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1.
J Viral Hepat ; 30(1): 19-28, 2023 01.
Article in English | MEDLINE | ID: mdl-36201354

ABSTRACT

ATI-2173 is an active site polymerase inhibitor nucleotide in development as part of a potentially curative regimen for chronic hepatitis B virus (HBV) infection. This study evaluated the safety, tolerability, pharmacokinetics (PK) and antiviral activity of ATI-2173. This was a phase 1b, randomized, double-blind, placebo-controlled trial in treatment-naive adults with chronic HBV infection conducted in the Republic of Moldova and Ukraine (ClinicalTrials.gov: NCT04248426). Patients positive for hepatitis B surface antigen were randomized 6:2 to receive once-daily oral doses of ATI-2173 10, 25, or 50 mg (n = 6 per dose) or placebo (n = 7) for 28 days, with off-treatment monitoring for 24 weeks. Endpoints included PK parameters of ATI-2173 and its metabolite clevudine, maximum reduction from baseline in HBV DNA, and safety and tolerability. Treatment-emergent adverse events occurred in eight patients (47%) receiving ATI-2173 and five (71%) receiving placebo; headache was the most common (n = 4). ATI-2173 PK was generally dose proportional. Systemic clevudine exposure with ATI-2173 dosing was substantially reduced compared with historical values observed with clevudine administration. On Day 28, mean changes from baseline in HBV DNA were -2.72 to -2.78 log10  IU/ml with ATI-2173 and +0.17 log10  IU/ml with placebo. Off-treatment sustained viral suppression and decreases in covalently closed circular DNA biomarkers were observed in most patients; one maintained undetectable HBV DNA at 24 weeks off treatment. In this 28-day monotherapy study, ATI-2173 demonstrated safety and antiviral activity, with sustained off-treatment effects and substantially reduced systemic clevudine exposure. These results support evaluation of ATI-2173 with tenofovir disoproxil fumarate in phase 2 studies.


Subject(s)
Hepatitis B, Chronic , Adult , Humans , Nucleotides/therapeutic use , DNA, Viral , Catalytic Domain , Hepatitis B e Antigens , Antiviral Agents/adverse effects , Hepatitis B virus/genetics
2.
Article in English | MEDLINE | ID: mdl-32540975

ABSTRACT

ATI-2173 is a novel liver-targeted molecule designed to deliver the 5'-monophosphate of clevudine for the treatment of chronic hepatitis B infection. Unlike other nucleos(t)ides, the active clevudine-5'-triphosphate is a noncompetitive, non-chain-terminating inhibitor of hepatitis B virus (HBV) polymerase that delivers prolonged reduction of viremia in both a woodchuck HBV model and in humans for up to 6 months after cessation of treatment. However, long-term clevudine treatment was found to exhibit reversible skeletal myopathy in a small subset of patients and was subsequently discontinued from development. ATI-2173 was designed by modifying clevudine with a 5'-phosphoramidate to deliver the 5'-monophosphate to the liver. Bypassing the first phosphorylation step of clevudine, the 5'-monophosphate is converted to the active 5'-triphosphate in the liver. ATI-2173 is a selective inhibitor of HBV with an anti-HBV 50% effective concentration (EC50) of 1.31 nM in primary human hepatocytes, with minimal to no toxicity in hepatocytes, skeletal muscle, liver, kidney, bone marrow, and cardiomyocytes. ATI-2173 activity was decreased by viral polymerase mutations associated with entecavir, lamivudine, and adefovir resistance, but not capsid inhibitor resistance mutations. A single oral dose of ATI-2173 demonstrated 82% hepatic extraction, no food effect, and greatly reduced peripheral exposure of clevudine compared with equimolar oral dosing of clevudine. Despite reduced plasma clevudine exposure, liver concentrations of the 5'-triphosphate were equivalent following ATI-2173 versus clevudine administration. By selectively delivering the 5'-monophosphate to the liver, while retaining the unique anti-HBV activity of the 5'-triphosphate, ATI-2173 may provide an improved pharmacokinetic profile for clinical use, reducing systemic exposure of clevudine and potentially eliminating skeletal myopathy.


