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1.
Infect Dis Now ; 51(5): 451-455, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34366081

RESUMO

INTRODUCTION: Ultrasound imaging has many clinical applications, but there is a lack of data about its use by infectiologists. The aim of this study was to describe ultrasound performed routinely by infectiologists and to assess the diagnostic performance of ultrasound with aspirate and fluid analysis in prosthetic joint infections. METHODS: Retrospective study between 1st June 2019 and 1st June 2020 in an infectious and tropical diseases unit in a tertiary University Hospital. RESULTS: One hundred and thirty-one ultrasounds were performed on 127 patients by the infectious diseases team. These included 64 musculoskeletal ultrasounds (31 in native joints and 33 in prosthetic joints including 15 knees, 13 hips and 5 spacers) and 33 led to a fluid aspirate. Fourteen lung ultrasounds were done, 11 confirmed pneumopathy and 7 resulted in pleural puncture. Twenty-three vascular ultrasounds were done, 17 to insert a catheter, and four to perform a blood test. Five ultrasounds explored adenopathy, of which one node tuberculosis and one Bartonella infection were diagnosed. In prosthetic joint infections, sensitivity and specificity of ultrasound with fluid aspirate and analysis were respectively 100% and 100% for the knee and 40% and 100% for the hip. CONCLUSION: Ultrasound performed by infectiologists is useful and contributes to a faster diagnosis. Furthermore, the specificity of ultrasound with aspirate and fluid analysis is very high in prosthetic joint infection. Ultrasound training courses should be considered for infectiologists including residents.


Assuntos
Artrite Infecciosa , Infecções Relacionadas à Prótese , Humanos , Infecções Relacionadas à Prótese/diagnóstico por imagem , Estudos Retrospectivos , Líquido Sinovial , Ultrassonografia
2.
BMC Infect Dis ; 20(1): 850, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198667

RESUMO

BACKGROUND: The objective of the study was to describe the evolution of chronic non-AIDS related diseases and their risk factors, in patients living with HIV (PLHIV) in the French ANRS CO3 Aquitaine prospective cohort, observed both in 2004 and in 2014 in order to improve long-term healthcare management. METHODS: The ANRS CO3 Aquitaine cohort prospectively collects epidemiological, clinical, biological and therapeutic data on PLHIV in the French Aquitaine region. Two cross sectional analyses were performed in 2004 and 2014, to investigate the patient characteristics, HIV RNA, CD4 counts and prevalence of some common comorbidities and treatment. RESULTS: 2138 PLHIV (71% male, median age 52.2 years in 2014) were identified for inclusion in the study, including participants who were registered in the cohort with at least one hospital visit recorded in both 2004 and 2014. Significant increases in the prevalence of diagnosed chronic kidney disease (CKD), bone fractures, cardiovascular events (CVE), hypertension, diabetes and dyslipidaemia, as well as an increase in treatment or prevention for these conditions (statins, clopidogrel, aspirin) were observed. It was also reflected in the increase in the proportion of patients in the "high" or "very high" risk groups of the disease risk scores for CKD, CVE and bone fracture score. CONCLUSIONS: Between 2004 and 2014, the aging PLHIV population identified in the French ANRS CO3 Aquitaine prospective cohort experienced an overall higher prevalence of non-HIV related comorbidities, including CKD and CVD. Long-term healthcare management and long-term health outcomes could be improved for PLHIV by: careful HIV management according to current recommendations with optimal selection of antiretrovirals, and early management of comorbidities through recommended lifestyle improvements and preventative measures.


