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 TratamentoRESUMO
The purpose of this investigation was to evaluate the microbiological diagnosis yield of post-biopsy blood cultures (PBBCs) and second percutaneous needle biopsy (PNB) following an initial negative biopsy in vertebral osteomyelitis (VO) without bacteremia. A retrospective multicenter study was performed. Patients with VO, pre-biopsy negative blood culture(s), ≥1 PNB, and ≥1 PBBC (0-4 h) were included. One hundred and sixty-nine PNBs (136 first and 33 following initial negative biopsy) were performed for 136 patients (median age = 58 years, sex ratio M/F = 1.9). First and second PNBs had a similar yield: 43.4 % (59/136) versus 39.4 % (13/33), respectively. Only two PBBCs (1.1 %) led to a microbiological diagnosis. The strategy with positive first PNB and second PNB following an initial negative result led to microbiological diagnosis in 79.6 % (74/93) of cases versus 44.1 % (60/136) for the strategy with only one biopsy. In the multivariate analysis, young age (odds ratio, OR [95 % confidence interval (CI)] = 0.98 [0.97; 0.99] per 1 year increase, p = 0.02) and >1 sample (OR = 2.4 ([1.3; 4.4], p = 0.007)) were independently associated with positive PNB. To optimize microbiological diagnosis in vertebral osteomyelitis, performing a second PNB (after an initial negative biopsy) could lead to a microbiological diagnosis in nearly 80 % of patients. PBBC appears to be limited in microbiological diagnosis.
Assuntos
Osteomielite/diagnóstico , Doenças da Coluna Vertebral/diagnóstico , Idoso , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Bacteriemia/patologia , Biópsia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/microbiologia , Osteomielite/patologia , Estudos Retrospectivos , Doenças da Coluna Vertebral/microbiologia , Doenças da Coluna Vertebral/patologiaRESUMO
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/genéticaRESUMO
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 , TenofovirAssuntos
Doenças Mamárias/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Úlcera Cutânea/diagnóstico , Tuberculose Cutânea/diagnóstico , Adolescente , Doenças Mamárias/tratamento farmacológico , Doenças Mamárias/microbiologia , Doenças Mamárias/patologia , Contagem de Colônia Microbiana , Diagnóstico Diferencial , Feminino , Humanos , Úlcera Cutânea/tratamento farmacológico , Úlcera Cutânea/microbiologia , Úlcera Cutânea/patologia , Tuberculose Cutânea/tratamento farmacológico , Tuberculose Cutânea/microbiologia , Tuberculose Cutânea/patologiaRESUMO
We observed a prolonged shedding of virus 14 and 28 days after symptom onset in two patients with pandemic H1N1 influenza, who did not have immunodepression and were treated with neuraminidase inhibitor. This prolonged shedding was not associated with the emergence of resistance mutation H275Y in the viral neuraminidase gene.
Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/diagnóstico , Influenza Humana/transmissão , Eliminação de Partículas Virais , Feminino , França , Humanos , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
UNLABELLED: Studies have shown similar clinical cure rates and shorter length of hospitalization when using linezolid compared to vancomycin in patients with complicated skin and soft-tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). OBJECTIVE: This study had for aim to compare the cost-effectiveness of linezolid versus vancomycin in French healthcare settings. METHOD: A decision-analytic model followed an average patient from the initiation of an empiric treatment until cure, death or second-line treatment failure. A clinical data probability was obtained from clinical trials, resource utilization data (including treatment duration and length of hospitalization) and prevalence of MRSA was obtained from a Delphi panel, and costs from published sources. RESULTS: First-line cure rate for linezolid-treated patients was 90.7% versus 85.5% for vancomycin; the total cure rates after two lines of treatment were 98.5% and 98.0%, respectively. The average total cost was 7,778euro for linezolid versus 8,777euro for vancomycin. The mean estimated length of hospitalization after two lines of treatment was 10.7 days for linezolid versus 13.3 days for vancomycin. The increased effectiveness and reduced cost lead to more frequent prescription. This did not change after one-way sensitivity analyses. CONCLUSION: Linezolid may be considered as a cost-effective treatment for patients with complicated skin and soft-tissue infections suspected to be MRSA related in France.
