RESUMEN
Severe sepsis induces a sustained immune dysfunction associated with poor clinical behavior. In particular, lymphopenia along with increased lymphocyte apoptosis and decreased lymphocyte proliferation, enhanced circulating regulatory T cells (Treg), and the emergence of myeloid-derived suppressor cells (MDSCs) have all been associated with persistent organ dysfunction, secondary infections, and late mortality. The mechanisms involved in MDSC-mediated T cell dysfunction during sepsis share some features with those described in malignancies such as arginine deprivation. We hypothesized that increasing arginine availability would restore T cell function and decrease sepsis-induced immunosuppression. Using a mouse model of sepsis based on cecal ligation and puncture and secondary pneumonia triggered by methicillin-resistant Staphylococcus aureus inoculation, we demonstrated that citrulline administration was more efficient than arginine in increasing arginine plasma levels and restoring T cell mitochondrial function and proliferation while reducing sepsis-induced Treg and MDSC expansion. Because there is no specific therapeutic strategy to restore immune function after sepsis, we believe that our study provides evidence for developing citrulline-based clinical studies in sepsis.
Asunto(s)
Citrulina/farmacología , Mitocondrias/metabolismo , Sepsis/tratamiento farmacológico , Animales , Arginina/deficiencia , Arginina/metabolismo , Disponibilidad Biológica , Citrulina/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Tolerancia Inmunológica/inmunología , Terapia de Inmunosupresión/métodos , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Células Supresoras de Origen Mieloide/inmunología , Sepsis/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T Reguladores/inmunologíaRESUMEN
We report 20 cases of extensively drug-resistant tuberculosis managed in France. Treatment was individualized and included bedaquiline and linezolid for most patients and surgery in 8 patients. At last follow-up (22 months), 19 patients had achieved conversion from positive to negative on culture testing. These promising results of comprehensive management obtained in a small series deserve confirmation.
Asunto(s)
Tuberculosis Extensivamente Resistente a Drogas/epidemiología , Tuberculosis Extensivamente Resistente a Drogas/terapia , Mycobacterium tuberculosis , Adulto , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Terapia Combinada , Tuberculosis Extensivamente Resistente a Drogas/historia , Femenino , Estudios de Seguimiento , Francia/epidemiología , Historia del Siglo XXI , Humanos , Masculino , Mycobacterium tuberculosis/efectos de los fármacos , Resultado del TratamientoRESUMEN
BACKGROUND: Retreatment with pegylated interferon (peg-IFN) and ribavirin (RBV) results in poor sustained virological response (SVR) rates in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. There are limited data regarding the use of telaprevir plus peg-IFN/RBV in this population. METHODS: HIV type 1-infected patients who previously failed ≥12 weeks of peg-IFN/RBV for HCV genotype 1 coinfection were enrolled in a single-arm, phase 2 trial. Patients with cirrhosis and previous null response were excluded. Authorized antiretrovirals were tenofovir, emtricitabine, efavirenz, atazanavir, and raltegravir. All patients received peg-IFN alfa-2a (180 µg/week) plus RBV (1000-1200 mg/day) for 4 weeks, followed by telaprevir (750 mg or 1125 mg every 8 hours with efavirenz) plus peg-IFN/RBV for 12 weeks and peg-IFN/RBV for 32-56 weeks according to virological response at week 8. The primary endpoint was the SVR rate at 24 weeks after the end of treatment (SVR24). RESULTS: Sixty-nine patients started treatment; SVR24 was achieved in 55 (80% [95% confidence interval, 68%-88%). SVR24 was not influenced by baseline fibrosis stage, IL28B genotype, antiretroviral regimen, HCV subtype, CD4 cell count, previous response to HCV treatment, HCV RNA level, or HCV RNA decline at week 4. HCV treatment was discontinued for adverse events (AEs) in 20% of patients, including cutaneous (4%), psychiatric (4%), hematological (6%), and other AEs (6%). Peg-IFN or RBV dose reduction was required in 23% and 43% of patients, respectively. Seventy percent of patients required erythropoietin, blood transfusions, or RBV dose reduction for anemia. Two patients died during the study. No HIV breakthrough was observed. CONCLUSIONS: Despite a high discontinuation rate related to toxicity, a substantial proportion of treatment-experienced HIV-coinfected patients achieved SVR24 with a telaprevir-based regimen. Clinical Trials Registration. NCT01332955.