Subject(s)
Hepatitis B, Chronic , Hepatitis B , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Hepatitis B/drug therapy , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Nucleotides/therapeutic use
3.
Article in English | MEDLINE | ID: mdl-29180528

ABSTRACT

There is a growing body of evidence suggesting that some ribonucleoside/ribonucleotide analogs may be incorporated into mitochondrial RNA by human mitochondrial DNA-dependent RNA polymerase (POLRMT) and disrupt mitochondrial RNA synthesis. An assessment of the incorporation efficiency of a ribonucleotide analog 5'-triphosphate by POLRMT may be used to evaluate the potential mitochondrial toxicity of the analog early in the development process. In this report, we provide a simple method to prepare active recombinant POLRMT. A robust in vitro nonradioactive primer extension assay was developed to assay the incorporation efficiency of ribonucleotide analog 5'-triphosphates. Our results show that many ribonucleotide analogs, including some antiviral compounds currently in various preclinical or clinical development stages, can be incorporated into newly synthesized RNA by POLRMT and that the incorporation of some of them can lead to chain termination. The discrimination (D) values of ribonucleotide analog 5'-triphosphates over those of natural ribonucleotide triphosphates (rNTPs) were measured to evaluate the incorporation efficiency of the ribonucleotide analog 5'-triphosphates by POLRMT. The discrimination values of natural rNTPs under the condition of misincorporation by POLRMT were used as a reference to evaluate the potential mitochondrial toxicity of ribonucleotide analogs. We propose the following criteria for the potential mitochondrial toxicity of ribonucleotide analogs based on D values: a safe compound has a D value of >105; a potentially toxic compound has a D value of >104 but <105; and a toxic compound has a D value of <104 This report provides a simple screening method that should assist investigators in designing ribonucleoside-based drugs having lower mitochondrial toxicity.


Subject(s)
DNA-Directed RNA Polymerases/genetics , Mitochondria/genetics , Polyphosphates/pharmacology , RNA/drug effects , Ribonucleosides/genetics , Ribonucleotides/pharmacology , Antiviral Agents/pharmacology , Humans , Mitochondria/drug effects , RNA/genetics
4.
Article in English | MEDLINE | ID: mdl-27993851

ABSTRACT

Zika virus (ZIKV) is an emerging human pathogen that is spreading rapidly through the Americas and has been linked to the development of microcephaly and to a dramatically increased number of Guillain-Barré syndrome cases. Currently, no vaccine or therapeutic options for the prevention or treatment of ZIKV infections exist. In the study described in this report, we expressed, purified, and characterized full-length nonstructural protein 5 (NS5) and the NS5 polymerase domain (NS5pol) of ZIKV RNA-dependent RNA polymerase. Using purified NS5, we developed an in vitro nonradioactive primer extension assay employing a fluorescently labeled primer-template pair. Both purified NS5 and NS5pol can carry out in vitro RNA-dependent RNA synthesis in this assay. Our results show that Mn2+ is required for enzymatic activity, while Mg2+ is not. We found that ZIKV NS5 can utilize single-stranded DNA but not double-stranded DNA as a template or a primer to synthesize RNA. The assay was used to compare the efficiency of incorporation of analog 5'-triphosphates by the ZIKV polymerase and to calculate their discrimination versus that of natural ribonucleotide triphosphates (rNTPs). The 50% inhibitory concentrations for analog rNTPs were determined in an alternative nonradioactive coupled-enzyme assay. We determined that, in general, 2'-C-methyl- and 2'-C-ethynyl-substituted analog 5'-triphosphates were efficiently incorporated by the ZIKV polymerase and were also efficient chain terminators. Derivatives of these molecules may serve as potential antiviral compounds to be developed to combat ZIKV infection. This report provides the first characterization of ZIKV polymerase and demonstrates the utility of in vitro polymerase assays in the identification of potential ZIKV inhibitors.


