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1.
BMC Infect Dis ; 20(1): 839, 2020 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-33183254

RESUMEN

BACKGROUND: Hepatitis B virus (HBV) infection is a public health problem in Togo and transmission to the child occurs mainly during childbirth. The objective of this study was to estimate the prevalence of HBV among childbearing women and infants born to HBV positive mothers in Togo. METHODS: A national cross-sectional study was carried out in six cities in Togo in the six health regions in Togo. Mother-child pairs were recruited from immunization centers or pediatric wards in Lomé, Tsévié, Atakpamé, Sokodé, Kara and Dapaong in 2017. Women aged 18 and over with one child of at least 6 months old were included. A standardized questionnaire was used for data collection and HBV screening was performed using Determine® rapid tests. The prevalence of HBV, defined by a positive HBV surface antigen (HBsAg), was estimated in mothers and then in infants of mothers who were positive for HBsAg. Logistic regression model was performed to identify risk factors for HBsAg positivity in mothers. RESULTS: A total of 2105 mothers-pairs child were recruited. The median age of mothers and infants was 29 years, interquartile range (IQR) [25-33] and 2.1 years, IQR [1-3] respectively. About 35% of women were screened for HBV during antenatal care and 85% of infants received three doses of HBV immunization. Among mothers, the prevalence of HBV was 10.6, 95% confidence interval (95% CI) [9.4-12.0%], and 177 had detectable HBV viral load (> 10 IU/mL). Among mothers with positive HBsAg, three infants also had positive HBsAg, a prevalence of 1.3, 95% CI [0.2-3.8%]. In multivariable analysis, HIV-infection (aOR = 2.19; p = 0.018), having at least three pregnancies (aOR = 1.46; p = 0.025) and living in Tsévié (aOR = 0.31; p < 0.001) compared to those living in Lomé, were associated to HBV infection in mothers. CONCLUSION: In this study, one out of 10 childbearing women were infected with HBV, but less than 2% of infant born to HBV positive mothers under 5 years' old who received immunization under the Expanded Program on Immunization were infected. Improving antenatal screening and providing targeted interventions in babies could help eliminate HBV in Togo.


Asunto(s)
Virus de la Hepatitis B/inmunología , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/prevención & control , Vacunación , Adulto , Preescolar , Estudios Transversales , Femenino , VIH , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/virología , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/genética , Humanos , Lactante , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Atención Prenatal , Prevalencia , Togo/epidemiología , Adulto Joven
2.
J Clin Virol ; 132: 104618, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32919222

RESUMEN

The aim of this study was to assess the analytical performances, sensitivity and specificity, of two rapid tests (Covid- Presto® test rapid Covid-19 IgG/IgM and NG-Test® IgM-IgG COVID-19) and one automated immunoassay (Abbott SARS-CoV-2 IgG) for detecting anti- SARS-CoV-2 antibodies. This study was performed with: (i) a positive panel constituted of 88 SARS-CoV-2 specimens collected from patients with a positive SARS-CoV-2 RT-PCR, and (ii) a negative panel of 120 serum samples, all collected before November 2019, including 64 samples with a cross-reactivity panel. Sensitivity of Covid-Presto® test for IgM and IgG was 78.4% and 92.0%, respectively. Sensitivity of NG-Test® for IgM and IgG was 96.6% and 94.9%, respectively. Sensitivity of Abbott IgG assay was 96.5% showing an excellent agreement with the two rapid tests (κ = 0.947 and κ = 0.936 for NGTest ® and Covid-Presto® test, respectively). An excellent agreement was also observed between the two rapid tests (κ = 0.937). Specificity for IgM was 100% and 86.5% for Covid-Presto® test and NG-Test®, respectively. Specificity for IgG was 92.0%, 94.9% and 96.5% for Covid-Presto®, NGTest ®, and Abbott, respectively. Most of the false positive results observed with NG-Test® resulted from samples containing malarial antibodies. In conclusion, performances of these 2 rapid tests are very good and comparable to those obtained with automated immunoassay, except for IgM specificity with the NG-Test®. Thus, isolated IgM should be cautiously interpreted due to the possible false-positive reactions with this test. Finally, before their large use, the rapid tests must be reliably evaluated with adequate and large panel including early seroconversion and possible cross-reactive samples.