Asunto(s)
Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Oligopéptidos/uso terapéutico , Polietilenglicoles/uso terapéutico , Ribavirina/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Resultado del TratamientoRESUMEN
The use of biomimetic approaches in the production of inorganic nanostructures is of great interest to the scientific and industrial community due to the relatively moderate physical conditions needed. In this vein, taking cues from silaffin proteins used by unicellular diatoms, several studies have identified peptide candidates for the production of silica nanostructures. In the current article, we study intensively one such silica-precipitating peptide, LKα14 (Ac-LKKLLKLLKKLLKL-c), an amphiphilic lysine/leucine repeat peptide that self-organizes into an α-helical secondary structure under appropriate concentration and buffer conditions. The suggested mechanism of precipitation is that the sequestration of hydrophilic lysines on one side of this helix allows interaction with the negatively charged surface of silica nanoparticles, which in turn can aggregate further into larger structures. To investigate the process, we carry out 1D and 2D solid-state NMR (ssNMR) studies on samples with one or two uniformly (13)C- and (15)N-labeled residues to determine the backbone and side-chain chemical shifts. We also further study the dynamics of two leucine residues in the sequence through (13)C spin-lattice relaxation times (T1) to determine the impact of silica coprecipitation on their mobility. Our results confirm the α-helical secondary structure in both the neat and silica-complexed states of the peptide, and the patterns of chemical shift and relaxation time changes between the two states suggest possible mechanisms of self-aggregation and silica precipitation.
Asunto(s)
Leucina/química , Lisina/química , Péptidos/química , Dióxido de Silicio/química , Interacciones Hidrofóbicas e Hidrofílicas , Espectroscopía de Resonancia MagnéticaRESUMEN
BACKGROUND: It is well established that high adherence to HIV-infected patients on highly active antiretroviral treatment (HAART) is a major determinant of virological and immunologic success. Furthermore, psychosocial research has identified a wide range of adherence factors including patients' subjective beliefs about the effectiveness of HAART. Current statistical approaches, mainly based on the separate identification either of factors associated with treatment effectiveness or of those associated with adherence, fail to properly explore the true relationship between adherence and treatment effectiveness. Adherence behavior may be influenced not only by perceived benefits-which are usually the focus of related studies-but also by objective treatment benefits reflected in biological outcomes. METHODS: Our objective was to assess the bidirectional relationship between adherence and response to treatment among patients enrolled in the ANRS CO8 APROCO-COPILOTE study. We compared a conventional statistical approach based on the separate estimations of an adherence and an effectiveness equation to an econometric approach using a 2-equation simultaneous system based on the same 2 equations. RESULTS: Our results highlight a reciprocal relationship between adherence and treatment effectiveness. After controlling for endogeneity, adherence was positively associated with treatment effectiveness. Furthermore, CD4 count gain after baseline was found to have a positive significant effect on adherence at each observation period. This immunologic parameter was not significant when the adherence equation was estimated separately. In the 2-equation model, the covariances between disturbances of both equations were found to be significant, thus confirming the statistical appropriacy of studying adherence and treatment effectiveness jointly. CONCLUSIONS: Our results, which suggest that positive biological results arising as a result of high adherence levels, in turn reinforce continued adherence and strengthen the argument that patients who do not experience rapid improvement in their immunologic and clinical statuses after HAART initiation should be prioritized when developing adherence support interventions. Furthermore, they invalidate the hypothesis that HAART leads to "false reassurance" among HIV-infected patients.
Asunto(s)
Terapia Antirretroviral Altamente Activa/psicología , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación/psicología , Cumplimiento de la Medicación/estadística & datos numéricos , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Actitud Frente a la Salud , Recuento de Linfocito CD4 , Estudios de Cohortes , Interpretación Estadística de Datos , Depresión/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Económicos , Factores Socioeconómicos , Resultado del TratamientoRESUMEN
In this monocentric study, the median delay between deep brain stimulation implantation and infection was 28 days (range, 8-820). Infections limited to generator (n = 4) required partial hardware removal, whereas infections involving frontal or retroauricular sites (n = 7) required total removal. Surgical samples yielded Staphylococcus aureus (n = 6), Staphylococcus epidermidis (n = 2), Propionibacterium acnes, and Micrococcus species.