Assuntos
Acetamidas/uso terapêutico , Anti-Infecciosos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina , Oxazolidinonas/uso terapêutico , Dermatopatias Infecciosas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Acetamidas/economia , Antibacterianos/economia , Antibacterianos/uso terapêutico , Anti-Infecciosos/economia , Árvores de Decisões , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/normas , França , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/economia , Humanos , Pacientes Internados , Linezolida , Oxazolidinonas/economia , Infecções Estafilocócicas/economia , Infecções Cutâneas Estafilocócicas/economiaRESUMO
UNLABELLED: Management of febrile neutropenic patients is described in guidelines. Each cancer center can adapt these according to its local bacterial ecology. We present a retrospective study made in a cancer center from 2001 to 2003. METHOD: Three hundred and fifteen febrile neutropenic episodes after chemotherapy (66% for solid tumor) were analysed. RESULTS: For 279 episodes, no antibiotic therapy was given before admission. Clinical or radiological manifestations occurred in 46%; microbiologically documented infections by hemocultures in 28% (Gram positive: 42%; Gram negative: 51%) and by puncture in 14% (Gram negative: 58%). The length of pyrexia was inferior to 7 days in 88% and neutropenia inferior 7 days in 80.8%. 79.7% of episodes were treated with one of the three antibiotic therapy recommended by the center (ceftriaxone+tobramycin; ceftriaxone+ciprofloxacin; ceftriaxone+ofloxacin); 13.3% were treated with an other therapy; 7% received no antibiotic therapy. 68.5% of patients treated with one of the three antibiotic therapies, became afebrile without changing the antibiotic protocol. CONCLUSION: In our study, there were a majority of Gram negative bacteria except for Pseudomonas aeruginosa. The three antibiotic therapy recommended by the center (third generation cephalosporin+aminoglycosides or fluoroquinolones) were effective and glycopeptide was not necessary in first intention treatment.
Assuntos
Febre/epidemiologia , Neoplasias/complicações , Neutropenia/epidemiologia , Antibacterianos/uso terapêutico , Antineoplásicos/efeitos adversos , Quimioterapia Combinada , Febre/tratamento farmacológico , Febre/etiologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/epidemiologia , Humanos , Neoplasias/tratamento farmacológico , Neutropenia/tratamento farmacológico , Neutropenia/etiologia , Estudos RetrospectivosRESUMO
INTRODUCTION: Periprosthetic knee infection is a severe complication. Confirmed criteria are lacking to choose between one-stage or two-stage prosthesis replacement to treat the infection. The one-stage replacement could lead to a satisfactory control of the infection and to better functional results. METHOD: Retrospective study conducted between January 1, 2009 and December 31, 2014. The objectives of this study were to compare the infection outcome and functional results between the one-stage and two-stage replacement procedures. Functional results were evaluated using the IKS score, KOOS score, and SF-12 quality of life score. RESULTS: Forty-one patients underwent a two-stage replacement procedure and 21 patients a one-stage replacement. The average follow-up was 22 months after surgery. The infection was cured in 78% of patients who underwent a two-stage replacement and 90% of patients who underwent a one-stage replacement (P=0.3). The flexion range of motion was significantly better in the one-stage group than in the two-stage group (P=0.04). Results of the IKS score and of the KOOS score were better in the one-stage group. No difference was observed for the SF-12 score. CONCLUSION: The one-stage replacement procedure for periprosthetic knee infection was associated with a similar healing frequency as the two-stage replacement procedure, and with better knee function.