Assuntos
Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Fraturas Ósseas/epidemiologia , Infecções por HIV/epidemiologia , HIV-1/genética , Hipertensão/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Envelhecimento , Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Comorbidade/tendências , Estudos Transversais , Feminino , França/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , RNA Viral/análise , Fatores de Risco
3.
Rev Med Interne ; 40(1): 47-51, 2019 Jan.
Artigo em Francês | MEDLINE | ID: mdl-30093106

RESUMO

In June 2016, 8124 medical students in their sixth year of graduation passed the first computerized national ranking exam (CNRE) in France after which they will have to choose what medical specialty they will be practicing all their life. We conducted the first educational assessment of this CNRE according to two criteria: the relevance of the questions and the cognitive domain mainly required to answer these questions. We propose two improvements for the future CNRE: promote student reasoning in the multiple choices questions, reduce to 10 the number of multiple choice questions in the progressive clinical cases and increase by 9 their total number (from 18 to 27), and use a majority of mini-clinical cases for isolated multiple choice questions in order to focus students on reasoning instead of simple knowledge restitution.


Assuntos
Educação Médica/métodos , Avaliação Educacional/métodos , França , Humanos , Medicina , Melhoria de Qualidade , Estudantes de Medicina
4.
J Clin Virol ; 104: 56-60, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29738895

RESUMO

BACKGROUND: Enterovirus (EV) meningitis is the most common form of meningitis. Clinical and biological manifestations may be non-specific, leading to prolonged and costly investigations. OBJECTIVES: To determine the different aspects of EV meningitis and the variables associated with length of stay (LOS) in hospital independently of patients' age. STUDY DESIGN: Single center retrospective study of all EV PCR positive CSF samples during 3.5 years in Bordeaux University Hospital, France. RESULTS: 172 patients were included. 65 were under 3 years old and 49 over 18 years old. 10% of patients had severe forms of the disease. 47 patients (27.3%) had normal CSF count and in 63 patients (36.6%) polynuclear cells predominated in CSF. Procalcitonin, Hoens' score or PCR in stool samples appeared as good markers for enteroviral diagnosis. Time elapsed before PCR results was associated with LOS (p = .002) and should help in limiting investigations in case of aseptic meningitis. CONCLUSION: Rapid availability of EV PCR reduces LOS for patients and contributes to diminish unnecessary procedures and further tests.


Assuntos
Infecções por Enterovirus/patologia , Meningite Viral/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Líquido Cefalorraquidiano/virologia , Criança , Pré-Escolar , Enterovirus/isolamento & purificação , Fezes/virologia , Feminino , França , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Pró-Calcitonina/análise , Estudos Retrospectivos , Adulto Jovem
5.
HIV Med ; 19(3): 227-237, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29214737

RESUMO

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.


Assuntos
Benzimidazóis/administração & dosagem , Coinfecção/tratamento farmacológico , Fluorenos/administração & dosagem , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Sofosbuvir/administração & dosagem , Idoso , Benzimidazóis/efeitos adversos , Esquema de Medicação , Feminino , Fibrose , Fluorenos/efeitos adversos , Genótipo , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , Hepacivirus/genética , Hepatite C Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Resultado do Tratamento
6.
Med Mal Infect ; 47(7): 470-476, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28943166

RESUMO

OBJECTIVE: To explore knowledge on syphilis, sexual behaviors, and attitudes in men living with HIV in southwestern France. PATIENTS AND METHODS: In the ANRS CO3 Aquitaine Cohort of people living with HIV (PLHIV), a self-administered questionnaire was proposed to all male PLHIV attending one of the seven participating clinics between September 22 and October 24, 2014. The 15 questions explored patient knowledge about syphilis disease, attitudes, and behaviors during sexual intercourse. RESULTS: Among 302 patients surveyed, 101 reported at least one episode of syphilis. A history of syphilis was associated with awareness that syphilis was on the rise in men who have sex with men (MSM) in the Aquitaine region (46% vs. 22%, P<0.0001). Knowledge that syphilis could be transmitted by oral sex was low in both patients with (37%) and without (20%) a history of syphilis (P=0.0045). Patients with a history of syphilis more often used recreational drugs (RR 1.6; P=0.0028). Among 160 patients who had sexual intercourse with a man in the past 12 months, 23% reported using condoms for oral intercourse and 80% reported using condoms for anal intercourse. Sixty-two per cent of MSM declared being ready to change their practice if informed about the rise in syphilis. CONCLUSIONS: This survey revealed important information gaps in PLHIV about syphilis and related behavior. The reported receptiveness of this population to behavioral change may help inform educational interventions.


