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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.
Int J Antimicrob Agents ; 53(1): 80-83, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30236959

RESUMEN

More data on resistance of HCV genotype (GT) 3 and 4 to direct-acting antivirals (DAAs) are still needed. Here we investigated the presence of resistance-associated substitutions (RASs) pre- and post-treatment and their emergence under DAAs in HCV GT3- and GT4-infected patients failing DAA regimens by next-generation sequencing (NGS). Sanger sequencing and NGS were performed on NS5B and NS5A in plasma samples prior to and post treatment of 13 patients. Positions implicated in resistance to anti-NS5A and anti-NS5B in the literature were analysed. No baseline RASs was detected in NS5B but one GT4r virus developed the mutation S282T at failure. In NS5A, pre-existing RASs or polymorphisms were detected in viruses of 6/10 patients (L28M for a GT4a, M28V for a GT4r, L30R for a GT4a, 2 GT4d and 1 GT4r, and T58P for a GT4d) by Sanger sequencing and in viruses of 7/10 patients by NGS. Additional baseline minority substitutions detected by NGS were Y93H in a GT3a, L28M in a GT4a and GT4d, and L28F in a GT4d virus. At failure, these substitutions were found at a frequency of 100%. Y93H was detected alone at baseline, whilst L28M and L28F were accompanied by polymorphisms L30R or L30R + T58P. Use of NGS in patients failing DAAs and infected by HCV GT3 and GT4 revealed the emergence of specific patterns of substitutions in NS5A and NS5B, in particular substitutions at position 28 in NS5A in GT4 virus, highlighting the need to list these substitutions in guidelines for resistance interpretation.


Asunto(s)
Antivirales/uso terapéutico , Genotipo , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Proteínas no Estructurales Virales/genética , Sustitución de Aminoácidos , Farmacorresistencia Viral , Femenino , Hepatitis C/virología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Persona de Mediana Edad , Técnicas de Amplificación de Ácido Nucleico , Insuficiencia del Tratamiento
4.
J Virol Methods ; 257: 12-15, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29588254

RESUMEN

In-depth study of HIV often requires large stock of patients-derived viruses obtained through viral cultures. HIV cultures are currently limited by low recovery rates, especially when viral load is below 100,000 copies per mL. This is problematic for HIV-2 as most patients have spontaneously low to undetectable viremia. New approaches have been developed to enhance viral recovery rates but they are complex or costly to implement. We tested the impact of µMACSTM VitalVirus Isolation Kit (Miltenyi), a HIV virions capture method using paramagnetic microbeads directed against CD44, a human glycoprotein present in HIV envelope. This method separates viruses from interfering proteins in 45 min, using a reduced sample volume (200 µL versus 1000 µL for classic culture assays). The impact of this purification method on virus recovery rate was assessed with 23 HIV-1 and 29 HIV-2 plasma samples with a wide range of viral loads, in comparison to a classic culture assay used routinely in our laboratory. For both HIV-1 and HIV-2, the culture identification delay was decreased using viral purification (≤7days in most cases). The recovery rate of cultures was improved for HIV-2 isolates (17/29 versus 8/29; p = 0.03) but not for HIV-1 (7/23 versus 5/23; p = 0.74). Notably, HIV-2 isolates with viral loads over 10,000 copies per mL were frequently recovered in culture (68% versus 32% without purification; p = 0.03). This marked improvement on HIV-2, but not on HIV-1, cultures is puzzling. CD44-microbeads may enable a close and prolonged contact between cells and viruses, and may thus overcome HIV-2 difficulties to infect target cells.


