Resistance to antiretroviral therapy (ART) threatens the success of programs to reduce HIV morbidity and mortality, particularly in countries with few treatment options. In the present study, genotype and phenotype data from ART-naïve and experienced hospitalized patients infected with HIV in Tehran, Iran were used to assess the prevalence and types of transmitted (TDR) and acquired drug resistance (ADR) mutations. All 30 participants naïve to ART and 62 of 70 (88.6%) participants receiving ART had detectable viral loads. Among participants receiving ART with sequencing data available (n = 62), 36 (58.1%) had at least one drug resistance mutation; the most common mutations were K103N (21.0%), M184V (19.4%), and the thymidine analogue mutations. Seven (11.3%), 27 (43.5%), and two (3.2%) of these participants had resistance to one, two, and three drug classes, respectively. High-level resistance to efavirenz (EFV) was more common among participants on EFV-based regimens than high-level lopinavir/ritonivar (LPV/r) resistance among those on LPV/r-based regimens (55.3% vs. 6.7%, P < 0.0001). Two (6.7%) antiretroviral-naïve participants had K103N mutations. These findings document an alarmingly high frequency of multiple HIV drug class resistance in Iran, confirm the presence of TDR, and highlight the need for systematic viral load monitoring and drug resistance testing, including at diagnosis. Expanded access to new antiretroviral medications from additional drug classes is needed.
BackgroundTorque teno virus (TTV) was the first human Circoviridae detected in a Japanese patient with unknown hepatitis in 1997. Subsequently, several studies performed to evaluate different aspects of Torque teno virus pathogenesis.ObjectivesThe present study aimed to determine dominant genotype of Torque teno virus in chronic hepatitis disease using 5΄-UTR sequence among patients infected by hepatitis C virus in Shiraz – Iran.Patients and MethodsThe study conducted in 240 patients with chronic hepatitis C from Prof. Alborzi Clinical Microbiology Research Center. The presence of Torque teno virus DNA and its genotype in plasma was assessed by nested polymerase chain reaction using two primer sets for 5΄-UTR and N22 regions. Phylogenetic analysis was performed based on 5΄-UTR region.ResultsDNA of Torque teno virus was detected in 220 out of 240 (92 %) patients with chronic hepatitis C by the use of 5΄-UTR primer based PCR method and in 12 out of 240 (5%) by the use of N22 primer. Based on phylogenetic analysis it was shown that the Dominant genotype in this study was 11. Genotypes 1, 3, 17, and 22 were also detected. Some sequences could not be classified to a specific genotype.ConclusionsThe prevalence of Torque teno virus DNA in patients with chronic hepatitis C disease by the use of 5΄-UTR primer appeared to be higher compared to that revealed by N22 primer. We observed five genotypes among hepatitis C chronic patients in our study.
BackgroundOccult hepatitis B infection (OBI) has been described in various clinical settings including after hepatitis B virus (HBV) immunization. The purpose of study was to characterize the prevalence of OBI among immunized children from a subset of general population and the parents of OBI‐positive cases.MethodsSera of 1200 children from general population who have been previously immunized by HBV vaccine were assayed for anti‐HBs. 660 were randomly selected for HBV DNA testing by different polymerase chain reaction (PCR) methods and were analysed by direct sequencing on surface genes.ResultsNone of participants were positive for HBsAg and anti‐HBc. 549 (45.7%) and 651 (54.3%) cases had anti‐HBs > 10 mIU/mL (responders) and < 10 mIU/mL (nonresponders) respectively. Of 660 selected specimens, 91 (16%) of children were positive for OBI. 23 (25.2%) and 68 (74.8%) of HBV DNA positive cases were belonged to responders and nonresponders, respectively, showing significant difference (P < .001). The mean levels of anti‐HBs in OBI‐positive and OBI‐negative groups, showed no considerable variations. The mean viral load for OBI‐positive cases showed substantial differences between responders and nonresponders (P = .007). Of 49 parents (98 individuals) of OBI‐positive children 11 (22%) and 18 (36%) were positive for anti‐HBc and anti‐HBs respectively. Molecular testing was positive in 32 subjects (16 couples, 32.6%). In total, 6 mothers and 11 fathers were positive for OBI.ConclusionA proportion of OBI‐positive vaccinated children could be existed in different populations. This finding could be arisen from vertical HBV transmission or vertical OBI possibly from their parents.
Backgroundchronic hepatitis B virus (HBV) infection is a multifactorial disease that can result in serious clinical complications. Host genetic background especially the genes that encode immunologic factors like INF-γ and its receptor (IFN-γ R) are critical in the pathogenesis of infection.ObjectivesThe current study aimed to investigate the association between two single nucleotide polymorphisms (SNPs) at positions -611 and -56 within the promoter region of gamma interferon receptor1 gene (IFN-γ R1) and chronic HBV infection.Materials and MethodsGenomic DNA from peripheral blood samples of 200 chronically HBV infected patients and 200 healthy blood donors, as controls, were collected and genomic DNA was extracted by phenol-chloroform method and DNA analysis genotype identification was performed by PCR-RFLP.ResultsThe results indicated that both SNP’s frequency had a significant difference in the patient and control groups. At position -56, TT genotype was associated with patient group and P value was 0.002 and at position -611, GG genotype was further observed in control group and P value was 0.006.ConclusionsPresence of G allele at position -611 within promoter of IFN-γ R1 gene in the enrolled population for the study was related to lower risk of disease, and presence of T allele at position -56 was also related to susceptibility to chronic HBV infection. Men had higher frequency of chronic HBV infection, which might be the result of high risk behavior.
Summary. -The various roles of hepatitis C virus (HCV) NS3 protein in viral pathogenesis are emphasized, especially in the progression of fibrosis and tumors. The levels of miR-122 have been widely accepted as a critical factor in viral pathogenesis and disease progression. However, the possible correlation between miR-122 levels and fibrosis state has been less investigated. Therefore, in this study, plasmids expressing protease competent and protease mutated non-structural proteins 3 (NS3) were transfected into LX-2 cell line. Subsequently, the total RNA was extracted and real-time PCR was performed to measure the expression level of miR-122, collagen type 1 alpha 1 (COL1A1), alpha smooth muscle actin (α-SMA), and tissue inhibitor of metaloproteinase 1 (TIMP-1). Moreover, the transforming growth factor beta (TGF-β) levels in the supernatants of transfected cells were evaluated by ELISA. The gene expression analysis of fibrotic genes and TGF-β cytokine in LX-2 cells showed that protease competent NS3 had a significant fibrogenic impact when compared to protease defective NS3 or GFP control plasmids (P <0.001). The results also demonstrated that the expression of miR-122 was downregulated in both versions of the cells transfected with NS3 plasmids (P <0.01) irrespective of protease function. These results suggested that the protease function of NS3 protein is a crucial factor for the induction of hepatic fibrosis but it doesn't play a complete role in the expression of miR-122.Keywords: HCV; miRNA; fibrosis; HSCs; NS3; protease; miR-122 * Corresponding author. E-mail: ravanshad@modares.ac.ir; phone: +98-2182883836. Abbreviations: COL1A1 = collagen type 1 alpha 1; HCC = hepatocellular carcinoma; HCV = hepatitis C virus; HSCs = hepatic stellate cells; NS3 = non-structural protein 3; α-SMA = alpha smooth muscle actin; TGF-β = transforming growth factor beta; TIMP-1 = tissue inhibitor of metaloproteinase 1
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