3.
J Gastroenterol Hepatol ; 31(10): 1750-1756, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26992056

RESUMEN

BACKGROUND AND AIM: The impact of basal core promoter (BCP) and precore (PC) mutants of the hepatitis B virus (HBV) on liver disease severity remains controversial. The aim of the present study was to screen BCP and PC mutations in 252 HBV surface antigen (HBsAg) positive carriers in France and to assess relationships between these mutations and severe fibrosis. METHODS: Direct sequencing of the precore/core gene was used to detect A1762T/G1764A and G1757A mutations in the BCP and G1896A and G1899A mutations in the PC region. RESULTS: The prevalences of A1762T/G1764A, G1757A, G1896A, and G1899A mutations were 34.1%, 38.7%, 54.9%, and 29.3% (P < 0.001), respectively. The independent predictors of severe fibrosis (≥F3 Metavir) were older age (P < 0.001), male gender (P = 0.012), elevated alanine aminotransferase (P < 0.001), and the double A1762T/G1764A mutant with no other mutations (P = 0.011). Interestingly, the association of the G1899A mutation with the double A1762T/G1764A mutant significantly counteracted the deleterious effect of the sole double A1762T/G1764A mutant (odds ratio [OR] = 0.28 vs. OR = 3.55, respectively, P = 0.028). CONCLUSIONS: Patients with the A1762T/G1764A mutation have a higher risk of severe fibrosis. The G1899A mutation is a protective factor against severe fibrosis that counteracted the deleterious effect of the A1762T/G1764A mutation. Finally, host phenotypic and HBV genotypic markers independently predict fibrosis severity.


Asunto(s)
Virus de la Hepatitis B/genética , Hepatitis B Crónica/virología , Cirrosis Hepática/virología , Mutación , Adulto , Factores de Edad , Anciano , ADN Viral/análisis , ADN Viral/genética , Femenino , Antígenos de Superficie de la Hepatitis B/genética , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Regiones Promotoras Genéticas/genética , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Virulencia/genética
4.
J Clin Microbiol ; 53(7): 2195-202, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25926499

RESUMEN

The pretherapeutic presence of protease inhibitor (PI) resistance-associated variants (RAVs) has not been shown to be predictive of triple-therapy outcomes in treatment-naive patients. However, they may influence the outcome in patients with less effective pegylated interferon (pegIFN)-ribavirin (RBV) backbones. Using hepatitis C virus (HCV) population sequence analysis, we retrospectively investigated the prevalence of baseline nonstructural 3 (NS3) RAVs in a multicenter cohort of poor IFN-RBV responders (i.e., prior null responders or patients with a viral load decrease of <1 log IU/ml during the pegIFN-RBV lead-in phase). The impact of the presence of these RAVs on the outcome of triple therapy was studied. Among 282 patients, the prevalances (95% confidence intervals) of baseline RAVs ranged from 5.7% (3.3% to 9.0%) to 22.0% (17.3% to 27.3%), depending to the algorithm used. Among mutations conferring a >3-fold shift in 50% inhibitory concentration (IC50) for telaprevir or boceprevir, T54S was the most frequently detected mutation (3.9%), followed by A156T, R155K (0.7%), V36M, and V55A (0.35%). Mutations were more frequently found in patients infected with genotype 1a (7.5 to 23.6%) than 1b (3.3 to 19.8%) (P = 0.03). No other sociodemographic or viroclinical characteristic was significantly associated with a higher prevalence of RAVs. No obvious effect of baseline RAVs on viral load was observed. In this cohort of poor responders to IFN-RBV, no link was found with a sustained virological response to triple therapy, regardless of the algorithm used for the detection of mutations. Based on a cross-study comparison, baseline RAVs are not more frequent in poor IFN-RBV responders than in treatment-naive patients and, even in these difficult-to-treat patients, this study demonstrates no impact on treatment outcome, arguing against resistance analysis prior to treatment.