Asunto(s)
Anticuerpos/metabolismo , Infecciones por VIH/virología , VIH-2/aislamiento & purificación , Receptores de Hialuranos/metabolismo , Separación Inmunomagnética , Cultivo de Virus/métodos , Anticuerpos/inmunología , VIH-1/aislamiento & purificación , Humanos , Receptores de Hialuranos/inmunología
5.
J Clin Virol ; 96: 49-53, 2017 11.
Artículo en Inglés | MEDLINE | ID: mdl-28950186

RESUMEN

BACKGROUND: The new Roche Cobas 6800 platform (C6800) has been recently introduced for viral load (VL) measurement. OBJECTIVES: Comparing C6800 to Cobas Ampliprep/Cobas TaqMan v2.0 (CAP/CTM) for the quantification of HIV, HBV and HCV viremia, and to the Abbott RealTime assay (ABB) for HCV quantification. STUDY DESIGN: We analysed 121 samples for HBV, and 139 for HIV-1 including 2 groupO and 137 group M viruses (36.5% subtype B, 27.0% CRF02_AG, 22.6% from other clades, and 14% subtype not available). For the 100 HCV samples compared with CAP/CTM, 42% were genotype 1 and 17% were genotype 4. For the 68 HCV samples compared with ABB, 52.9% were genotype 1 and 22.1% were genotype 4. RESULTS: C6800 results correlated well with those of CAP/CTM for all three viruses (R2: 0.97-0.99). However, C6800 can yield different viraemia results: higher for HIV (mean difference: +0.11 log10copies/mL, p<0.0001), and lower for HBV (mean difference:-0.11 log10 IU/mL, p<0.0001). Differences exceeded 0.5 log10 for 6.5% of HIV-1 samples and 7.4% of HBV samples. For HCV quantification, C6800 gave mostly lower values than the other assays towards the bottom of the range, and higher values in the upper part of the range, especially in comparisons with ABB, for which 28% of differences exceeded 0.5 log10 IU/mL. No particular HCV genotype was identified as responsible for these differences. CONCLUSION: Overall, the comparison tests between C6800 and CAP/CTM systems are satisfactory for the three viruses. Frequent discrepancies were observed between C6800 and ABB for HCV.


Asunto(s)
VIH/aislamiento & purificación , Hepacivirus/aislamiento & purificación , Virus de la Hepatitis B/aislamiento & purificación , Técnicas de Diagnóstico Molecular/métodos , Carga Viral/métodos , Viremia/diagnóstico , Humanos
7.
J Hepatol ; 65(1): 40-47, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26952005

RESUMEN

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is an independent risk factor for chronic kidney disease and leads to faster liver disease progression in patients requiring hemodialysis than in those with normal renal function. Little is known about the use of a sofosbuvir-containing regimen for infected patients on hemodialysis. We aimed to describe the pharmacokinetics, safety and efficacy of sofosbuvir in 2 dosing regimens and associated antiviral agents in HCV-infected patients requiring hemodialysis. METHODS: Multicenter, prospective and observational study of patients receiving sofosbuvir, 400mg once daily (n=7) or 3 times a week (n=5), after hemodialysis with simeprevir, daclatasvir, ledipasvir or ribavirin was conducted. Drug plasma concentrations were determined by liquid chromatography-tandem mass spectrometry before and after a 4h hemodialysis and 1.5h after last drug intake at the end of hemodialysis. RESULTS: Plasma concentrations of sofosbuvir or its inactive metabolite sofosbuvir-007 did not accumulate with either regimen between hemodialysis sessions or throughout the treatment course. Sofosbuvir-007 extraction ratio (52%) was consistent with historical data. In one patient receiving the once daily regimen, sofosbuvir-007 half-life was slightly higher (38h) than for patients with normal renal function receiving a full dose. Hemodialysis did not remove any other associated anti-HCV agents. Clinical and biological tolerance was good for all patients. Two relapses occurred with the 3 times a week regimen and none with the once daily. CONCLUSIONS: A regimen including sofosbuvir, 400mg once daily, could be proposed for HCV-infected patients requiring hemodialysis and should be associated with close clinical, biological, cardiovascular, and therapeutic drug monitoring. LAY SUMMARY: Hepatitis C Virus (HCV) infection in hemodialysis patients is prevalent and aggressive. Effective anti-HCV treatment in these patients may stabilize their renal disease. However, sofosbuvir, the cornerstone of most anti-HCV-containing regimens, should not be administered to these patients until more data is available. In this pharmacokinetic study, sofosbuvir full dose (400mg once daily) administered every day with another direct antiviral agent did not accumulate in hemodialysis patients and was safe and effective.


