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We read with interest the article by Hedskog et al. on characterization of intergenotypic recombinant hepatitis C viruses (HCV) and their potential impact on genotype determination and subsequent response to genotype-dependent combination therapies based on direct-acting agents (DAAs).(1) In this work, 2.5% of HCV classified genotype 2 based on 5 0 untranslated region (UTR) sequencing or INNO-LiPA were revealed as being HCV-1 based on nonstructural (NS)5b-polymerase gene analysis. We searched in our IHU clinical microbiology laboratory sequence database for such discordance between genotype determined based on phylogeny of 5 0 UTR and NS3-protease or NS5b regions. 0 UTR/NS5b sequences were concurrently obtained from a same sample for 145 and 446 patients, respectively. These sequences were compared by BLAST and phylogeny to reference sequences of HCV genotypes that included recombinants identified by Hedskog et al.(1) In 35 cases, genotype was 2 according to 5 0 UTR phylogeny, and a NS3 or NS5b sequence was concurrently obtained in 9 and 28 cases, respectively. For 2 patients, genotype was 1 according to NS3 gene phylogeny and HCV NS3 sequence was clustered with a HCV 2k/1b recombinant ( Fig. 1; Supporting Information). Hence, in our cohort, such discrepancy regarding HCV genotype determination involved 5.7% of 5 0 UTR sequences of genotype 2. Such misclassifications of 5 0 UTR sequences for HCV 2k/1b recombinant strains were also reported recently in Belgium. (5) We further performed NS3 phylogeny reconstruction with sequences from our database for which a HCV 2/ 1 recombinant was the best BLAST hit and identified sequences that were clustered with 2k/1b or 2b/1b recombinants for 7 patients, who included those 2 we formerly identified as infected with HCV 2k/1b recombinant strains (Supporting Information).Although coinfections by different HCV cannot be completely ruled out here because clonal full-length genomes were not generated in routine clinical practice, our data suggest that HCV-2/1 recombinants circulate in our geographical area and, in addition to previous reports of inaccurate 5 0 UTR-based HCV classification,that CORRESPONDENCE HEPATOLOGY,

This retrospective and longitudinal study evaluated the long-term hepatic tolerance of a nelfinavir (NFV)-antiretroviral combined regimen in 82 patients of the HCV-HIV Cohort of CISIH-Sud of Marseilles. Follow-up data (liver enzyme levels, CD4 cell count, HIV viral load, and metabolic parameters) of patients treated with NFV on inclusion or during the follow-up of the cohort were analyzed under treatment over 24 months. Comparisons were performed with X2 or Kruskal-Wallis tests. At baseline (n = 82), the median exposure to NFV was 4.1 months; 58 patients received NFV combined with NRTI and 24 with NNRTI. The median CD4 cell count was 337/mm3 [interquartile range (IR): 216-480) and 39.7% had an undetectable HIV RNA level. Qualitative HCV PCR was positive in 91% of the patients and 19/51 patients with liver biopsy were F3-F4. Median alanine and aspartate aminotransferase (ALAT, ASAT), gamma-glutamyltransferase (GT), and alkaline phosphatase (ALP) were 46 UI/liter (IR: 36-76), 55 UI/liter (IR: 32-97), 97 UI/liter (IR: 50-194), and 88 UI/liter (IR: 72-104), respectively, with 76% of the patients with ALAT/ASAT grade <2. Median follow-up was 23 months (IR: 13.8-37). No significant difference was observed in the distribution of ALAT, ASAT, GT, and ALP as well as of ALAT/ASAT grades over the 24-month study period. Patients treated with NFV + NNRTI had significantly higher GT and ALP levels at baseline with no significant increase during follow-up. Cholesterol, triglyceride, and glycemia distributions remained stable over time. In conclusion, this study showed a good hepatic and metabolic tolerance of a long-term NFV-combined regimen in HIV-HCV coinfected patients.

HCV therapy associating interferon and ribavirin in HCV-HIV coinfected patients is well accepted even if tolerance is moderate. Treatment permitted SVR in at least 17% of the cases. This is likely when patients initiate treatment at the early fibrosis stage and are infected with genotype 3a. The potential interaction with PI therapy should be explored.