Assuntos
Artroplastia do Joelho/métodos , Prótese do Joelho/efeitos adversos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos RetrospectivosRESUMO
The objectives of this study were to evaluate the diagnostic value of 99mTc-HMPAO labelled white blood cell scintigraphy (WBCS) in patients with suspected osteomyelitis using late images and to study interobserver reproducibility. This study prospectively included 120 patients, and after a follow-up of one year, only 70 patients (n = 49 with implants, n = 21 without implants) were selected. The final diagnosis of infection was based either on microbiological data (n = 54) or follow-up (n = 16). We performed WBCS with 4 h and 24 h scans. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 77%, 72%, 83%, 64%, and 75% at 4 h, and 74%, 87%, 91%, 59%, and 79% at 24 h, respectively. The interobserver reproducibility shows a 63% prevalence of agreement between results (kappa = 0.5) at 4 h and 80% (kappa = 0.74) at 24 h, respectively. WBCS with 24-h images improves specificity and interobserver reproducibility in patients with suspected osteoarticular sepsis.
Assuntos
Leucócitos/diagnóstico por imagem , Leucócitos/metabolismo , Osteoartrite/diagnóstico , Cintilografia/métodos , Tecnécio Tc 99m Exametazima/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: The aim of the study was to estimate the prescription and administration of antibioprophylaxis for hip and knee replacement in Aquitaine (SouthWestern France). METHODS: In 2003, "Social Security" medical experts performed a descriptive and retrospective study on a sample of scheduled surgical operations in all the Aquitaine public and private hospitals. Antibioprophylaxis, protocols, and practice were assessed by studying the patients' medical files. The analysis was made on adjusted numbers to take into account the size of every institution. RESULTS: In 51 hospitals, 58.8% of antibioprophylaxis protocols followed French guidelines. The sample corresponded to an adjusted number of 9,651 patients. Antibiopropylaxis was prescribed for 99.3% of patients, the course of antibioprophylaxis followed guidelines for 77.4% of the patients, the choice of the molecule and the dosage in 85.4% of the cases. Interval between antibiotic injection and surgical section was the main criterion of nonconformity (56.3%); it was under30 minutes for 43.7% of cephalosporin injections. In the post-operative period, administration complied with the medical prescription for 76.4% of the patients and dosage was adapted for 60.0% of the patients. According to the studied variables, 3 to 23.5% of data was missing in the medical files. CONCLUSION: If the quality of care and practice must be improved, it is mandatory to implement written and confirmed antibioprophylaxis protocols, to better document medical files, to insure an improved coordination among professionals before, during, and after surgery.
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Infecção da Ferida Cirúrgica/prevenção & controle , Antibioticoprofilaxia/normas , França , Humanos , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , População Rural , População UrbanaRESUMO
Relapse after treatment of a spinal infection is infrequent and difficult to diagnose. The aim of this study was to assess the diagnostic performance of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this setting. Thirty patients (21 men, nine women; median age 61.2 years) with a suspected spinal infection relapse were prospectively included between March 2010 and June 2013. The initial diagnosis of spinal infection was confirmed by positive bacterial cultures. The patients underwent [(18)F]FDG PET/CT and magnetic resonance imaging (MRI) 1 month after antibiotic treatment interruption. PET/CT data were interpreted both visually and semi-quantitatively (SUVmax). The patients were followed for ≥12 months and the final diagnosis of relapse was based on new microbiological cultures. Seven patients relapsed during follow up. Sensitivity, specificity, positive predictive value and negative predictive value were 66.6%, 61.9%, 33.3% and 86.6%, respectively for MRI and 85.7, 82.6, 60.0 and 95.0 for PET/CT. Although these values were higher for PET/CT than for MRI, the difference was not statistically significant (p=0.3). [(18)F]FDG PET/CT may be useful for diagnosing a relapse of spinal infections, in particular if metallic implants limit the performance of MRI.
Assuntos
Fluordesoxiglucose F18/administração & dosagem , Meningite/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Doenças da Coluna Vertebral/diagnóstico por imagem , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Sensibilidade e EspecificidadeRESUMO
The spread of multiresistant Staphylococcus and Enterococcus strains required the development of new drugs. Linezolid is the first molecule of a new antibiotic family, oxazolidinones, with an original mechanism of action. In this general review, the authors first present its antibacterial activity, its pharmacokinetic properties, its therapeutic uses in serious Gram-positive infections, pneumonia, skin and soft tissue infections, and also in other indications. They then explain the rules for administration and tolerability.