Asunto(s)
Hepatitis C Crónica , Antivirales , Quimioterapia Combinada , Genotipo , Hepacivirus , Humanos , Estudios Prospectivos , Diálisis Renal , Ribavirina , Simeprevir , Sofosbuvir
8.
AIDS ; 29(7): 779-84, 2015 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-25985400

RESUMEN

OBJECTIVE: In HIV-1, hypermutation introduced by APOBEC3F/3G cytidine deaminase activity leads to defective viruses. In-vivo impact of APOBEC3F/3G editing on HIV-2 sequences remains unknown. The objective of this study was to assess the level of APOBEC3F/3G editing in HIV-2-infected antiretroviral-naive patients. METHODS: Direct sequencing of vif and pol regions was performed on HIV-2 proviral DNA from antiretroviral-naive patients included in the French Agence Nationale de Recherches sur le SIDA et les hépatites virales CO5 HIV-2 cohort. Hypermutated sequences were identified using Hypermut2.0 program. HIV-1 proviral sequences from Genbank were also assessed. RESULTS: Among 82 antiretroviral-naive HIV-2-infected patients assessed, 15 (28.8%) and five (16.7%) displayed Vif proviral defective sequences in HIV-2 groups A and B, respectively. A lower proportion of defective sequences was observed in protease-reverse transcriptase region. A higher median number of G-to-A mutations was observed in HIV-2 group B than in group A, both in Vif and protease-reverse transcriptase regions (P = 0.02 and P = 0.006, respectively). Compared with HIV-1 Vif sequences, a higher number of Vif defective sequences was observed in HIV-2 group A (P = 0.00001) and group B sequences (P = 0.013). CONCLUSION: We showed for the first time a high level of APOBEC3F/3G editing in HIV-2 sequences from antiretroviral-naive patients. Our study reported a group effect with a significantly higher level of APOBEC3F/3G editing in HIV-2 group B than in group A sequences.


Asunto(s)
Citidina Desaminasa/metabolismo , Citosina Desaminasa/metabolismo , VIH-2/genética , ARN Viral/metabolismo , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen vif del Virus de la Inmunodeficiencia Humana/genética , Desaminasa APOBEC-3G , Adulto , Estudios de Cohortes , Biología Computacional , ADN Viral/química , ADN Viral/genética , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Provirus/genética , Análisis de Secuencia de ADN
9.
Liver Int ; 35(2): 409-16, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24698736

RESUMEN

BACKGROUND & AIMS: Mother-to-child (MTC) hepatitis B virus (HBV) transmission has been mainly studied in Asia. The geographical origins of women and HBV genotypes differ in Europe. The aims were to determine the rate and risk factors of MTC HBV transmission from women with high HBV DNA loads in a maternity hospital in Paris, France. METHODS: Retrospective study of HIV-negative, HBs Ag-positive pregnant women with HBV DNA loads above 5 Log10 I.U/ml who were not given lamivudine or tenofovirDF during pregnancy between 2004 and 2011. RESULTS: Among 11 417 pregnant women, 437 (4%) showed a positive HBs Ag. Among these women, 52 had HBV DNA loads above 5 Log10 I.U/ml: 41, 10 and 1 born in Asia, sub-Saharan Africa and Europe respectively. Among the 52 women, 40 were eligible for the analysis: no antiviral therapy during pregnancy; children over 9 months old. Twenty-eight (70%) women were assessed, corresponding to 41 childbirths. Eleven children (27%) had positive HBs Ag, 14 (34%) had positive HBc and HBs Ab, 16 (39%) had positive HBs Ab only. The risk of having positive HBs Ag, according to maternal HBV DNA loads, was 14% for HBV DNA loads less or equal to 8 Log10 I.U/ml, 42% for HBV DNA loads over 8 Log10 I.U/ml, P = 0.04, but not related to the women's origin, HBV genotype. CONCLUSIONS: This study confirms that serovaccination does not fully protect newborns from MTC HBV transmission, when maternal HBV DNA loads exceed 5 Log10 I.U/ml, regardless of the women's origin or HBV genotype.