Assuntos
Infecções por HIV/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Sífilis/psicologia , Adulto , Preservativos/estatística & dados numéricos , França/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Drogas Ilícitas , Comportamento de Busca de Informação , Masculino , Pessoa de Meia-Idade , Assunção de Riscos , Autorrelato , Comportamento Sexual , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Inquéritos e Questionários , Sífilis/epidemiologia , Sífilis/transmissão , Sexo sem Proteção
7.
HIV Med ; 17(10): 758-765, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27187027

RESUMO

OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.


Assuntos
Coinfecção/complicações , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Transtornos Mentais/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
8.
J Clin Virol ; 73: 32-35, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26528903

RESUMO

BACKGROUND: As first generation HCV-specific protease inhibitors, boceprevir (BOC) or telaprevir (TVR) can achieve 60% to 70% sustained virological response (SVR) for HCV infected patients with genotype 1 infections, they could remain temporary a therapeutic option in patients living in resources limited countries with limited access to the new anti-HCV direct acting antiviral (DAA) drugs, such as sofosbuvir. OBJECTIVES AND STUDY DESIGN: Here we evaluated in a routine practice setting, the treatment responses, tolerance and factors associated with SVR of a triple therapy with BOC or TVR, combined with pegylated interferon and ribavirin (PegIFN/RBV) in HIV/HCV co-infected patients, included in a large cohort of HIV/HCV coinfected patients (ANRS CO13-HEPAVIH). RESULTS: Among the 89 HIV/HCV coinfected patients treated, 65% of whom were previous non-responders to PegIFN/RBV therapy, 65%, 55% and 41% had at baseline genotype 1a, a high baseline HCV-RNA (≥800,000 IU/ml) and a cirrhosis, respectively. The SVR12 rate was 63% overall, 53% for BOC-based regimen and 66% for TVR-based regimen. In multivariate analysis, two factors were significantly associated with HCV SVR: HCV viral load <800,000 IU/mL at treatment initiation versus ≥800,000 IU/mL (OR 4.403, 95% CI 1.29-15.04; p=0.018) and virological response at W4 (HCV-RNA undetectable after 4 weeks of triple therapy) (OR 3.35, 95% CI 1.07-10.48; p=0.038). CONCLUSIONS: Overall SVR12 was 63% and our results suggest that HIV/HCV coinfected patients with low HCV viral load (<800,000 IU/mL) and undetectable HCV-RNA after 4 weeks of triple therapy with TVR or BOC-based regimen have a higher probability of treatment success.


Assuntos
Antivirais/administração & dosagem , Infecções por HIV/tratamento farmacológico , Hepacivirus/fisiologia , Hepatite C/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Prolina/análogos & derivados , Antivirais/farmacologia , Coinfecção/tratamento farmacológico , Coinfecção/virologia , Feminino , Infecções por HIV/virologia , Hepacivirus/efeitos dos fármacos , Hepatite C/virologia , Humanos , Interferons/administração & dosagem , Interferons/farmacologia , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/farmacologia , Prolina/administração & dosagem , Prolina/farmacologia , Ribavirina/administração & dosagem , Ribavirina/farmacologia , Resultado do Tratamento , Carga Viral/efeitos dos fármacos
9.
Med Mal Infect ; 44(11-12): 502-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25391635