Assuntos
Acetamidas/uso terapêutico , Anti-Infecciosos/uso terapêutico , Enterococcus/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Oxazolidinonas/uso terapêutico , Inibidores da Síntese de Proteínas/uso terapêutico , Staphylococcus/efeitos dos fármacos , Acetamidas/farmacocinética , Anti-Infecciosos/farmacocinética , Humanos , Linezolida , Oxazolidinonas/farmacocinética , Inibidores da Síntese de Proteínas/farmacocinéticaRESUMO
A hospital-based surveillance of HIV infection was implemented in the Bordeaux Regional University Hospital (France). This reporting system, initiated by the Groupe d'Epidemiologie Clinique du SIDA en Aquitaine, identified and followed-up 89 adult patients with transfusion-associated HIV-1 infection (7.2% of all reported cases). Contamination occurred between August 1981 and June 1985 and diagnosis was made between 1985 and 1989. By 30 June 1990, 43 patients (48.3%) had full-blown AIDS, and 28 of them had died. The mean follow-up period was 66 months (s.d. 16 months). The mean incubation period, i.e. The time interval between the contaminating transfusion and the development of full-blown AIDS, was 62 months [median 73 months; 95% confidence interval (CI) 66-82 months]. Five years after contamination, the cumulative probability of reaching the AIDS stage was 34.2% (95% CI 20.3-49.3%), and the probability of survival was 81.7% (95% CI 72.5-90.0%). From this surveillance system we estimate that in south-western France at the end of 1989 the cumulative incidence of transfusion-associated HIV-1 infection was at least 126 cases (45.6 per million inhabitants). Although we anticipate an increase in transfusion-associated AIDS cases over the next 5 years, there have been no reports of contamination after 1 August 1985, when systematic screening of HIV antibodies was implemented in French blood banks. This confirms the efficacy of screening in countries like France where the risk of contamination through blood products is now minimal.
Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Transfusão de Sangue , Infecções por HIV/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , França/epidemiologia , Infecções por HIV/transmissão , Humanos , Incidência , Masculino , Vigilância da População , Fatores de TempoRESUMO
OBJECTIVES: To assess the temporal trends in incidence of tuberculosis (TB) in HIV-infected patients, to evaluate the impact of pulmonary TB on the Centers for Disease Control and Prevention (CDC) 1993 AIDS case definition and to assess the frequency of Mycobacterium tuberculosis strain resistance. DESIGN: A retrospective study within a cohort. SETTING: The Bordeaux University Hospital and three general hospitals in Aquitaine, southwest France. SUBJECTS: Since 1985, HIV-infected in- and outpatients aged > 13 years have been included in the Aquitaine cohort. Reported cases of pulmonary and extrapulmonary TB were investigated and records cross-referenced with the files of the TB reference laboratory. RESULTS: As of 30 June 1993, the Aquitaine cohort (3119 patients) accounted for 6409 person-years (PY) of follow-up. TB was diagnosed in 139 patients (average annual incidence, 2.17 per 100 PY) of whom 79 had bacteriological diagnosis, 13 histological diagnosis and 47 clinical and/or radiological diagnosis. Extrapulmonary TB accounted for 40% of the cases. Intravenous drug use was more frequent in the group who developed TB (50%) than in the rest of the cohort (40%) (P = 0.009). There was an increase in the incidence rate of TB in the cohort between 1985 (0.45 per 100 PY) and 1989 (2.67 per 100 PY) and a stabilization around 1.5-2.0 per 100 PY until 1993. Pulmonary TB was estimated to increase the AIDS cumulative incidence by 0.4% when performing a simulation with the 1993 AIDS case definition. Single drug resistance was documented in 3.4% of the cases and a multiple drug resistance in 5.1%. CONCLUSION: TB incidence has stabilized since 1990 in the Aquitaine cohort with a limited increase of the number of AIDS cases (1993 CDC criteria). Drug resistance was rare.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Antituberculosos/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose/epidemiologia , Adulto , Estudos de Coortes , Resistência Microbiana a Medicamentos , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Masculino , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Estudos Retrospectivos , Tuberculose/tratamento farmacológico , Tuberculose/etiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/etiologiaRESUMO