Asunto(s)
Hepatitis B/epidemiología , Hepatitis B/transmisión , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , África del Sur del Sahara/etnología , Análisis de Varianza , Anticuerpos Antivirales/sangre , Asia/etnología , Secuencia de Bases , Análisis por Conglomerados , ADN Viral/sangre , Femenino , Hepatitis B/genética , Vacunas contra Hepatitis B/administración & dosificación , Humanos , Recién Nacido , Masculino , Datos de Secuencia Molecular , Paris/epidemiología , Filogenia , Embarazo , Estudios Retrospectivos , Medición de Riesgo , Análisis de Secuencia de ADN , Vacunación/estadística & datos numéricos , Carga Viral
10.
AIDS ; 27(18): 2959-61, 2013 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-23942060

RESUMEN

In this study, we assessed phenotypic susceptibility to dolutegravir and raltegravir in a large variety of HIV-1 'non-B' subtypes (n = 72) issued from integrase inhibitor-naive clinical isolates. All samples were susceptible to both dolutegravir and raltegravir with median IC50 values of 1.22 nmol/l and 1.53 nmol/l, respectively; similar to that observed for the B subtype. Thus, despite the high prevalence of polymorphic substitutions in integrase in 'non-B' clinical isolates, phenotypic susceptibility to dolutegravir remained unchanged.


Asunto(s)
Fármacos Anti-VIH/farmacología , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Compuestos Heterocíclicos con 3 Anillos/farmacología , Pirrolidinonas/farmacología , Genotipo , Integrasa de VIH/genética , VIH-1/aislamiento & purificación , Humanos , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Mutación Missense , Oxazinas , Piperazinas , Piridonas , Raltegravir Potásico
11.
J Clin Virol ; 58(2): 385-90, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23953940

RESUMEN

BACKGROUND: Saliva sampling may provide an easier access to hepatitis C virus (HCV) screening test. HIV infection influence on specific salivary antibody detection has not been extensively studied. OBJECTIVES: An anti-HCV antibodies (HCV-Ab) test was adapted for saliva specimens and its performances were analysed according to the patients' HIV status and related factors such as CD4 cell counts and HIV viral load. METHODS: Four patients groups were selected: (i) HCV and HIV negative volunteers (n=28); (ii) HCV positive and HIV negative patients (n=30); (iii) HCV negative and HIV positive patients (n=30); (iv) HCV and HIV co-infected patients (n=30). Saliva samples were collected (Salivette system, Sarstedt) and an in-house adapted HCV-Ab detection assay was performed (MONOLISA anti-HCV PLUS Version 2, Biorad). HIV viral load, CD4 cells counts and HCV viremic status were reported. RESULTS: Sensitivity and specificity of saliva anti-HCV antibody tests in the HIV negative groups were 90% and 100%, respectively, compared to 73% and 93%, respectively in the HIV infected population. Compared to the HIV negative population, HIV mono-infected patients presented higher absorbance values (p=0.01) and HIV/HCV co-infected population presented lower HCV-Ab absorbance values (p<0.001). Sensitivity decline was associated with HIV replication (p=0.02), HCV replication (p=0.16) but not with CD4 cell counts (p=0.64). CONCLUSION: Performances of salivary HCV antibodies testing are strongly deteriorated in the HIV positive population, especially for patients with residual HIV replication. This serious limitation should prompt careful testing of non-invasive screening tests for hepatitis C in HIV-infected patients before use in real screening conditions.