RESUMO

OBJECTIVE: We report the features and diagnosis of complicated mumps in previously vaccinated young adults. PATIENTS AND METHODS: We retrospectively studied 7 cases of complicated mumps managed during 1 year at the Bordeaux University Hospital. The diagnosis was suggested by the clinical presentation and confirmed using specific RT-PCR. RESULTS: Five cases of meningitis, 1 of orchitis, and 1 of unilateral hearing impairment were identified. Each of the 7 patients had been previously vaccinated with MMR, 4 had received 2 doses of this vaccine. Blood tests revealed high rates of IgG antibodies, usually considered as sufficient for immunological protection, and every patient had at least 1 positive RT-PCR test for mumps. CONCLUSION: Outbreaks of complicated mumps may still occur despite a broad coverage of MMR vaccination. The clinical presentation suggested mumps but the final diagnosis could only be confirmed by genomic detection of the virus. Unusual viral strains with increased neurovirulence, insufficient population coverage associated with immunity decrease over time may explain outbreaks of complicated mumps. A full vaccine scheme of contact people or a third injection of vaccine for previously vaccinated people who are at risk of developing mumps are required to prevent further spreading of the disease during the outbreak.


Assuntos
Surtos de Doenças , Vacina contra Sarampo-Caxumba-Rubéola , Meningite Viral/epidemiologia , Caxumba/epidemiologia , Orquite/epidemiologia , Vacinação , Adolescente , Adulto , Anticorpos Antivirais/sangue , Feminino , França/epidemiologia , Perda Auditiva Unilateral/epidemiologia , Perda Auditiva Unilateral/virologia , Humanos , Imunização Secundária , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Meningite Viral/virologia , Caxumba/líquido cefalorraquidiano , Caxumba/diagnóstico , Caxumba/virologia , Vírus da Caxumba/imunologia , Vírus da Caxumba/isolamento & purificação , Orquite/virologia , Estudos Retrospectivos , Risco , Potência de Vacina , Adulto Jovem
10.
HIV Med ; 14(7): 430-6, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23461846

RESUMO

OBJECTIVES: Many HIV-infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti-HIV therapy. The aim of this study was to identify factors influencing guideline-based HCV treatment initiation in a large cohort of HIV/HCV-coinfected patients. METHODS: Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score >F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (<800000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow-up and those who did not. RESULTS: In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation [odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17-4.81; P=0.017], whereas patients with children (OR 0.53; 95% CI 0.30-0.91; P=0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01-0.78; P=0.03) were less likely to be treated. CONCLUSIONS: Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti-HCV therapy in this population.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/uso terapêutico , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Coinfecção , Comorbidade , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon-alfa/uso terapêutico , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cooperação do Paciente , Guias de Prática Clínica como Assunto , Ribavirina/uso terapêutico , Adulto Jovem
11.
J Viral Hepat ; 18(7): e307-14, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21692942

RESUMO

The impact of antiretroviral drug exposure and associated lipodystrophy and/or insulin resistance (IR) on advanced liver fibrosis in HIV/HCV-coinfected patients is not fully documented. We determined the prevalence of advanced liver fibrosis (defined by hepatic stiffness ≥9.5 kPa) and associated factors, focusing on the impact of highly active antiretroviral therapy and its major adverse effects (lipodystrophy and IR), in 671 HIV/HCV-coinfected patients included in the ANRS CO13 HEPAVIH cohort. One hundred ninety patients (28.3%) had advanced liver fibrosis. In univariate analysis, advanced liver fibrosis was significantly associated with male sex, higher body mass index, HCV infection through intravenous drug use, a lower absolute CD4 cell count, a longer history of antiretroviral treatment, longer durations of protease inhibitors, non-nucleoside reverse transcriptase inhibitors and NRTI exposure, lipodystrophy, diabetes, and a high homeostasis model assessment method (HOMA) value. The only antiretroviral drugs associated with advanced liver fibrosis were efavirenz, stavudine and didanosine. In multivariate analysis, male sex (OR 2.0, 95% CI 1.1-3.5; P = 0.018), HCV infection through intravenous drug use (OR 2.0, 95% CI 1.1-3.6; P = 0.018), lipodystrophy (OR 2.0, 95% CI 1.2-3.3; P = 0.01), median didanosine exposure longer than 5 months (OR 1.7, 95% CI 1.0-2.8; P = 0.04) and a high HOMA value (OR 1.1, 95% CI 1.0-1.2; P = 0.005) remained significantly associated with advanced liver fibrosis. Mitochondrial toxicity and IR thus appear to play a key role in liver damage associated with HIV/HCV-coinfection, and this should be taken into account when selecting and optimizing antiretroviral therapy. Antiretroviral drugs with strong mitochondrial toxicity (e.g. didanosine) or a major effect on glucose metabolism should be avoided.