Asunto(s)
Antivirales/farmacología , Farmacorresistencia Viral , Hepacivirus/efectos de los fármacos , Hepatitis C Crónica/virología , Inhibidores de Proteasas/farmacología , Adulto , Anciano , Antivirales/uso terapéutico , Femenino , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Concentración 50 Inhibidora , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Mutación Missense , Oligopéptidos/farmacología , Oligopéptidos/uso terapéutico , Prolina/análogos & derivados , Prolina/farmacología , Prolina/uso terapéutico , Inhibidores de Proteasas/uso terapéutico , Estudios Retrospectivos , Ribavirina/uso terapéutico , Resultado del Tratamiento , Proteínas no Estructurales Virales/genética
5.
Clin Res Hepatol Gastroenterol ; 38(5): 570-6, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25130796

RESUMEN

BACKGROUND AND AIMS: There is evidence for an association between thrombosis in the hepatic microcirculation and liver fibrosis. The aim of this study was to evaluate the role of daily low-dose aspirin (75 or 100mg, given for prevention of hepatic artery thrombosis) in fibrosis progression to ≥ F2 fibrosis score in liver-transplant recipients with recurrent hepatitis C virus (HCV). METHODS: All HCV-positive patients who had undergone liver transplantation (LT) between 2000 and 2010 were included. Exclusion criteria were negative HCV RNA, previous LT or death within a year of LT. Liver fibrosis was assessed by histological evaluation. Data were censored at the date of the last histological evaluation before starting anti HCV therapy. Progression to fibrosis F ≥ 2 was analyzed with a multistate model with time-dependent covariables. RESULTS: One hundred and eighty-eight patients were included. In univariate analysis, older recipient and donor age, male donor gender, activity score ≥ A2 after LT, number of steroid boluses and aspirin intake (HR: 0.75 [0.57-0.97]; P=0.03) influenced the risk of progression to fibrosis ≥ F2. In multivariate analysis, adjusted on site, older donor age, male donor gender, activity score ≥ A2 and number of steroids boluses, remained independent predictors of fibrosis progression, while younger recipient age and aspirin intake (HR: 0.65 [0.47-0.91]; P=0.01) were associated with a slower fibrosis progression. CONCLUSION: Low-dose aspirin treatment might be associated with a lower risk of liver fibrosis progression in patients with HCV recurrence after LT.


Asunto(s)
Aspirina/uso terapéutico , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/etiología , Trasplante de Hígado , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos
6.
J Clin Microbiol ; 51(5): 1428-33, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23426922

RESUMEN

Hepatitis C virus (HCV) protease inhibitor resistance-associated substitutions are selected during triple-therapy breakthrough. This multicenter quality control study evaluated the expertise of 23 French laboratories in HCV protease inhibitor resistance genotyping. A panel of 12 well-defined blinded samples comprising two wild-type HCV strains, nine transcripts from synthetic NS3 mutant samples or from clinical strains, and one HCV RNA-negative sample was provided to the participating laboratories. The results showed that any laboratory with expertise in sequencing techniques should be able to provide reliable HCV protease inhibitor resistance genotyping. Only a 0.7% error rate was reported for the amino acid sites studied. The accuracy of substitution identification ranged from 75% to 100%, depending on the laboratory. Incorrect results were mainly related to the methodology used. The results could be improved by changing the primers and modifying the process in order to avoid cross-contamination. This study underlines the value of quality control programs for viral resistance genotyping, which is required prior to launching observational collaborative multicenter studies on HCV resistance to direct-acting antiviral agents.


Asunto(s)
Antivirales/farmacología , Farmacorresistencia Viral/genética , Hepacivirus/efectos de los fármacos , Hepacivirus/genética , Inhibidores de Proteasas/farmacología , Proteínas no Estructurales Virales/genética , Secuencia de Aminoácidos , Antivirales/química , Secuencia de Bases , Genotipo , Hepacivirus/enzimología , Mutación , Inhibidores de Proteasas/química , Control de Calidad , Análisis de Secuencia de ADN
7.
J Virol ; 84(19): 10139-47, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20631141

RESUMEN

Mutations in the internal ribosome entry site (IRES) of hepatitis A virus (HAV) have been associated with enhanced in vitro replication and viral attenuation in animal models. To address the possible role of IRES variability in clinical presentation, IRES sequences were obtained from HAV isolates associated with benign (n = 8) or severe (n = 4) hepatitis. IRES activity was assessed using a bicistronic dual-luciferase expression system in adenocarcinoma (HeLa) and hepatoma (HuH7) cell lines. Activity was higher in HuH7 than in HeLa cells, except for an infrequently isolated genotype IIA strain. Though globally low, significant variation in IRES-dependent translation efficiency was observed between field isolates, reflecting the low but significant genetic variability of this region (94.2% +/- 0.5% nucleotide identity). No mutation was exclusive of benign or severe hepatitis, and variations in IRES activity were not associated with a clinical phenotype, indirectly supporting the preponderance of host factors in determining the clinical presentation.