Subject(s)
Antiviral Agents/pharmacology , Biological Assay , RNA-Dependent RNA Polymerase/antagonists & inhibitors , Ribonucleotides/pharmacology , Viral Nonstructural Proteins/antagonists & inhibitors , Virus Replication/drug effects , Zika Virus/drug effects , Antiviral Agents/metabolism , Base Sequence , Cations, Divalent , DNA Primers/chemical synthesis , DNA Primers/metabolism , DNA, Single-Stranded/genetics , DNA, Single-Stranded/metabolism , Manganese/metabolism , Polyphosphates/metabolism , Protein Domains , RNA, Viral/antagonists & inhibitors , RNA, Viral/biosynthesis , RNA, Viral/genetics , RNA-Dependent RNA Polymerase/genetics , RNA-Dependent RNA Polymerase/metabolism , Ribonucleotides/metabolism , Staining and Labeling/methods , Viral Nonstructural Proteins/genetics , Viral Nonstructural Proteins/metabolism , Zika Virus/genetics , Zika Virus/metabolism
5.
Antiviral Res ; 209: 105453, 2023 01.
Article in English | MEDLINE | ID: mdl-36379378

ABSTRACT

The unprecedented magnitude of the 2013-2016 Ebola virus (EBOV) epidemic in West Africa resulted in over 11 000 deaths and spurred an international public health emergency. A second outbreak in 2018-2020 in DRC resulted in an additional >3400 cases and nearly 2300 deaths (WHO, 2020). These large outbreaks across geographically diverse regions highlight the need for the development of effective oral therapeutic agents that can be easily distributed for self-administration to populations with active disease or at risk of infection. Herein, we report the in vivo efficacy of N4-hydroxycytidine (EIDD-1931), a broadly active ribonucleoside analog and the active metabolite of the prodrug EIDD-2801 (molnupiravir), in murine models of lethal EBOV infection. Twice daily oral dosing with EIDD-1931 at 200 mg/kg for 7 days, initiated either with a prophylactic dose 2 h before infection, or as therapeutic treatment starting 6 h post-infection, resulted in 92-100% survival of mice challenged with lethal doses of EBOV, reduced clinical signs of Ebola virus disease (EVD), reduced serum virus titers, and facilitated weight loss recovery. These results support further investigation of molnupiravir as a potential therapeutic or prophylactic treatment for EVD.


Subject(s)
Ebolavirus , Hemorrhagic Fever, Ebola , Ribonucleosides , Animals , Mice , Hemorrhagic Fever, Ebola/drug therapy , Hemorrhagic Fever, Ebola/prevention & control , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Ribonucleosides/pharmacology
6.
J Infect Dis ; 202(10): 1510-9, 2010 Nov 15.
Article in English | MEDLINE | ID: mdl-20942646

ABSTRACT

INTRODUCTION: RG7128 (prodrug of PSI-6130) shows potent antiviral efficacy in patients infected with hepatitis C virus (HCV) genotypes 1, 2, or 3, with mean viral load decreases of 2.7 and 5 log(10) IU/mL, respectively, associated with 1500-mg doses twice daily after monotherapy for 2 weeks and with 1000-mg and 1500-mg doses twice daily after treatment in combination with the standard of care (SOC) for 4 weeks. RESULTS: From 32 patients treated with RG7128 monotherapy for 2 weeks, marginal viral load rebound was observed in 3 HCV genotype 1-infected patients, whereas partial response was observed in 2 genotype 1-infected patients. From 85 patients receiving RG7128 in combination with SOC, 1 HCV genotype 1-infected patient experienced a viral rebound, and 2 genotype 3-infected patients experienced a transient rebound. Five genotype 1-infected patients had an HCV load of >1000 IU/mL at the end of 4-week treatment. No viral resistance was observed, per NS5B sequencing and phenotypic studies. PSI-6130 resistance substitution S282T needs to be present at levels of ≥90% within a patient's quasispecies to confer low-level resistance. No evidence of S282T was found by population or clonal sequence analyses. CONCLUSIONS: The requirement for a predominant S282T mutant quasispecies, its low replication capacity, and the low-level resistance it confers probably contribute to the lack of RG7128 resistance observed in HCV-infected patients.


Subject(s)
Antiviral Agents/therapeutic use , Deoxycytidine/analogs & derivatives , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Amino Acid Substitution , Antiviral Agents/pharmacology , Deoxycytidine/pharmacology , Deoxycytidine/therapeutic use , Drug Resistance, Viral/genetics , Drug Therapy, Combination , Hepacivirus/genetics , Hepacivirus/physiology , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , New Zealand , Recombinant Proteins , Selection, Genetic , United States , Viral Load , Viral Nonstructural Proteins/genetics , Virus Replication/drug effects
7.
AIDS ; 16(4): 537-42, 2002 Mar 08.
Article in English | MEDLINE | ID: mdl-11872996