Assuntos
Antivirais/efeitos adversos , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepatite C/tratamento farmacológico , Lipodistrofia/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Adulto , Alcinos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Antivirais/uso terapêutico , Benzoxazinas/efeitos adversos , Benzoxazinas/uso terapêutico , Contagem de Linfócito CD4 , Ciclopropanos , Didanosina/efeitos adversos , Didanosina/uso terapêutico , Feminino , Infecções por HIV/complicações , Hepatite C/complicações , Humanos , Resistência à Insulina , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/efeitos dos fármacos , Fatores Sexuais , Estavudina/efeitos adversos , Estavudina/uso terapêutico
12.
Antimicrob Agents Chemother ; 55(7): 3187-94, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21576445

RESUMO

The HIV-1 integrase (IN) mutations Y143C/R are known as raltegravir (RAL) primary resistance mutations. In a previous study (S. Reigadas et al., PLoS One 5:e10311, 2010), we investigated the genetic pathway and the dynamics of emergence of the Y143C/R mutations in three patients failing RAL-containing regimens. In these patients, the Y143C/R mutation was associated with the T97A mutation. The aim of the present biochemical and molecular studies in vitro was to evaluate whether the secondary mutation, T97A, associated with the Y143C/R mutation could increase the level of resistance to RAL and impact IN activities. Site-directed mutagenesis experiments were performed with expression vectors harboring the region of the pol gene coding for IN. With a 3'-end processing assay, the 50% inhibitory concentrations (IC(50)) were 1.2 µM, 1.2 µM, 2.4 µM (fold change [FC], 2), and 20 µM (FC, 16.7) for IN wild type (WT), the IN T97A mutation, the IN Y143C/T97A mutation, and the IN Y143R/T97A mutation, respectively. FCs of 18 and 100 were observed with the strand transfer assay for IN Y143C/T97A and Y143R/T97A mutations, with IC(50) of 0.625 µM and 2.5 µM, respectively. In the strand transfer assay, the IN Y143C or R mutation combined with the secondary mutation T97A severely impaired susceptibility to RAL compared to results with the IN Y143C or R mutation alone. Assays without RAL suggested that the T97A mutation could rescue the catalytic activity which was impaired by the presence of the Y143C/R mutation. The combination of the T97A mutation with the primary RAL resistance mutations Y143C/R strongly reduces the susceptibility to RAL and rescues the catalytic defect due to the Y143C/R mutation. This result indicates that the emergence of the Y143C/R/T97A double-mutation pattern in patients is a signature of a high resistance level.


Assuntos
Farmacorresistência Viral/genética , Inibidores de Integrase de HIV/farmacologia , Integrase de HIV/química , Integrase de HIV/genética , HIV-1/efeitos dos fármacos , HIV-1/genética , Pirrolidinonas/farmacologia , Humanos , Modelos Moleculares , Mutação , Raltegravir Potássico , Relação Estrutura-Atividade
13.
HIV Med ; 12(8): 506-9, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21410862