Asunto(s)
Regiones no Traducidas 5'/genética , Virus de la Hepatitis A/genética , Virus de la Hepatitis A/patogenicidad , Hepatitis A/virología , ARN Viral/genética , Enfermedad Aguda , Adolescente , Adulto , Secuencia de Bases , Línea Celular , Niño , Cartilla de ADN/genética , ADN Viral/genética , Francia , Variación Genética , Genotipo , Células HeLa , Virus de la Hepatitis A/aislamiento & purificación , Virus de la Hepatitis A/fisiología , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutagénesis Sitio-Dirigida , Mutación , Conformación de Ácido Nucleico , Filogenia , Biosíntesis de Proteínas , ARN Viral/química , Virulencia/genética , Adulto Joven
8.
J Clin Microbiol ; 48(9): 3306-15, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20592136

RESUMEN

Three hepatitis A virus (HAV) genotypes, I, II, and III, divided into subtypes A and B, infect humans. Genotype I is the most frequently reported, while genotype II is hardly ever isolated, and its genetic diversity is unknown. From 2002 to 2007, a French epidemiological survey of HAV identified 6 IIA isolates, mostly from patients who did not travel abroad. The possible African origin of IIA strains was investigated by screening the 2008 mandatory notification records of HAV infection: 171 HAV strains from travelers to West Africa and Morocco were identified. Genotyping was performed by sequencing of the VP1/2A junction in 68 available sera. Entire P1 and 5' untranslated regions of IIA strains were compared to reference sequences of other genotypes. The screening retrieved 5 imported IIA isolates. An additional autochthonous case and 2 more African cases were identified in 2008 and 2009, respectively. A total of 14 IIA isolates (8 African and 6 autochthonous) were analyzed. IIA sequences presented lower nucleotide and amino acid variability than other genotypes. The highest variability was observed in the N-terminal region of VP1, while for other genotypes the highest variability was observed at the VP1/2A junction. Phylogenetic analysis identified 2 clusters, one gathering all African and two autochthonous cases and a second including only autochthonous isolates. In conclusion, most IIA strains isolated in France are imported by travelers returning from West Africa. However, the unexplained contamination mode of autochthonous cases suggests another, still to be discovered geographical origin or a French reservoir to be explored.


Asunto(s)
Virus de la Hepatitis A Humana/clasificación , Virus de la Hepatitis A Humana/genética , Hepatitis A/epidemiología , Hepatitis A/virología , Regiones no Traducidas 5' , Adulto , Análisis por Conglomerados , Francia/epidemiología , Genotipo , Virus de la Hepatitis A Humana/aislamiento & purificación , Humanos , Persona de Mediana Edad , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , ARN Viral/genética , Análisis de Secuencia de ADN , Homología de Secuencia , Viaje , Proteínas Estructurales Virales/genética
9.
Antivir Ther ; 14(8): 1183-8, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-20032548

RESUMEN

BACKGROUND: The aim of this study was to assess the influence of hepatitis B virus (HBV) genotypes on serum hepatitis B surface antigen (HBsAg) kinetics in hepatitis B e antigen (HBeAg)-negative patients treated with pegylated interferon-alpha2a (PEG-IFN-alpha2a). METHODS: A total of 48 consecutive patients treated with PEG-IFN-alpha2a (180 microg/week) for 48 weeks were assessed. HBV genotype was determined. Serum HBV DNA and HBsAg were assessed at baseline, during treatment (weeks 12, 24 and 48) and during follow-up (weeks 72 and 96). RESULTS: The distribution of HBV genotype was A 27%, B 17%, C 12%, D 29% and E 14%. Mean +/-sd pretreatment serum HBV DNA (6.9 +/-1.5 log(10) copies/ml) was not different between genotypes and decreased under treatment in all genotypes without significant difference. Mean +/-sd pretreatment serum HBsAg (3.6 +/-0.6 log(10) IU/ml) was significantly different between genotypes (P<0.001), with high levels in genotypes A and C, intermediate levels in genotypes D and E, and low levels in genotype B (4.0 +/-0.3, 4.1 +/-0.7, 3.6 +/-0.5, 3.6 +/-0.4 and 2.7 +/-0.6 log(10) IU/ml, respectively). Serum HBsAg decreased under treatment in all genotypes with a significant difference. At the end of treatment, mean +/-sd decrease was high in genotype A, intermediate in genotypes B and D, and low in genotypes C and E (1.3 +/-1.6, 0.7 +/-0.7, 0.6 +/-0.9, 0.4 +/-1.0 and 0.4 +/-0.9 log(10) IU/ml, respectively; P<0.001). During follow-up, serum HBsAg continued to decrease in genotypes A and D, whereas rebound was observed in genotypes B, C and E. CONCLUSIONS: HBV genotype has a strong influence on serum HBsAg kinetics during PEG-IFN-alpha2a therapy in HBeAg-negative patients.


