio, Filippo Trentini, Andrea Andolina, Hamid Hasson, Emanuela Messina, Marco Merli, Lucy Porrino, Adriano Lazzarin, and Giulia Morsica.
• Infectious Diseases Department, Scientific Institute Ospedale San Raffaele, Via Stamira d'Ancona 20, 20127 Milan, Italy (SB, CU-F, AA, HH, EM, MM, AL, GM); Vita-Salute University Via Olgettina 58, 20132 Milan, Italy (SB, AL); University Centre for Statistics in the Biomedical Sciences (CUSSB) Vita-Salute San Raffaele University, Via Olgettina 58, 20132 Milan, Italy (CDS, FT); L. Bocconi University, Via R. Sarfatti 25, 20136 Milan, Italy (FT); Mol Med Spa, Via Olgettina 58, 20132 Milan, Italy (LP).
• Medicine (Baltimore). 2015 Oct 1; 94 (43): e1876e1876.

AbstractThe extent of mixed hepatitis C virus (HCV) genotype in different compartments (plasma and peripheral blood mononuclear cell, PBMC) and possible association with treatment efficacy in HIV/HCV coinfected patients remains to be unknown.The objective of this study was to elucidate the frequency of mixed genotype infection (MG), its profile in different compartments during anti-HCV treatment, and the possible influence of different genotypes on the response rate.The compartmentalization of HCV population was investigated by next-generation sequencing in 19 HIV/HCV coinfected patients under anti-HCV treatment with peginterferon/ribavirin (P-R). Ten individuals were nonresponder (NR) or relapser (RE) to P-R treatment and 9 had a sustained virological response (SVR).Eleven/nineteen (58%) patients had MG in plasma compartment. Ten or 12 patients infected by a difficult to treat genotype (DTG) 1 or 4 as dominant strain, had an MG, whereas only 1/7 individuals infected by easy to treat genotype (ETG) harbored a mixed genotype, P = 0.006. HCV-RNA was more frequently detected in PBMC of NR (10/10) than in those of SVR (5/9), P = 0.032. Mixed genotype infection was detected in 6/15 (40%) PBMC-positive cases and was not associated with P-R treatment response. By multivariate analysis, MG in plasma samples was the most important viral factor affecting the treatment response (P = 0.0237).Detection of MG in plasma of HIV/HCV coinfected patients seems to represent the major determinant of response to P-R treatment. This finding may have important clinical implication in light of the new therapeutic approach in HIV/HCV coinfected individuals suggesting that combination treatment with direct acting antivirals could be less effective in MG.

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