RESUMO

OBJECTIVES: Data on the natural selection of isolates harbouring mutations within the NS3 protease, conferring resistance to hepatitis C virus (HCV) protease inhibitors (PIs), are limited for HIV/HCV-coinfected patients. The aim of this study was to describe the natural prevalence of mutations conferring resistance to HCV PIs in HIV/HCV-coinfected patients compared with HCV-monoinfected patients. METHODS: The natural prevalences of HCV PI resistance mutations in 120 sequences from HIV/HCV-coinfected patients (58 genotype 1a, 18 genotype 1b and 44 genotype 4) and 501 sequences from HCV-monoinfected patients (476 genotype 1 and 25 genotype 4), retrieved from GenBank as a control group, were compared. RESULTS: Of 76 sequences from HIV/HCV genotype 1-coinfected patients, six (7.9%) showed amino acid substitutions associated with HCV PI resistance (V36L, n=1; V36M, n=2; T54S, n=2; R155K, n=1). In 31 of 476 (6.5%) HCV genotype 1 sequences retrieved from the GenBank database, HCV PI resistance mutations were found. The difference was not statistically significant (P=0.6). All of the sequences from HIV/HCV genotype 4-coinfected patients and those retrieved from the GenBank database had amino acid changes at position 36 (V36L). CONCLUSION: Our study suggests that the natural prevalence of strains resistant to HCV PIs does not differ between HCV-monoinfected and HIV/HCV-coinfected patients. Further studies on larger cohorts are needed to confirm these findings and to evaluate the impact of these mutations in clinical practice.


Assuntos
Farmacorresistência Viral/genética , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Proteínas não Estruturais Virais/genética , Adulto , Antivirais/uso terapêutico , Coinfecção , Feminino , Genótipo , Hepacivirus/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Peptídeo Hidrolases/genética
14.
Int J STD AIDS ; 22(2): 67-72, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21427426

RESUMO

The aim of the paper is to describe the characteristics of postmenopausal HIV-infected women and to investigate the factors associated with an earlier onset of menopause in a hospital-based cohort. Information was collected using a self-administered questionnaire. A Cox model was used to determine factors associated with menopause. Among the 404 women who completed the questionnaire, 69 were naturally postmenopausal at the time of the study (median age at onset: 49 years, premature menopause <40 years: 12%). The onset of menopause was studied among the 41 women still menstruating at the enrollment in the cohort, and who experienced menopause during follow-up. African origin (hazard ratio [HR] = 8.16; 95% confidence interval [CI] = 2.23-29.89) and history of injecting drug use (IDU) (HR = 2.46; 95% CI = 1.03-5.85) were associated with an increased risk of earlier menopause. Women with a CD4 cell count <200 cells/mm(3) tended to reach menopause earlier (HR = 2.25; 95% CI = 0.94-5.39). Earlier occurrence of menopause seems to be associated with factors already reported in HIV-negative women (IDU, ethnicity) and with HIV-related immunodeficiency.


Assuntos
Infecções por HIV/complicações , Menopausa Precoce , Adulto , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários
15.
HIV Med ; 11(5): 308-17, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20002500

RESUMO

OBJECTIVES: The aims of the present study were to estimate the prevalence of renal impairment (RI) among HIV-infected adult patients and to investigate the associated factors. METHODS: A cross-sectional survey was conducted in a French hospital-based cohort. Clearance of creatinine (CC) was calculated using the Cockcroft-Gault formula. Four stages of RI were defined: mild (60-90 mL/min), moderate (30-60), severe (15-30) and end stage (<15). Logistic regression models were used to investigate factors associated with RI. RESULTS: The male/female ratio of the 2588 patients enrolled was 3:1 and the median age was 42 years. At the time of assessment of CC, the median CD4 count was 430 cells/microL and HIV plasma viral load (VL) was<50 copies/mL in 60%. The overall prevalence of RI was 39.0%: 34.2% mild, 4.4% moderate, 0.3% severe and 0.2% end-stage. Mild RI was associated with female gender [odds ratio (OR)=3.3: 95% CI 2.6-4.3)], age >50 years (OR=9.8: 7.4-13.0) and 40-50 years (OR=1.9: 1.5-2.4), body mass index (BMI) <22 kg/m(2) (OR=3.3: 2.7-4.3) and tenofovir exposure (OR=1.4: 1.0-1.9 for <1 year and OR=1.5: 1.2-2.0 for >1 year). Advanced RI (CC <60 mL/min) was associated with age >50 years (OR=5.6: 2.9-10.9) and 40-50 years (OR=2.2: 1.1-1.4), BMI <22 kg/m(2) (OR=1.5: 1.0-2.4), hypertension (OR=2.5: 1.4-2.5) and indinavir (IDV) exposure >1 year (OR=2.3: 1.5-3.6). CONCLUSION: This survey confirms the high prevalence of RI in HIV-infected patients and indicates the importance of the investigation of renal function especially in women, older patients, those with a low BMI or treated with tenofovir or IDV.


