Outbreak of Infections by Hepatitis B Virus Genotype A and Transmission of Genetic Drug Resistance in Patients Coinfected with HIV-1 in Japan
Ontology highlight
ABSTRACT:
SUBMITTER:
PROVIDER: S-EPMC3318497 | biostudies-literature | 2012 Apr
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:The major routes of hepatitis B virus (HBV) infection in Japan has been mother-to-child transmission (MTCT) and blood transfusion. However, HBV cases transmitted through sexual contact are increasing, especially among HIV-1-seropositive patients. To understand the molecular epidemiology of HBV in HBV/HIV-1 coinfection, we analyzed HBV genotypes and HIV-1 subtypes in HBV/HIV-1-coinfected patients at Nagoya Medical Center from 2003 to 2007. Among 394 HIV-1-infected Japanese men having sex with men (MSM) who were newly diagnosed during the study period, 31 (7.9%) tested positive for the hepatitis B virus surface antigen. HBV sequence analyses were successful in 26 cases, with 21 (80.7%) and 5 (19.3%) cases determined as genotypes A and C, respectively. Our finding that HBV genotype A was dominant in HIV-1-seropositive patients alerts clinicians to an alternative outbreak of HBV genotype A in the HIV-1-infected MSM population and a shift in HBV genotype from C to A in Japan. The narrow genetic diversity in genotype A cases suggests that genotype A has been recently introduced into the MSM population and that sexual contacts among MSM were more active than speculated from HIV-1 tree analyses. In addition, we found a lamivudine resistance mutation in one naïve case, suggesting a risk of drug-resistant HBV transmission. As genotype A infection has a higher risk than infection with other genotypes for individuals to become HBV carriers, prevention programs are urgently needed for the target population.
| S-EPMC3067677 | biostudies-literature
Project description:Hepatitis B virus (HBV) genotypes were examined in HIV-infected patients with chronic and occult HBV infection. From a total population of 593 HIV-infected patients, 22 individuals (prevalence 3.7%) were found to be HBsAg while 72 (12.1%) were found to be anti-HBc alone. From them, 20 and 4 were HBV DNA positive, respectively. These last four patients are therefore considered to be HBV infected in an occult form. The genotypes could be determined in all 24 HBV-infected patients. HBV-A was the most common (20/24; 83.3%), followed by HBV-D (2/24; 8.3%) and HBV-F (1/24; 4.2%). The remaining sample exhibited mixed infection involving genotypes A and D as pure ones, thus also forming part of three intergenotypic recombinant forms exhibiting different mosaic S gene patterns. The sexual route of transmission was predominant among HBV genotype A-infected patients. Among the 24 HBV DNA-positive patients, point mutations related to lamivudine resistance were found in four strains. These viral strains showed a methionine-to-valine substitution at codon 204 (rtM204V) in association with an upstream B-domain change at rtL180M. Additionally, two of them exhibited the additional rtV173L mutation. The value of HBV molecular monitoring including both HBV viral genomic characterization and genotypic resistance profile in HIV-HBV-coinfected individuals is discussed.
| S-EPMC2894418 | biostudies-literature
Project description:BackgroundGlobal immune activation and HLA alleles are each associated with the pathogenesis of human immunodeficiency virus (HIV) and hepatitis C virus .MethodsWe evaluated the relationship between 44 HLA class I and 28 class II alleles and percentages of activated CD8 (CD8+CD38+DR+) and CD4 (CD4+CD38+DR+) T cells in 586 women who were naive to highly active antiretroviral therapy. We used linear generalized estimating equation regression models, adjusting for race/ethnicity, age, HIV load, and hepatitis C virus infection and controlling for multiplicity using a false discovery rate threshold of 0.10.ResultsTen HLA alleles were associated with CD8 and/or CD4 T-cell activation. Lower percentages of activated CD8 and/or CD4 T cells were associated with protective alleles B*57:03 (CD8 T cells, -6.6% [P = .002]; CD4 T cells, -2.7% [P = .007]), C*18:01 (CD8 T cells, -6.6%; P < .0008) and DRB1*13:01 (CD4 T cells, -2.7%; P < .0004), and higher percentages were found with B*18:01 (CD8 T cells, 6.2%; P < .0003), a detrimental allele. Other alleles/allele groups associated with activation included C*12:03, group DQA1*01:00, DQB1*03:01, DQB1*03:02, DQB1*06:02, and DQB1*06:03.ConclusionThese findings suggest that a person's HLA type may play a role in modulating T-cell activation independent of viral load and sheds light on the relationship between HLA, T-cell activation, immune control, and HIV pathogenesis.