ABSTRACT

OBJECTIVE: In this study we evaluated the possibility that plasma viral load elevations secondary to influenza vaccination in HIV-1-seropositive individuals with previously undetectable viral loads (< 200 copies/ml) could develop resistance-bearing mutations in the viral reverse transcriptase (RT) and protease regions. METHODS: Thirty-four patients with undetectable viral burdens on highly active antiretroviral therapy (HAART) were evaluated for elevations in plasma viral load 2 and 4 weeks post-influenza vaccination. Plasma from patients whose viral load increased after vaccination was subject to genotypic resistance analysis by the line probe assay (LiPA) to determine whether primary resistance-bearing mutations developed during this period and at follow-up. Stored plasma was used to evaluate whether RT or protease mutations existed pre-vaccination. RESULTS: Seven out of 34 patients were found to experience elevations in their viral load after influenza vaccination. Two of the patients revealed evidence of primary RT or protease mutations not demonstrated in earlier pre-vaccination samples. One patient failed therapy after vaccination, and one patient revealed post-vaccination viral load elevations that eventually led to the progressive development of primary zidovudine mutations. CONCLUSION: Evidence is presented that supports the contention that a small subset of patients who experience viral load elevations after influenza vaccination can develop mutational changes in the RT region of the viral genome either acutely or after a failure of the viral load to return to undetectable levels.


Subject(s)
HIV Infections/virology , HIV-1/genetics , Influenza Vaccines/immunology , RNA, Viral , Viral Load , Adult , Aged , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Drug Resistance, Viral/genetics , Female , Genotype , HIV Infections/drug therapy , HIV Infections/immunology , HIV Protease Inhibitors/therapeutic use , Humans , Male , Middle Aged , RNA, Viral/blood , Reverse Transcriptase Inhibitors/therapeutic use
8.
Clin Exp Metastasis ; 19(1): 35-42, 2002.
Article in English | MEDLINE | ID: mdl-11918081

ABSTRACT

We hypothesize that elevation of nm23-HI metastasis suppressor gene expression in micrometastatic tumor cells may reduce their subsequent colonization and invasion, and induce differentiation, with a clinical benefit. This report presents the first analysis of the nm23-HI promoter to identify sites which can increase its transcription. Deletion mapping of a 2.1 kb nm23-H1 promoter fragment tethered to a reporter gene identified three regions involved in its differential expression levels among a panel of human breast carcinoma cell lines: a 195 bp NheI-XbaI fragment responsible for basal expression levels, a 248 bp AvrII-Nhel fragment which contributed to the elevated nm23-H1 expression observed in the high expressing cell lines, and a 544 bp AvrII fragment containing an inhibitory element. Examination of the 248 bp AvrII-NheI fragment revealed the unexpected presence of three transcription factor binding sites (MAF/Ets, CTF/NF1 half site and ACAAAG enhancer) previously identified in the MMTV-LTR, and in WAP and milk gene promoters, proposed to mediate mammary-specific gene expression. Mutation of the three sites, individually or together, resulted in two-fold reductions in reporter gene expression. As controls, the same panel of mutations caused a different pattern of reporter gene expression in a non-mammary cell line, and mutation of another nearby site was without effect on nm23-HI. Our data identify a complex regulatory pattern for nm23-H1 transcription, and suggest that a mammary-specific cassette of transcription factors contribute to its elevated expression


Subject(s)
Breast Neoplasms/pathology , Carcinoma/pathology , DNA, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Mammary Tumor Virus, Mouse/genetics , Monomeric GTP-Binding Proteins/biosynthesis , Neoplasm Metastasis/genetics , Neoplasm Proteins/biosynthesis , Nucleoside-Diphosphate Kinase , Promoter Regions, Genetic/genetics , Terminal Repeat Sequences/genetics , Transcription Factors/biosynthesis , Transcription Factors/metabolism , Binding Sites , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , CCAAT-Enhancer-Binding Proteins/metabolism , Carcinoma/genetics , Carcinoma/metabolism , Consensus Sequence , Electrophoretic Mobility Shift Assay , Enhancer Elements, Genetic/genetics , Female , Genes, Reporter , Humans , Monomeric GTP-Binding Proteins/genetics , Mutagenesis , NFI Transcription Factors , NM23 Nucleoside Diphosphate Kinases , Neoplasm Proteins/genetics , Organ Specificity , Polymorphism, Restriction Fragment Length , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-ets , Recombinant Fusion Proteins/biosynthesis , Sequence Deletion , Transcription Factors/genetics , Transcription, Genetic , Tumor Cells, Cultured
9.
Antivir Ther ; 9(4): 529-36, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15456084