Assuntos
Creatinina/sangue , Infecções por HIV/epidemiologia , Insuficiência Renal/epidemiologia , Adenina/efeitos adversos , Adenina/análogos & derivados , Adulto , Fármacos Anti-HIV/efeitos adversos , Índice de Massa Corporal , Contagem de Linfócito CD4 , Métodos Epidemiológicos , Feminino , França/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Hipertensão/epidemiologia , Indinavir/efeitos adversos , Rim/efeitos dos fármacos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Organofosfonatos/efeitos adversos , Insuficiência Renal/etiologia , Tenofovir
16.
Euro Surveill ; 13(22)2008 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-18761958

RESUMO

Our objective was to estimate the prevalence of HCV and HBV co-infection among HIV-infected adults in France and describe the epidemiological characteristics of co-infected patients and their clinical management. A one-day national cross-sectional survey was conducted in 2004. A random and proportional probability sample design was used, based on the number of AIDS cases reported since 1999 by hospital wards. Weighted estimations were computed. HIV-infected adults (out/in-patients) were included after consent. Data were collected on demographic criteria, HIV, HCV and HBV infections, as well as on antiviral therapies. Overall, 1849 HIV-infected patients were included. The prevalence of anti-HCV or HCV RNA positivity (HCV co-infection) was 24.3% [95% confidence interval (CI): 21.3-27.6] and varied from 3.1% in men who had sex with men to 92.8% in injecting drug users (IDUs). The prevalence of positive HCV RNA was 17.0% [95% CI:14.7-19.4]. The prevalence of HBs antigen (Ag) or HBV DNA positivity was 7.0% [95% CI: 5.9-8.1] and varied with the continent of birth from 2.1% in Northern Africa to 10.8% in sub-Saharan Africa. The prevalence of HIV-HCV-HBV co-infection was 1.6% [95% CI: 1.0-2.4], mostly IDUs (83.3%). A severe liver disease (cirrhosis or hepatocellular carcinoma) was diagnosed in 24.7% of the positive HCV RNA patients. This study confirmed the burden of HCV infection in French HIV-infected patients and described for the first time in France the epidemiological characteristics of HIV-HBV co-infection. Furthermore, it stresses the severity of liver disease related to HCV in HIV-infected population.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Infecções por HIV/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Vigilância da População , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Comorbidade , Feminino , França/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Abuso de Substâncias por Via Intravenosa/epidemiologia
17.
J Viral Hepat ; 15(6): 427-33, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18221303

RESUMO

The recent availability of non-invasive tools to measure liver fibrosis has allowed examination of its extent and determination of predictors in all patients with chronic hepatitis C virus (HCV) infection. On the other hand, most information on hepatic fibrosis in HCV/human immunodeficiency virus (HIV)-coinfected patients has been derived from liver biopsies taken before highly active antiretroviral therapy (HAART) was widely available. All consecutive HCV patients with elevated aminotransferases seen during the last 3 years were evaluated and liver fibrosis measured using transient elastography (FibroScan) and biochemical indexes. Patients were split according to their HIV serostatus. A total of 656 (69.6%) HCV-monoinfected and 287 (30.4%) HIV/HCV-coinfected patients were assessed. Mean CD4 count of coinfected patients was 493 cells/muL and 88% were under HAART (mean time, 4.2 +/- 2.4 years). Advanced liver fibrosis or cirrhosis was recognized in 39% of the coinfected and 18% of the monoinfected patients (P < 0.005). A good correlation was found between FibroScan) and biochemical indexes [AST to platelet ratio index (r = 0.405, P < 0.0001), FIB-4 (r = 0.393, P < 0.0001) and Forns (r = 0.407, P < 0.0001)], regardless of the HIV status. In the multivariate analysis, age >45 years, body mass index (BMI) >25 kg/m(2), and HIV infection were independently associated with advanced liver fibrosis or cirrhosis. HIV/HCV-coinfected patients have more advanced liver fibrosis than HCV-monoinfected patients despite the immunologic benefit of HAART.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/etiologia , Adulto , Idoso , Índice de Massa Corporal , Técnicas de Imagem por Elasticidade , Feminino , Infecções por HIV/tratamento farmacológico , Soronegatividade para HIV , Soropositividade para HIV/complicações , Hepatite C Crônica/diagnóstico por imagem , Humanos , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada
18.
Aliment Pharmacol Ther ; 26(11-12): 1489-98, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17903235