Asunto(s)
Infecciones por VIH/complicaciones , Anticuerpos contra la Hepatitis C/análisis , Hepatitis C/diagnóstico , Pruebas Inmunológicas/métodos , Saliva/inmunología , Adulto , Recuento de Linfocito CD4 , Femenino , VIH/aislamiento & purificación , Hepatitis C/inmunología , Humanos , Inmunoensayo/métodos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Carga Viral
12.
J Antimicrob Chemother ; 68(10): 2197-8, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23749952

RESUMEN

OBJECTIVES: To assess the prevalence of the K65R, K103N and M184V/I resistance mutations in the reverse transcriptase (RT) region in HIV-1-infected patients failing antiretroviral-based regimens between the years 2005 and 2010. PATIENTS AND METHODS: HIV-1-infected patients experiencing virological failure between 2005 and 2010 with RT genotypic resistance tests available at the time of virological failure were analysed. K65R, K103N and M184V/I mutation frequencies were determined each year. Statistical analyses were performed using Fisher's exact test. RESULTS: Among 9586 patients failing their antiretroviral-based regimens from 2005 to 2010, the prevalence of K65R tended to decrease (P = 0.054), while K103N and M184V/I mutation frequencies decreased significantly over time (P < 0.001). The increased use of a tenofovir/emtricitabine/efavirenz single-tablet regimen was associated with decreased selection of these mutations. CONCLUSIONS: The global prevalence of resistance-associated mutations to tenofovir, lamivudine/emtricitabine and efavirenz decreased over time between 2005 and 2010. Despite a stable rate of efavirenz and protease inhibitor use, this phenomenon can be explained by an increased use of single-tablet regimens, which simplify drug intake and maximize adherence.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Transcriptasa Inversa del VIH/genética , VIH-1/genética , Mutación Missense , Sustitución de Aminoácidos , Salud Global , Infecciones por VIH/epidemiología , VIH-1/aislamiento & purificación , Humanos , Estudios Longitudinales , Prevalencia , Estudios Retrospectivos , Insuficiencia del Tratamiento
13.
PLoS One ; 8(3): e59205, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23527135

RESUMEN

OBJECTIVE: The aim of our study was to assess a possible association between plasma inflammatory biomarkers (CRP, IL-6, soluble CD14) and the extent of fibrosis or cirrhosis using a FibroScan® in HIV/HCV co-infected patients. METHODS: This cross-sectional study assessed 60 HIV/HCV co-infected patients who had paired plasma samples and FibroScan® values available. All included patients were controlled for HIV infection (HIV-1 RNA <50 copies/mL) and had detectable HCV RNA levels. Levels of three biomarkers were measured in all samples using commercial ELISA kits. Multivariate logistic regression models identified factors associated with the METAVIR stages of fibrosis (F0-F2 vs. F3-F4). RESULTS: In univariate logistic regression analyses, in addition to sCD14 (odds ratio [OR] = 3.23, 95% confidence interval [95%CI] = 1.30-7.97, P = 0.01), aspartate aminotransferase (AST), alanine aminotransferase, platelet counts, and CD4 cell counts were associated with the stage of liver fibrosis and, thus, were introduced into the model. However, only AST (OR = 1.06, 95%CI = 1.02-1.10, P = 0.0009) was independently associated with F3-F4 stage liver fibrosis. CONCLUSIONS: In our study of HIV/HCV co-infected patients, sCD14 plasma level, a biomarker of monocyte activation, was not independently associated with the F3-F4 stage of liver fibrosis. We hypothesize that the higher levels of inflammation markers observed in HIV/HCV co-infected patients, compared to HCV mono-infected patients, prevent this association being observed within this population.


Asunto(s)
Biomarcadores/sangre , Coinfección/complicaciones , Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/etiología , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Proteína C-Reactiva , Linfocitos T CD4-Positivos/inmunología , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Humanos , Interleucina-6 , Receptores de Lipopolisacáridos , Cirrosis Hepática/sangre , Cirrosis Hepática/enzimología , Modelos Logísticos
15.
J Antimicrob Chemother ; 68(3): 690-6, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23152480