Asunto(s)
Antivirales/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Antivirales/administración & dosificación , ADN Viral/sangre , Femenino , Genotipo , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Cinética , Masculino , Polietilenglicoles/administración & dosificación , Proteínas Recombinantes , Resultado del Tratamiento
10.
J Hepatol ; 50(6): 1084-92, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19376603

RESUMEN

BACKGROUND/AIMS: To assess the HBsAg seroconversion rate and its impact on the long-term outcome in chronic hepatitis B patients treated with conventional interferon, and to analyze the serum HBsAg concentration prior to seroconversion. METHODS: Ninety-seven HBeAg-positive patients were retrospectively evaluated. Sustained virological response (SVR) was defined as HBeAg seroconversion and undetectable serum HBV-DNA 48 weeks after treatment discontinuation. HBsAg level was assessed at yearly intervals until seroconversion in SVRs. RESULTS: Twenty-five patients (26%) achieved SVR. By multivariate analysis, SVR was associated with low serum HBV DNA level and severe liver fibrosis. During a median follow-up of 14 years (range, 5-20 years), 28 patients (29%) developed HBsAg seroconversion including 16 SVRs (64%) and 12 non-SVRs (16%), p < 0.001. HBsAg quantification showed a major decrease (median = 46%, range = 19-100%) in the first year after interferon starting in SVR patients. Six patients developed hepatocellular carcinoma, none of them had undergone HBsAg seroconversion. Liver fibrosis improved in 70% of patients with HBsAg seroconversion compared to 30% of those without HBsAg seroconversion (p < 0.01). CONCLUSIONS: HBsAg seroconversion is achieved with a high steady rate in patients responding to interferon, and associated with excellent outcome. Prospective studies are needed to clarify the utility of on-treatment quantitative serum HBsAg in interferon-based therapy.


Asunto(s)
Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/inmunología , Interferones/uso terapéutico , Adulto , Anciano , Antivirales/uso terapéutico , Carcinoma Hepatocelular/etiología , ADN Viral/sangre , Femenino , Estudios de Seguimiento , Anticuerpos contra la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Virus de la Hepatitis B/patogenicidad , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/virología , Humanos , Hígado/patología , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
11.
Hepatology ; 49(4): 1151-7, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19115222

RESUMEN

UNLABELLED: Pegylated interferon alfa-2a (PEG-IFN) may induce sustained virological response (SVR) in 20% of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients. In addition, loss of hepatitis B surface antigen (HBsAg) is achieved with a 10% yearly rate after treatment cessation in sustained responders. The aim of this study was to assess on-treatment serum HBsAg kinetics to predict SVR in HBeAg-negative patients treated with PEG-IFN. Forty-eight consecutive patients were treated with PEG-IFN (180 microg/week) for 48 weeks. Serum hepatitis B virus (HBV) DNA (COBAS TaqMan) and HBsAg (Abbott Architect HBsAg QT assay) were assessed at baseline, during treatment (weeks 12, 24, and 48), and during follow-up (weeks 72 and 96). SVR was defined as undetectable serum HBV DNA (<70 copies/mL) 24 weeks after treatment cessation. Twenty-five percent of patients achieved SVR. They were not different from those who failed treatment regarding age, sex, ethnicity, HBV genotype, baseline serum HBV DNA and HBsAg levels, or liver histology. During treatment, serum HBsAg levels decreased only in patients who developed SVR, with mean decreases of 0.8 +/- 0.5, 1.5 +/- 0.6, and 2.1 +/- 1.2 log(10) IU/mL at weeks 12, 24, and 48, respectively. A decrease of 0.5 and 1 log(10) IU/mL in serum HBsAg levels at weeks 12 and 24 of therapy, respectively, had high predictive values of SVR (negative predictive value [NPV] 90%, positive predictive value [PPV] 89% for week 12; NPV 97%, PPV 92% for week 24). HBsAg loss was observed in three patients, all with SVR. CONCLUSION: Early serum HBsAg drop has high predictive values of SVR to PEG-IFN in HBeAg-negative CHB patients. Serum quantitative HBsAg may be a useful tool to optimize the management of PEG-IFN therapy in these patients.


