Full-Genome Analysis of Hepatitis C Virus in Japanese and Non-Japanese Patients Coinfected With HIV-1 in Tokyo

Abstract

Background: Acute hepatitis C virus (HCV) infection is increasing among HIV-1–infected individuals in Tokyo. Appropriate clinical management is needed. Setting: To delineate the epidemiological status of HCV transmission, we analyzed stocked plasma samples of HCV/HIV-1–coinfected patients seen at the largest referral center for HIV care in Tokyo. Methods: HCV full-genome sequences were amplified and determined using next-generation sequencing. HCV genotyping and phylogenetic and phylodynamic analyses of thus obtained sequences were performed and combined with the analysis of HIV-1 reverse transcriptase sequences. Results: HCV phylogenetic analysis identified 3 dense clusters containing cases of men who have sex with men (MSM) and injection drug users (IDUs). Most of the confirmed acute infection cases were included within these clusters, indicating that the clustered viruses are currently being actively transmitted among HIV-1–infected MSM and IDU. Phylodynamic analysis indicated population expansion of one of these clusters from 2006 to 2008, during which the largest number of HIV-1–infected MSM was diagnosed in Tokyo. HIV-1 reverse transcriptase sequences of HCV-coinfected patients included in the same clusters did not converge together and did not form clusters, but rather diverged in the area of subtype B in the phylogenetic tree, indicating that they acquired HCV infection from individuals different from those from whom they had acquired HIV-1 infection. It is considered that these MSM changed their sexual partners and that IDU changed their drug use groups. Conclusions: The results warrant careful monitoring of high-risk groups including MSM and IDU and early introduction of HCV treatment to prevent HCV epidemic.

Full‐genome analysis of hepatitis C virus in HIV‐coinfected hemophiliac Japanese patients

“…1, column 4) 9 and our group (Fig. 1, column 3) 10 in non‐hemophiliac Japanese patients, but they seemed similar to those in the USA (Fig. 1, column 1) 18 …”

“…Hepatitis C virus genotype prevalence in HIV‐coinfected hemophiliac (column 2) and non‐hemophiliac Japanese patients (column 3) 10 compared with those in the USA (column 1) 18 and the general Japanese population (column 4) 9 . A single case (#049) infected with mixed genotypes (1a and 3a) was counted in both genotypes in HIV‐coinfected hemophiliac Japanese patients.…”

“…3). 10 The sequences of each genotype converged away from other genotypes, confirming the abovementioned genotypes determined using COMET 15 and the HCV Subtyping Tool at BioAfrica 16 . All the analyzed sequences of the hemophiliac patients were more than 0.05 genetic distance away from the other sequences of hemophiliac and non‐hemophiliac Japanese patients and none was included in any of the three dense clusters of HCV sequences of non‐hemophiliac patients described in our previous study (clusters A, B, and C), 10 indicating that the HCV strains of hemophiliacs were not transmitted to others in Japan and that viral evolution had continued in each patient after infection.…”

“…The thus obtained sequences were phylogenetically analyzed with 77 reference sequences. The reference sequences were derived from Japanese non‐hemophiliac HCV/HIV‐coinfected patients analyzed by the same methods in our previous study, including 52 men who have sex with men, 14 injection drug users, and 11 heterosexually infected patients 10 . Multiple alignments was performed using C lustal W 17 through mega7 .…”

“…In Japan, HCV 1b is the main prevalent genotype followed by HCV 2a in the general population 9 . We previously reported comparable HCV genotype frequencies in HIV‐coinfected non‐hemophiliac Japanese patients 10 . However, the above group of hemophiliac patients acquired HCV and HIV infections through different transmission routes (contaminated blood products imported from the USA).…”