OBJECTIVES: To study the epidemiological trends, clinical patterns, evolution and prognosis of HIV infection in women. DESIGN: Cohort study of 1816 HIV-infected patients. RESULTS: Up to 1 January 1991, 483 (26.6%) of the patients reported to the Groupe d'Epidemiologie Clinique du SIDA en Aquitaine surveillance system were women. The male-to-female ratio has decreased progressively (3.4:1 in 1985; 2.7:1 in 1990) over time. Fifty per cent of HIV-infected women are or have been intravenous drug users (IVDU). The proportion of heterosexually acquired HIV infection increased from 11.6 to 34.6% over the last 5 years; 46.9% of the women infected through heterosexual intercourse reported sexual contacts with male IVDU. Excluding Kaposi's sarcoma, no significant difference was observed between men and women in the overall distribution of AIDS-defining events. The observed trend of a slower progression to AIDS in women, compared with men, disappeared when controlling for prognostic variables. However, female sex significantly enhanced survival after AIDS diagnosis in multivariate analysis (relative risk, 2.7; 95% confidence interval, 1.1-6.2). CONCLUSION: Early diagnosis of HIV infection in female patients and prevention of HIV infection among women is now a priority for public health interventions, both in industrialized and in developing countries.
Assuntos
Infecções por HIV/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/etiologia , Adulto , Estudos de Coortes , Demografia , Feminino , França/epidemiologia , Infecções por HIV/etiologia , Humanos , Masculino , Análise Multivariada , Prognóstico , Fatores Sexuais , Doenças Virais Sexualmente Transmissíveis/epidemiologia , Doenças Virais Sexualmente Transmissíveis/transmissão , Abuso de Substâncias por Via Intravenosa/complicações , Fatores de TempoRESUMO
During chronic hepatitis C, hepatitis C virus (HCV) load in plasma was shown to be higher in HIV-co-infected than in immunocompetent patients [1]. The reason for this increased HCV replication is not known. It may be as a result of HIV-induced immune deficiency [2], although some authors did not find any correlation with the CD4 cell count [3]. A direct interaction between HCV and HIV was also hypothesized [4]. Protease inhibitors (PI) used in highly active antiretroviral therapy (HAART) have no HCV reduction effect during the first months of treatment [5-8]. However, a decrease in HCV plasma load was recently described in patients treated with HAART for a year [9,10]. We therefore investigated the potential impact of HAART on intrahepatic HCV load.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Fígado/virologia , Inibidores de Proteases/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Feminino , Hepacivirus/fisiologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , RNA Viral/sangueRESUMO
OBJECTIVE: To study hepatic cytolysis in patients treated by highly active antiretroviral therapy (HAART) with protease inhibitor or with two nucleoside reverse transcriptase inhibitors (NRTIs). METHODS: We selected patients of the Aquitaine Cohort who initiated HAART or two NRTIs before 1 January 1998, had alanine amino-transferase (ALT) < or = 200 IU/I at baseline and at least one follow-up measure. Cox model was used to study the association between occurrence of severe hepatic cytolysis (ALT>200 IU/l) and age, gender, HIV transmission group, baseline CD4 and CD8 cell count, history of hepatic cytolysis, antiretroviral drug, baseline liver enzymes (WHO classification level 0: < or = 50 IU/l, level 1: 51 to 100, level 2: 101 to 200), hepatitis B and C co-infection. RESULTS: Sixty-four of 748 (8.5%) patients treated with HAART and 71 of 1249 (5.7%) treated with two NRTIs