Asunto(s)
Antivirales/uso terapéutico , ADN Viral/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Adulto , Femenino , Antígenos e de la Hepatitis B/sangre , Hepatitis B Crónica/inmunología , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Proteínas Recombinantes
12.
J Acquir Immune Defic Syndr ; 46(1): 12-8, 2007 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-17514016

RESUMEN

BACKGROUND: Surveillance of HIV-1 drug resistance in antiretroviral-treated patients is important from the public health perspective of the spread of resistance and to evaluate the proportion of patients for whom new drugs are needed. METHODS: Patients were consecutively included in 28 centers in France and 1 center in Switzerland if they had a viral load measurement performed in June 2004, with a result >or=1,000 copies/mL. Reverse transcriptase, protease, and gp41 genes were sequenced, and resistance mutations were reported as listed on the Web site ( www.iasusa.org). The genotypic resistance results were interpreted by the Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS) and Stanford algorithms. RESULTS: The 498 patients included had been exposed to 9 (interquartile ratio [IQR]: 6 to 12) antiretroviral drugs. Patients' viruses harbored 4 nucleoside reverse transcriptase inhibitor (IQR: 1 to 6) and 4 protease inhibitor (PI; IQR: 2 to 8) resistance mutations, whereas 44% had at least 1 nonnucleoside reverse transcriptase inhibitor resistance mutation. The frequency of resistance to at least 1 drug was 88% with the ANRS algorithm and 83% with the Stanford algorithm. The frequencies of complete resistance to 1, 2, and 3 classes of drugs were 37%, 15%, and 4%, respectively, with the ANRS algorithm and 27%, 23%, and 24%, respectively, with the Stanford algorithm. The most important differences between algorithms were for PIs. Using the ANRS algorithm and extrapolation on the whole French database, 19% of all treated patients could contribute to the spread of resistance and 4% had complete resistance to 2 classes of antiretroviral drugs. CONCLUSIONS: The observed patterns of resistance are linked to a long-lasting history of antiretroviral therapy. The frequency of multiresistance can vary according to the interpretation systems.


Asunto(s)
Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral Múltiple , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Adulto , Femenino , Francia/epidemiología , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia
14.
Gastroenterol Clin Biol ; 29(5): 573-6, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15980754

RESUMEN

AIM: Diagnosis of acute hepatitis A virus (HAV) infection is classically based on the detection of HAV-IgM. Nevertheless, HAV-IgM can be positive for patients with polyclonal stimulation of their immune system (i.e. immune reactivation). To improve the diagnostic yield, an avidity test for HAV-IgG antibodies was developed and tested. METHODS: Avidity tests were performed in 128 sera: 11 selected samples from patients with past infection, 15 acute hepatitis A, 10 vaccinated subjects and 4 patients with immune reactivation as well as 84 HAV-IgM positive unselected sera, provided by routine laboratories. RESULTS: Patients with past infection had avidities over 70%, whereas avidities in patients with acute hepatitis A were below 50% during the first month following the onset of symptoms. As expected, patients with immune reactivation had avidities over 70% consistent with past infection. The results obtained for the 84 unselected sera allowed reconsidering the diagnosis of acute hepatitis A for nearly a third of patients. CONCLUSION: This test could improve the diagnosis of acute hepatitis A infection, particularly in elderly patients.