ABSTRACT

Reverset (2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine, RVT) is a potent inhibitor of HIV-1 replication in cell culture, with a 90% effective concentration at or below 1 microM. In vitro, RVT retains its activity against isolates harbouring mutations in the reverse transcriptase (RT) gene that otherwise confer resistance to lamivudine and/or zidovudine. The pharmacokinetics and safety of single oral doses of RVT (10-200 mg) were evaluated in an initial Phase I clinical trial. The viral load changes were determined on 18 HIV-1-infected antiretroviral therapy-naive subjects that were randomized into three cohorts, each cohort consisting of three study periods. The subjects received up to two oral doses of active drug and one placebo dose with a 1-week washout period separating the three study periods. Quantification of viral RNA was performed on the pre-dose, 12, 24 and 48 h post-dose plasma samples. A single oral dose of RVT to antiretroviral-naive subjects significantly reduced plasma viral load by 0.45 +/- 0.10 log10 copies/ml (P=0.0003). A mean drop of 0.37 +/- 0.12 log10 copies/ml (P=0.001) was obtained at the lowest dose of 10 mg. Sequence analysis of the HIV-1 RT gene performed before and after RVT dosing detected no genotypic changes in this short-term study. The viral RT gene of one subject had at predose the following genotype: L41 + N103 + C181 + W210 + D215, indicating prior exposure to zidovudine and non-nucleoside analogues, and anticipating high-level resistance against these agents. A single 10 mg RVT dose resulted in a viral load drop of 0.61 +/- 0.05 log10 providing evidence that a viral strain with the indicated genotype is susceptible to RVT.


Subject(s)
Cytidine Triphosphate/analogs & derivatives , Cytidine Triphosphate/therapeutic use , HIV Infections/drug therapy , HIV Reverse Transcriptase/antagonists & inhibitors , HIV-1/isolation & purification , Reverse Transcriptase Inhibitors/therapeutic use , Administration, Oral , Adolescent , Adult , Cohort Studies , Cytidine Triphosphate/administration & dosage , Cytidine Triphosphate/pharmacokinetics , Dose-Response Relationship, Drug , Drug Administration Schedule , Genotype , HIV Infections/metabolism , HIV Infections/virology , HIV Reverse Transcriptase/genetics , HIV-1/genetics , Humans , Middle Aged , Reverse Transcriptase Inhibitors/pharmacokinetics , Sequence Analysis, RNA , Viral Load , Zalcitabine/analogs & derivatives
10.
Rev Soc Bras Med Trop ; 42(3): 239-44, 2009.
Article in English | MEDLINE | ID: mdl-19684968

ABSTRACT

The role of sexual or intrafamilial transmission of hepatitis C is controversial. A phylogenetic analysis was performed on the non-structural region 5B of the hepatitis C virus (NS5B-HCV). High percentages of homology (mean of 98.3%) were shown between the couples. Twenty (83.3%) of the 24 men but only two of the women (8.3%) reported having had sexually transmitted diseases during their lives. The risk factors for HCV acquisition were blood transfusion (10 couples), use of illegal injected drugs (17), use of inhalants (15), acupuncture (5) and tattoos (5). The shared use of personal hygiene items included toothbrushes between six couples (25%), razor blades between 16 (66.7%), nail clippers between 21 (87.5%) and manicure pliers between 14 (58.3%). The high degree of similarity of the hepatitis C virus genome supports the hypothesis of hepatitis C virus transmission between these couples. The shared use of personal hygiene items suggests the possibility of intrafamilial transmission of infection.