| S-EPMC7325713 | biostudies-literature
Project description:BackgroundHIV/AIDS is a serious threat to public health. The emergence of drug resistance mutations diminishes the effectiveness of drug therapy for HIV/AIDS. Developing a computational prediction of drug resistance phenotype will enable efficient and timely selection of the best treatment regimens.ResultsA unified encoding of protein sequence and structure was used as the feature vector for predicting phenotypic resistance from genotype data. Two machine learning algorithms, Random Forest and K-nearest neighbor, were used. The prediction accuracies were examined by five-fold cross-validation on the genotype-phenotype datasets. A supervised machine learning approach for automatic prediction of drug resistance was developed to handle genotype-phenotype datasets of HIV protease (PR) and reverse transcriptase (RT). It predicts the drug resistance phenotype and its relative severity from a query sequence. The accuracy of the classification was higher than 0.973 for eight PR inhibitors and 0.986 for ten RT inhibitors, respectively. The overall cross-validated regression R(2)-values for the severity of drug resistance were 0.772-0.953 for 8 PR inhibitors and 0.773-0.995 for 10 RT inhibitors.ConclusionsMachine learning using a unified encoding of sequence and protein structure as a feature vector provides an accurate prediction of drug resistance from genotype data. A practical webserver for clinicians has been implemented.
| S-EPMC5009519 | biostudies-literature
Project description:Purpose of reviewTo review the experience to date and unique challenges associated with liver transplantation in hepatitis C virus (HCV)/HIV-coinfected patients.Recent findingsThe prevalence of cirrhosis and hepatocellular carcinoma is rising among HIV-infected individuals. With careful patient selection and in the absence of HCV infection, HIV-infected and HIV-uninfected liver transplant recipients have comparable posttransplant outcomes. However, in the presence of HCV infection, patient and graft survival are significantly poorer in HIV-infected recipients, who have a higher risk of aggressive HCV recurrence, acute rejection, sepsis, and multiorgan failure. Outcomes may be improved with careful recipient and donor selection and with the availability of new highly potent all-oral HCV direct acting antivirals (DAAs). Although all-oral DAAs have not been evaluated in HIV/HCV-coinfected transplant patients, HIV does not adversely impact treatment success in nontransplant populations. Therefore, there is great hope that HCV can be successful eradicated in HIV/HCV-coinfected transplant patients and will result in improved outcomes. Careful attention to drug-drug interactions with HIV antiretroviral agents, DAAs, and posttransplant immunosuppressants is required.SummaryLiver transplant outcomes are poorer in HIV/HCV-coinfected recipients compared with those with HCV-monoinfection. The new HCV DAAs offer tremendous potential to improve outcomes in this challenging population.
| S-EPMC4807723 | biostudies-literature
Project description:Despite significant advances in transplantation of HIV-infected individuals, little is known about HIV coinfected patients with hepatitis C virus (HCV) genotypes other than genotype 1, especially when receiving HCV-infected organs with a different genotype. We describe the first case of kidney transplantation in a man coinfected with hepatitis C and HIV in our state. To our knowledge, this is also the first report of an HIV/HCV/HBV tri-infected patient with non-1 (2a) HCV genotype who received an HCV-infected kidney graft with the discordant genotype (1a), to which he converted after transplant. Our case study highlights the following: (1) transplant centers need to monitor wait times for an HCV-infected organ and regularly assess the risk of delaying HCV antiviral treatment for HCV-infected transplant candidates in anticipation of the transplant from an HCV-infected donor; (2) closer monitoring of tacrolimus levels during the early phases of anti-HCV protease inhibitor introduction and discontinuation may be indicated; (3) donor genotype transmission can occur; (4) HIV/HCV coinfected transplant candidates require a holistic approach with emphasis on the cardiovascular risk profile and low threshold for cardiac catheterization as part of their pretransplant evaluation.