RESUMEN

OBJECTIVES: The aims of the study were to assess in patients with advanced HIV disease receiving antiretroviral therapy (ART) intensification with enfuvirtide (i) resistance at virological failure (VF), (ii) impact of baseline tropism on immunovirological response, and (iii) HIV-1 DNA tropism evolution during ART. METHODS: The ANRS 130 APOLLO randomized trial evaluated in naive patients the immunovirological impact of standard ART without (control arm) or with enfuvirtide. Tropism was determined on RNA and DNA by V3-loop sequencing interpreted using the Geno2Pheno algorithm. RESULTS: At baseline the median CD4 cell count was 30 cells/mm(3). Among the 170 patients assessable in this virological substudy, HIV-1 RNA tropism was as follows: 60% of viruses were R5 and 40% were R5X4/X4. HIV-1 DNA tropism was as follows: 54% were R5 and 46% were R5X4/X4. At week 24, 39% and 49% of patients experienced VF in the enfuvirtide and control arms, respectively. In the enfuvirtide arm, only resistance-associated mutations to enfuvirtide were detected. In the control arm, two patients displayed drug-resistant viruses at the time of VF. No impact of baseline tropism was observed on immunovirological response, regardless of the study arm. Among the 25 patients experiencing DNA tropism switch between baseline and week 24, 16 (64%) switched from R5 to R5X4/X4. These latter were mostly successfully suppressed patients receiving enfuvirtide and exhibiting poorer immunological response. CONCLUSIONS: Baseline RNA tropism had no impact on the immunovirological response. Drug resistance mutations were only detected for the fusion inhibitor. Finally, the mechanism of replenishment of the viral cellular reservoir with X4 viruses observed needs to be further analysed.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Evolución Molecular , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/genética , VIH-1/patogenicidad , Tropismo Viral , Adolescente , Adulto , Anciano , Terapia Antirretroviral Altamente Activa/métodos , Farmacorresistencia Viral , Enfuvirtida , Proteína gp41 de Envoltorio del VIH/administración & dosificación , Humanos , Persona de Mediana Edad , Mutación Missense , Fragmentos de Péptidos/administración & dosificación , Adulto Joven
16.
AIDS ; 27(2): 292-5, 2013 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-23095312

RESUMEN

In this study, assessing HIV-2 tropism among 43 paired plasma/peripheral blood mononuclear cell specimens, the concordance between proviral DNA and plasma RNA genotypic tropism prediction was 74%. All the discordances were attributable to the prediction of R5 in RNA and X4/dual-mixed in DNA. HIV-2 genotypic tropism test based on proviral DNA is a suitable tool for tropism determination in HIV-2-infected patients with low or undetectable viral load.


Asunto(s)
Infecciones por VIH/genética , VIH-2/genética , Tropismo Viral/genética , ADN Viral/sangre , ADN Viral/genética , Genotipo , Infecciones por VIH/sangre , Humanos , Valor Predictivo de las Pruebas , ARN Viral/sangre , ARN Viral/genética , Carga Viral/genética
17.
AIDS ; 27(1): 69-80, 2013 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-23018441

RESUMEN

OBJECTIVE: This study investigated the impact on virological outcome of the gag cleavage sites and the protease-coding region mutations in protease inhibitor-naive and protease inhibitor-experienced patients infected with HIV-2 receiving lopinavir (LPV) containing regimen. METHODS: Baseline gag and protease-coding region were sequenced in 46 HIV-2 group A-infected patients receiving lopinavir. Virological response was defined as plasma viral load less than 100 copies/ml at month 3. Associations between virological response and frequencies of mutations in gag [matrix/capsid (CA), CA/p2, p2/nucleocapsid (NC), NC/p1, p1/p6] and gag-pol (NC/p6) cleavage site and protease-coding region, with respect to the HIV-2ROD strain, were tested using Fisher's exact test. RESULTS: Virological response occurred in 14 of 17 (82%) protease inhibitor-naive and 17 of 29 (59%) protease inhibitor-experienced patients. Virological failure was associated with higher baseline viral load (median: 6765 versus 1098 copies/ml, P = 0.02). More protease-coding region mutations were observed in protease inhibitor-experienced compared with protease inhibitor-naive patients (median: 8 versus 5, P = 0.003). In protease inhibitor-naive patients, T435A (NC/p6), V447M (p1/p6), and Y14H (protease-coding region) were associated with virological failure (P = 0.011, P = 0.033, P = 0.022, respectively). T435A and V447M were associated with Y14H (P = 0.018, P = 0.039, respectively). In protease inhibitor-experienced patients, D427E (NC/p1) was associated with virological response (P = 0.014). A430V (NC/p1) and I82F (protease-coding region) were associated with virological failure (P = 0.046, P = 0.050, respectively). Mutations at position 430 were associated with a higher number of mutations in protease-coding region (median: 10 versus 7, P = 0.008). CONCLUSION: We have demonstrated, for the first time, an association between gag, gag-pol cleavage site and protease-coding region mutations, with distinct profiles between protease inhibitor-naive and protease inhibitor-experienced patients. These mutations might impact the virological outcome of HIV-2-infected patients receiving LPV-containing regimen.