RESUMO

BACKGROUND: Significance of steatosis in HIV-HCV coinfection remains controversial. AIM: To compare the prevalence and predictors of hepatic steatosis between HIV-HCV and HCV patients matched for steatosis known determinants. METHODS: A total of 564 HCV-naive patients undergoing liver biopsy were studied: 137 with HIV-HCV coinfection and 427 with HCV monoinfection, among whom 137 were matched for age, gender, body mass index and HCV genotype. RESULTS: Steatosis of any grade (67.1% vs. 41.6%, P < 0.0001), mixed steatosis (55.4% vs. 21.1%, P < 0.0001), severe histological activity (A2-A3: 78.1% vs. 55.5%, P < 0.0001) and severe fibrosis (F3-F4: 33.1% vs. 15.3%, P < 0.0001) were significantly more common in coinfected than in matched monoinfected patients. In multivariate analysis, steatosis was associated only with severe histological activity [odds ratio (OR): 3.1 (95% CI: 1.3-7.1)] in coinfected patients and with elevated body mass index [OR; 1.3 (1.1-1.5)], HCV genotype 3 [OR: 5.6 (2.3-13.9)], severe histological activity [OR: 3.1 (1.3-7.3)] and severe fibrosis [OR: 4.7 (1.3-17.3)] in monoinfected patients. CONCLUSIONS: Steatosis is significantly more common and severe in HIV-HCV coinfected than in HCV monoinfected French patients, even after matching for body mass index and HCV genotype. Steatosis is associated only with severe histological activity in coinfected patients and with previously reported factors in monoinfected patients, thus suggesting different underlying mechanisms.


Assuntos
Índice de Massa Corporal , Fígado Gorduroso/etiologia , Infecções por HIV/complicações , Hepacivirus/classificação , Hepatite C Crônica/complicações , Adulto , Fígado Gorduroso/epidemiologia , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
20.
Med Mal Infect ; 36(9): 473-5, 2006 Sep.
Artigo em Francês | MEDLINE | ID: mdl-17027214

RESUMO

BACKGROUND: Severe community acquired pneumonia is a common cause of acute respiratory failure. The influenza virus itself can cause a severe pneumonia and non-respiratory illness. CASE REPORT: A physician developed an acute respiratory failure associated with hemolytic anemia, acute renal failure, and myocarditis. Influenza A infection was diagnosed by screening for antibodies (complement fixation, ELISA Ig A). DISCUSSION: Fulminant influenza pneumonia is a rare clinical presentation of influenza infection and usually has a severe clinical course. Influenza infection is also associated with myositis, myocarditis, acute renal failure, encephalopathy, and hemolytic anemia. Rapid laboratary diagnosis can be made by PCR or immunofluorescence applied directly to respiratory specimens. Antiviral treatment did not prove its efficacy in fulminant Influenza. This case report is an opportunity to stress the importance of seroprophylaxis by parenteral vaccination in exposed occupations.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Influenza Humana/complicações , Pneumonia Viral/diagnóstico , Humanos , Vacinas contra Influenza , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/prevenção & controle
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