| S-EPMC7011348 | biostudies-literature
Project description:BackgroundLittle is known about the epidemiology of HIV in Japan, though newly-identified cases amongst men who have sex with men (MSM) show an increasing trend. Predictions of future trends in the HIV epidemic are essential to identify suitable interventions.MethodsA deterministic, compartmental model was developed that incorporated risk groups, disease stages, and treatment and testing parameters. This model was calibrated against current figures on new infections and run over 30 years to identify trends in prevalence amongst MSM, low-risk men and low-risk women. Multivariate sensitivity analysis was used to estimate sensitivity ranges for all outcomes.ResultsWithout new interventions amongst MSM in Japan, HIV prevalence will climb from its current rate of 2.1% to 10.4% (sensitivity range 7.4% to 18.7%), while HIV prevalence among low-risk men and women will likely decline. With small changes in safer sex behavior and testing rates, HIV prevalence can remain stable or even decline amongst MSM.ConclusionsJapan is at risk of an epidemic of HIV amongst MSM unless significant changes are made to its current public health intervention framework. More research is necessary to understand the key drivers of the epidemic in Japan.
| S-EPMC3423344 | biostudies-literature
Project description:BackgroundHepatitis E virus (HEV) infection is endemic in Bangladesh and there are occasional outbreaks. The molecular characteristics and pathogenesis of endemic and outbreak HEV strains are poorly understood. We compared the genetic relatedness and virulence associated mutations of endemic HEV strains with outbreak strains.MethodsWe analyzed systematically collected serum samples from HEV immunoglobulin M (IgM) positive patients attended at Bangabandhu Sheikh Mujib Medical University, Dhaka from August 2013 to June 2015. HEV RNA positive samples were subjected to whole genome sequencing. Genotype and subtype of the strains were determined by phylogenetic analysis. Virulence associated mutations e.g. acute viral hepatitis (AVH), fulminant hepatic failure (FHF), chronic hepatitis, ribavirin treatment failure (RTF), B and T cell neutralization epitopes were determined.Results92 HEV immunoglobulin M (IgM) antibody positive plasma samples (43 in 2013-2014 and 49 in 2014-2015) were studied. 77.1% (70/92) of the samples were HEV RNA positive. A 279 bp open reading frame (ORF) 2 and ORF 3 sequence was obtained from 54.2% (38/70) of the strains. Of these 38 strains, whole genome sequence (WGS) was obtained from 21 strains. In phylogenetic analysis of 38 (279 bp) sequence all HEV sequences belonged to genotype 1 and subtype 1a. Further phylogenetic analysis of 21 HEV WGS, Bangladeshi HEV sequences clustered with genotype 1a sequences from neighboring countries. Within genotype 1a cluster, Bangladesh HEV strains formed a separate cluster with the 2010 HEV outbreak strains from northern Bangladesh. 80.9 to 100% of the strains had A317T, T735I, L1120I, L1110F, P259S, V1479I, G1634K mutations associates AVH, FHF and RTF. Mutations in T cell recognition epitope T3, T5, T7 was observed in 76.1%, 100% and 100% of the strains respectively.ConclusionStrains of HEV genotype 1a are dominant in Bangladesh and are associated with endemic and outbreak of HEV infection. HEV isolates in Bangladesh have high prevalence of virulence associated mutations and mutation which alters antigenicity to B and T cell epitopes.
| S-EPMC8297744 | biostudies-literature
Project description:An outbreak of hepatitis E virus occurred in an outdoor monkey breeding facility in Japan during 2004-2006. Phylogenetic analysis indicated that this virus was genotype 3. This virus was experimentally transmitted to a cynomolgus monkey. Precautions should be taken by facility personnel who work with monkeys to prevent infection.
| S-EPMC3557886 | biostudies-literature
Project description:During 2011, 5 persons in the area of Lazio, Italy were infected with a monophyletic strain of hepatitis E virus that showed high sequence homology with isolates from swine in China. Detection of this genotype in Italy parallels findings in other countries in Europe, signaling the possible spread of strains new to Western countries.
| S-EPMC3558000 | biostudies-literature