Asunto(s)
Infecciones por VIH/genética , Inhibidores de la Proteasa del VIH/farmacología , VIH-2/genética , Lopinavir/farmacología , Inhibidores de Proteasas/farmacología , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/genética , ADN Viral/efectos de los fármacos , Farmacorresistencia Viral/efectos de los fármacos , Farmacorresistencia Viral/genética , Femenino , Infecciones por VIH/tratamiento farmacológico , Proteasa del VIH/efectos de los fármacos , Proteasa del VIH/genética , VIH-2/efectos de los fármacos , Humanos , Masculino , Datos de Secuencia Molecular , Mutación , Carga Viral/efectos de los fármacos , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/efectos de los fármacos , Productos del Gen pol del Virus de la Inmunodeficiencia Humana/efectos de los fármacos
18.
J Antimicrob Chemother ; 67(6): 1459-61, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22382470

RESUMEN

OBJECTIVES: BMS-626529 is a member of the new drug class of HIV-1 attachment inhibitors currently in development. Mutations selected during in vitro experiments with BMS-626529 are located in the gp120 region: L116P, A204D, M426L, M434I-V506M and M475I. A differential antiviral activity of BMS-626529 was observed depending of the viral subtype. The aim of our study was to assess the prevalence of subtype-related polymorphisms previously described as being associated with in vitro resistance to BMS-626529 in patients infected with different HIV-1 'non-B' subtypes. PATIENTS AND METHODS: The prevalence of substitutions in gp120 was assessed in 85 HIV-infected patients (not previously treated with attachment inhibitors and infected with HIV-1 'non-B' subtypes) by performing direct sequencing of the gp120 region. RESULTS: The most prevalent HIV-1 subtype was CRF02_AG (n = 46, 54%). The M426L substitution was found in virus from 10 patients (11.8%), mainly in subtypes D and CRF02_AG. The M434I substitution was found in virus from 11 patients (12.9%), mainly in subtypes CRF02_AG and CRF06_cpx. None of the CRF02_AG viruses harboured both M426L and M434I substitutions. CONCLUSIONS: In our series, the M426L substitution in the gp120 region was detected in 46% and 7% of subtype D and CRF02_AG samples, respectively, and might affect the activity of BMS-626529 against these specific subtypes. Further studies are needed to better describe associations between HIV-1 'non-B'-subtype-related polymorphism profiles and the level of phenotypic resistance to attachment inhibitor BMS-626529.


Asunto(s)
Fármacos Anti-VIH/farmacología , Farmacorresistencia Viral , Proteína gp120 de Envoltorio del VIH/genética , Inhibidores de Fusión de VIH/farmacología , VIH-1/efectos de los fármacos , VIH-1/genética , Polimorfismo Genético , Sustitución de Aminoácidos , Fármacos Anti-VIH/administración & dosificación , Genotipo , Inhibidores de Fusión de VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/clasificación , VIH-1/aislamiento & purificación , Humanos , Mutación Missense
19.
J Infect Dis ; 205(1): 111-20, 2012 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-22140264