Asunto(s)
Afinidad de Anticuerpos , Hepatitis A/diagnóstico , Hepatitis A/inmunología , Inmunoglobulina G/inmunología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , Diagnóstico Diferencial , Femenino , Humanos , Inmunoglobulina G/análisis , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Pruebas Serológicas
15.
Antimicrob Agents Chemother ; 49(5): 1720-6, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15855487

RESUMEN

The genotypic inhibitory quotient (GIQ) has been proposed as a way to integrate drug exposure and genotypic resistance to protease inhibitors and can be useful to enhance the predictivity of virologic response for boosted protease inhibitors. The aim of this study was to evaluate the predictivity of the GIQ in 116 protease inhibitor-experienced patients treated with lopinavir-ritonavir. The overall decrease in human immunodeficiency virus type 1 (HIV-1) RNA from baseline to month 6 was a median of -1.50 log(10) copies/ml and 40% of patients had plasma HIV-1 RNA below 400 copies/ml at month 6. The overall median lopinavir study-state C(min) concentration was 5,856 ng/ml. Using univariate linear regression analyses, both lopinavir GIQ and the number of baseline lopinavir mutations were highly associated with virologic response through 6 months. In the multivariate analysis, only lopinavir GIQ, baseline HIV RNA, and the number of prior protease inhibitors were significantly associated with response. When the analysis was limited to patients with more highly mutant viruses (three or more lopinavir mutations), only lopinavir GIQ remained significantly associated with virologic response. This study suggests that GIQ could be a better predictor of the virologic response than virological (genotype) or pharmacological (minimal plasma concentration) approaches used separately, especially among patients with at least three protease inhibitor resistance mutations. Therapeutic drug monitoring for patients treated by lopinavir-ritonavir would likely be most useful in patients with substantially resistant viruses.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/efectos de los fármacos , Pirimidinonas/uso terapéutico , Ritonavir/uso terapéutico , Adulto , Anciano , Combinación de Medicamentos , Monitoreo de Drogas , Femenino , Genotipo , VIH-1/genética , Humanos , Modelos Lineales , Lopinavir , Masculino , Persona de Mediana Edad , Mutación/genética , Valor Predictivo de las Pruebas , ARN Viral/genética
16.
J Med Virol ; 76(2): 271-8, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15834883

RESUMEN

Investigation of hepatitis A virus (HAV) outbreaks often implies nucleotide sequence analysis. As an alternative method for the identification of related strains, single strand conformation polymorphism method (SSCP) was compared to sequence analysis. Twenty-three strains from sporadic and outbreak cases were studied retrospectively. SSCP, sequence identity and phylogenetic analyses were conducted on a 267 bp fragment of the VP1-2A variable region. The results of SSCP pattern comparison and sequence identity were highly correlated (r = 0.92, P < 0.001). If SSCP showed similar patterns, the VP1-2A fragments had a high and significant probability to have a sequence identity over 99.6%. Results were concordant for outbreak strains. The only discordant result concerned a cluster of three sporadic cases evidenced by phylogenetic analysis while SSCP showed similar patterns for only two of these three cases. A prospective SSCP analysis of a recent HAV outbreak confirmed the reliability of this technique. SSCP may thus provide a rapid and cost-effective tool for preliminary investigation of HAV outbreaks, before undertaking exhaustive nucleotide sequence analysis.


Asunto(s)
Brotes de Enfermedades , Virus de la Hepatitis A/clasificación , Virus de la Hepatitis A/genética , Hepatitis A/epidemiología , Hepatitis A/virología , Polimorfismo Conformacional Retorcido-Simple , Adolescente , Adulto , Niño , Preescolar , Cisteína Endopeptidasas/genética , Femenino , Virus de la Hepatitis A/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Filogenia , Estudios Retrospectivos , Análisis de Secuencia de ADN , Proteínas Virales/genética , Proteínas Estructurales Virales/genética
17.
J Clin Microbiol ; 42(11): 5121-4, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15528704