Subject(s)
Hepacivirus/genetics , Hepatitis C/transmission , Spouses , Viral Nonstructural Proteins/genetics , Adult , Aged , Female , Genotype , Hepatitis C/virology , Humans , Male , Middle Aged , Phylogeny , Risk Factors
11.
Braz. j. infect. dis ; 14(5): 427-432, Sept.-Oct. 2010. ilus, tab
Article in English | LILACS | ID: lil-570554

ABSTRACT

INTRODUCTION: There is general consensus that hepatitis C virus is efficiently transmitted by the parenteral route, whereas data on viral transmission by sexual or non-sexual intrafamilial contact are conflicting. OBJECTIVE AND METHOD: The aim of this study was to investigate the transmission of hepatitis C virus in nine heterosexual couples. RESULT: The mean age of the couples was 43.7 years. When interviewed, all of the women denied the presence of risk factors for acquisition of the infection, whereas the cause of infection in the nine husbands could be attributed to blood transfusions in two of them (22.2 percent), use of intravenous and inhaled drugs in six (66.7 percent), acupuncture in one (11.1 percent), and tattooing in one (11.1 percent). All men and none of the women reported sexual relations with sex professionals. The mean homology score (Non Structural 5b-hepatitis C virus) was 98.4 percent. Among the nine couples with matching subtypes, one (11.1 percent) was infected with subtype 1a, three (33.3 percent) with subtype 1b, and five (55.5 percent) with subtype 3a. Shared personal hygiene items showed a much higher correlation with the possible route of transmission and were better supported by the sequence homology data than the other associated risk factors. Three (33.3 percent) couples shared toothbrushes, seven (77.8 percent) shared razor blades, eight (88.8 percent) shared nail clippers, and six (66.7 percent) shared manicure cutters. CONCLUSION: Sharing of personal hygiene items was a confounding factor in the discussion of sexual hepatitis C virus transmission and the hypothesis of male-to-female transmission was supported in this study.


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Hepacivirus/genetics , Hepatitis C/transmission , Sexual Partners , Sexually Transmitted Diseases, Viral/transmission , Spouses/statistics & numerical data , Brazil/epidemiology , Genotype , Hepatitis C/epidemiology , Phylogeny , Risk Factors , RNA, Viral/blood , Sexually Transmitted Diseases, Viral/epidemiology
12.
Rev. Soc. Bras. Med. Trop ; 42(3): 239-244, May-June 2009. ilus, tab
Article in English | LILACS | ID: lil-522249

ABSTRACT

The role of sexual or intrafamilial transmission of hepatitis C is controversial. A phylogenetic analysis was performed on the non-structural region 5B of the hepatitis C virus (NS5B-HCV). High percentages of homology (mean of 98.3 percent) were shown between the couples. Twenty (83.3 percent) of the 24 men but only two of the women (8.3 percent) reported having had sexually transmitted diseases during their lives. The risk factors for HCV acquisition were blood transfusion (10 couples), use of illegal injected drugs (17), use of inhalants (15), acupuncture (5) and tattoos (5). The shared use of personal hygiene items included toothbrushes between six couples (25 percent), razor blades between 16 (66.7 percent), nail clippers between 21 (87.5 percent) and manicure pliers between 14 (58.3 percent). The high degree of similarity of the hepatitis C virus genome supports the hypothesis of hepatitis C virus transmission between these couples. The shared use of personal hygiene items suggests the possibility of intrafamilial transmission of infection.


O papel da transmissão sexual ou intrafamiliar da hepatite C é controverso. Foi feita análise filogenética, região não estrutural 5B do vírus da hepatite C (NS5B-HCV). Altas percentagens de homologia com média de 98,3 por cento foi revelada entre os casais. Vinte (83,3 por cento) de 24 homens, contra apenas duas (8,3 por cento) mulheres reportaram doença sexualmente transmisível durante suas vidas. Os fatores de risco para aquisição da doença foram: transfusão de sangue para 10 casais, uso de drogas ilícitas injetáveis para 17, inalatórias para 15, acupuntura em 5 e tatuagens para 5. O compartilhamento de utensílios de higiene pessoal incluem: escova de dente para seis (25 por cento) dos casais, lâmina de barbear para 16 (66,7 por cento), cortador de unhas para 21 (87,5 por cento) e alicate de manicure para 14 (58,3 por cento). O alto grau de similaridade genômica entre os vírus da hepatite C suporta a hipótese de transmissão entre os casais. O uso compartilhado de utensílios de higiene pessoal sugere a possibilidade de transmissão intrafamiliar.


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Hepacivirus/genetics , Hepatitis C/transmission , Spouses , Viral Nonstructural Proteins/genetics , Genotype , Hepatitis C/virology , Phylogeny , Risk Factors
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