developed cytolysis. The probability of occurrence was 7.9% after 1 year [95% confidence interval (CI), 5.9-10.4] for patients treated with HAART and 4.8% (95% CI, 3.6-6.4) for patients treated with two NRTIs (log-rank test, P = 0.01). The median time to occurrence was 164 days for HAART-treated patients and 252 days for those treated with two NRTIs. In multivariate analysis, the history of cytolysis [hazard ratio (HR) = 2.3; 95% CI, 1.2-4.4], baseline value of ALT (HR = 2.4; 95% CI, 1.2-4.8 and HR = 3.3; 95% CI, 1.4-7.4 for levels 1 and 2, respectively), hepatitis B (HR = 3.0; 95% CI, 1.4-6.2) and C co-infections (HR = 3.2; 95% CI, 1.7-6.2) remained significantly associated with the occurrence of severe hepatic cytolysis among HAART-treated patients. History of cytolysis, hepatitis B and C were associated with cytolysis in patients treated with two NRTIs (HR = 14.8, 2.6 and 2.7, respectively). CONCLUSION: Hepatic cytolysis is more frequent among patients treated with HAART than with two NRTIs. Hepatitis B and C are the major risk factors after initiation of HAART or treatment with NRTIs. Co-infections with hepatitis B virus or hepatitis C virus may modify the management of HIV-infected patients treated by HAART.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Infecções por HIV/tratamento farmacológico , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/administração & dosagem , Estudos de Coortes , Quimioterapia Combinada , Feminino , França , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Fatores de RiscoRESUMO
A case-control study was undertaken to determine risk factors for lactic acidosis in human immunodeficiency virus-infected patients treated with nucleoside reverse-transcriptase inhibitors (NRTIs). From May 1996 to June 2000, 9 patients with lactic acidosis (defined as a plasma lactic acid level of >5 mM and plasma pH of <7.38) were identified. Control patients were randomly selected from among a large cohort of patients who initiated a dual NRTI regimen in 1996 or after. Two factors were associated with an increased risk of lactic acidosis: first, a creatinine clearance of <70 mL/min before lactic acidosis (OR, 15.8 [range, 3.0-86.5], P<10(-4)), and, second, a low nadir CD4+ T lymphocyte count before the inception of NRTI therapy (OR, 8.4 [range, 1.2-infinity], P=.03). The total cumulative exposure to NRTIs was not associated with an increased risk of lactic acidosis, nor was the cumulative exposure to any of the 4 NRTIs studied. According to these results, monitoring of creatinine clearance, especially in patients with a low nadir CD4+ T lymphocyte count, could lead to modifications in antiretroviral therapy in order to diminish the risk of occurrence of lactic acidosis.
Assuntos
Acidose Láctica/induzido quimicamente , Infecções por HIV/complicações , Inibidores da Transcriptase Reversa/efeitos adversos , Acidose Láctica/epidemiologia , Adulto , Estudos de Casos e Controles , Didanosina/efeitos adversos , Didanosina/uso terapêutico , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/uso terapêutico , Fatores de Risco , Estavudina/efeitos adversos , Estavudina/uso terapêuticoRESUMO
In a retrospective study, an increase in double-negative (CD3+ CD4- CD8-) (DN) T lymphocytes has been shown to be an independent predictor of disseminated Mycobacterium avium complex (D.MAC) infection in patients with less than 100 CD4+ T cells per mm3. To better characterize this cell expansion, a prospective study was designed. From July 1995 to April 1997, 206 HIV-infected patients with less than 100 CD4+ T cells per mm3 were prospectively followed up and immunophenotyped. The median followup was 1.1 year (+/-0.5 year), and 14 new D.MAC infections were diagnosed among 84 first AIDS-defining events. In univariate and multivariate analyses, D.MAC infections were the only opportunistic infection with a significant increase in DN T-cell percentage (median = 6.6; range = 1.7 to 24.5, P = 0.004) compared with patients without any opportunistic infection. This alteration in T-lymphocyte count could constitute a predictor for D.MAC infection in clinical practice.