RESUMEN

Diagnosis of acute hepatitis A virus (HAV) infection is based on the detection of HAV immunoglobulin M (IgM). However, IgM could be detected due to nonspecific polyclonal activation of the immune system. An avidity test for anti-HAV IgG was developed to distinguish acute infection, where low-avidity antibodies are detected, from immune reactivation. The assay was tested on 104 samples, including 11 sera from patients with past infection, 15 sera from patients with acute infection and 4 collected after recovery, 10 sera from vaccinated subjects, 4 sera from patients with suspected immune reactivation, and 60 unselected HAV-IgM positive sera, collected over 1 year in a routine laboratory. The avidity index (AI) was expressed as percentage. The results were provided as the mean +/- one standard deviation. Patients with a history of prior infection had AIs of >70% (mean, 86% +/- 10), whereas the mean AI was 36% +/- 16 during acute HAV infection (P < 0.001). Within the first month after the onset of hepatitis, avidity was either noncalculable due to a very low IgG titer or <50%. In patients with immune reactivation, avidity was >70% (88% +/- 10%), a finding consistent with a prior infection. Among the 60 unselected sera, 35 (58%) had a noncalculable or <50% avidity, and most of them had a detectable HAV RNA, confirming HAV infection. In contrast, 16 (27%) had an avidity of >70%, and none was reverse transcription-PCR positive, suggesting immune reactivation. These 16 patients were significantly older than the others (50 +/- 16 years versus 26 +/- 14 years). The new anti-HAV IgG avidity assay we developed could improve HAV infection diagnosis, particularly in elderly patients.


Asunto(s)
Afinidad de Anticuerpos , Anticuerpos de Hepatitis A/inmunología , Virus de la Hepatitis A/inmunología , Hepatitis A/diagnóstico , Inmunoglobulina G/inmunología , Hepatitis A/virología , Anticuerpos de Hepatitis A/sangre , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre
18.
J Clin Microbiol ; 42(9): 4329-31, 2004 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-15365037

RESUMEN

Hepatitis A virus (HAV) is shed in feces but also in saliva. HAV RNA was detected in saliva in five out of six acutely infected patients with HAV viremia. Serum and saliva sequences were identical. The simplicity of obtaining material allows the recommendation of the use of saliva for investigation of outbreaks.


Asunto(s)
Virus de la Hepatitis A/aislamiento & purificación , Hepatitis A/diagnóstico , ARN Viral/análisis , Saliva/virología , Adolescente , Adulto , Brotes de Enfermedades , Femenino , Hepatitis A/sangre , Virus de la Hepatitis A/clasificación , Humanos , Masculino , Persona de Mediana Edad , Filogenia , ARN Viral/sangre , Reproducibilidad de los Resultados
20.
Antivir Ther ; 8(6): 627-34, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14760897

RESUMEN

Sera from 12 patients infected with human immunodeficiency virus and hepatitis B virus (HBV), on lamivudine as part of an antiretroviral therapy, were retrospectively analysed for the presence of HBV polymerase mutations by the line probe assay, INNO-LiPA HBV DR, and by the direct sequencing assay, TRUGENE HBV genotyping kit. Results at codons 180, 204 and 207 were compared for 44 samples. Full concordance was observed for 81.4% of the 129 analysed codons. Discordance involved only mixed populations: LiPA detected additional species in 19 codons and TRUGENE in five. Viral breakthrough occurred in seven patients, 12-33 months after lamivudine initiation. In five cases with close sampling available, both assays detected mutations before the rise in viral load, although earlier by LiPA for three patients. The time interval between the first mutant detection and viral escape ranged from 2 to 22 months. Mutations were detected in four of the five remaining patients: 1) at therapy initiation in a primary non-responder; 2) after 37 months, but replication became undetectable after tenofovir introduction; 3) transiently at 6 months by LiPA but treatment was ceased thereafter; 4) after 23 months but replication levels remained low during a 5-year follow-up. Interestingly, TRUGENE sequencing identified on late samples from three patients a variant carrying rtV173L plus rtL180M plus M204V mutations, having the in vitro characteristics of 'vaccine escape' mutants. Both assays appear to be valuable tools for the early detection of mutated HBV strains. The detection of genotypic therapeutic decision-making, although clinical or other virological factors may determine the rapidity of the viral breakthrough.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/virología , Productos del Gen pol/genética , VIH-1 , Virus de la Hepatitis B/genética , Hepatitis B/virología , Lamivudine/uso terapéutico , Mutación , Adulto , Anciano , ADN Viral/análisis , Farmacorresistencia Viral , Genotipo , Hepatitis B/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Juego de Reactivos para Diagnóstico , Análisis de Secuencia de ADN
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