RESUMEN

OBJECTIVE: The use of CCR5 inhibitors requires a tool to predict human immunodeficiency virus type 2 (HIV-2) tropism, as established in HIV-1. The aim of our study was to identify genotypic determinants of HIV-2 tropism located in the gp105 V3 loop. METHODS: HIV-2 tropism phenotypic assays were performed on 53 HIV-2 clinical isolates using GFP expressing human osteosarcoma T4 [GHOST(3)] cell lines expressing CD4 and CCR5 or CXCR4 coreceptors. The gp105 V3 loop was sequenced and analyzed. RESULTS: Thirty-four HIV-2 isolates were classified as R5, 7 as X4, and 12 as X4/R5 (dual). Substitution at residue 18 was always associated with a dual/X4 tropism (P < .00001). The following determinants were associated with dual/X4 tropism: a global net charge of more than +6 (P < .00001), V19K/R mutation (P < .00001), S22A/F/Y mutation (P < .002), Q23R mutation (P < .00001), and insertions at residue 24 (P < .00001), I25L/Y (P < .0004), R28K (P < .0004), and R30K (P < .014). These mutations were not found in R5 isolates, except R28K and R30K, which were detected in 4 and 5 R5 isolates, respectively. The 4 major genotypic determinants of dual/X4 tropism were mutation at residue 18, V19 K/R mutation, insertions at residue 24, and V3 global net charge. CONCLUSIONS: We established a strong association between HIV-2 phenotypic tropism and V3-loop sequences, allowing for the prediction of R5- and/or X4-tropic viruses in HIV-2 infection.


Asunto(s)
Técnicas de Genotipaje/métodos , VIH-2/fisiología , Tropismo Viral/genética , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Secuencia de Bases , Línea Celular Tumoral , Estudios de Asociación Genética , VIH-2/genética , Humanos , Datos de Secuencia Molecular , Mutación , ARN Viral/química , Análisis de Secuencia de ARN
20.
AIDS ; 25(17): 2143-8, 2011 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-21904187

RESUMEN

OBJECTIVE: Recently, we have reported the role of baseline gag cleavage site mutations on the virological outcome of a dual-boosted protease inhibitor regimen in antiretroviral-naive patients (2IP-ANRS 127 trial). The objective of this substudy was to characterize, in patients experiencing virological failure, from the 2IP-ANRS 127 trial, the viral quasispecies present at baseline and at virological failure in gag cleavage site, in gag-pol frameshift and in protease-coding region. METHODS: In four patients, we analysed by clonal analysis the viral population in gag cleavage site (p17/p24, p24/p2, p2/p7, p7/p1, p1/p6(gag)), in p6(gag), in gag-pol frameshift [p1/transframe protein (TFP)/p6(pol)] and in protease-coding region. RESULTS: Clonal analysis of protease-coding region failed to detect major as well as minor protease inhibitor resistance-associated mutations in all four patients. In one patient, a I15V-mutated variant increased from 13 to 100% between baseline and week 24. Clonal analysis of gag and gag-pol cleavage site showed an increase in specific viral populations in p2/p7 cleavage site between baseline and virological failure in three patients. Among them, we described in one patient, that the predominant population at virological failure harboured in p2/p7 and TFP/p6(pol)-specific genotypic profiles associated with duplication of the P(T)APP motif in p6(gag) and the I15V protease mutation on the same individual molecular clones. CONCLUSION: We highlighted the emergence of minority viral populations in the p2/p7 cleavage site between baseline and virological failure. In addition, we showed the association of a specific protease mutation with gag and gag-pol cleavage site substitutions, suggesting their possible role in virological outcome.


Asunto(s)
Infecciones por VIH/genética , Inhibidores de la Proteasa del VIH/administración & dosificación , VIH-1 , Mutación , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Células Clonales , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Humanos , Reacción en Cadena de la Polimerasa , ARN Viral , Reacción en Cadena en Tiempo Real de la Polimerasa , Insuficiencia del Tratamiento , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/efectos de los fármacos , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/metabolismo
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