Asunto(s)
Infecciones Bacterianas/diagnóstico , Estimulación Encefálica Profunda/efectos adversos , Infección de la Herida Quirúrgica/diagnóstico , Adulto , Anciano , Infecciones Bacterianas/microbiología , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Masculino , Micrococcus/aislamiento & purificación , Persona de Mediana Edad , Propionibacterium acnes/aislamiento & purificación , Staphylococcus/aislamiento & purificación , Infección de la Herida Quirúrgica/microbiología , Tomografía Computarizada por Rayos XRESUMEN
A rapid and specific high-performance liquid chromatography method with UV detection (HPLC-UV) for the simultaneous determination of 12 beta-lactam antibiotics (amoxicillin, cefepime, cefotaxime, ceftazidime, ceftriaxone, cloxacillin, imipenem, meropenem, oxacillin, penicillin G, piperacillin, and ticarcillin) in small samples of human plasma is described. Extraction consisted of protein precipitation by acetonitrile. An Atlantis T3 analytical column with a linear gradient of acetonitrile and a pH 2 phosphoric acid solution was used for separation. Wavelength photodiode array detection was set either at 210 nm, 230 nm, or 298 nm according to the compound. This method is accurate and reproducible (coefficient of variation [CV] < 8%), allowing quantification of beta-lactam plasma levels from 5 to 250 µg/ml without interference with other common drugs. This technique is easy to use in routine therapeutic drug monitoring of beta-lactam antibiotics.
Asunto(s)
Antibacterianos/sangre , Cromatografía Líquida de Alta Presión/métodos , Monitoreo de Drogas/métodos , beta-Lactamas/sangre , Humanos , Sensibilidad y Especificidad , Espectrofotometría UltravioletaRESUMEN
INTRODUCTION: Mitochondrial dysfunction is a classic complication of HIV infection and its treatment and has also been reported in hepatitis C virus (HCV)-infected patients. Little is known about interactions between both viruses on mitochondrial metabolism. METHODS: We performed a cross-sectional study of HCV-infected patients who underwent liver biopsy as part of their routine care. Mitochondrial function was assessed by (a) liver morphological (histology) and functional (spectro-photometry) studies, and (b) serum lactate kinetics, oxygen uptake, and anaerobic threshold measurement during standardized incremental exercise. Three predefined groups of patients were compared. RESULTS: Thirty-eight HCV-infected patients were included: 13 not HIV infected (group 1), 7 with HIV co-infection and low nucleoside reverse transcriptase inhibitor (NRTI) exposure (none over the last 2 years; group 2), and 18 with HIV co-infection and high NRTI exposure (group 3). On liver biopsies, respiratory chain complex IV activity was impaired, at 5 (2-7) nmol/min/mg substrates in group 1, 5 (3-8) in group 2, and 8 (2-13) in group 3 (normal values, 20-56). Maximal power output was diminished and anaerobic threshold occurred earlier in HIV-infected patients, regardless of NRTI exposure. CONCLUSION: HCV has deleterious effects on liver mitochondrial metabolism, notably on respiratory chain complex IV. No significant interaction with HIV was observed.
Asunto(s)
Infecciones por VIH/complicaciones , VIH/aislamiento & purificación , Hepacivirus/aislamiento & purificación , Hepatitis C/complicaciones , Mitocondrias Hepáticas/patología , Adulto , Biopsia , Estudios Transversales , Femenino , Infecciones por VIH/patología , Infecciones por VIH/virología , Hepatitis C/patología , Hepatitis C/virología , Histocitoquímica , Humanos , Lactatos/sangre , Modelos Lineales , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Mitocondrias Hepáticas/metabolismo , Consumo de OxígenoRESUMEN
BACKGROUND & AIMS: We compared 5 non-specific and 2 specific blood tests for liver fibrosis in HCV/HIV co-infection. METHODS: Four hundred and sixty-seven patients were included into derivation (n=183) or validation (n=284) populations. Within these populations, the diagnostic target, significant fibrosis (Metavir F > or = 2), was found in 66% and 72% of the patients, respectively. Two new fibrosis tests, FibroMeter HICV and HICV test, were constructed in the derivation population. RESULTS: Unadjusted AUROCs in the derivation population were: APRI: 0.716, Fib-4: 0.722, Fibrotest: 0.778, Hepascore: 0.779, FibroMeter: 0.783, HICV test: 0.822, FibroMeter HICV: 0.828. AUROCs adjusted on classification and distribution of fibrosis stages in a reference population showed similar values in both populations. FibroMeter, FibroMeter HICV and HICV test had the highest correct classification rates in F0/1 and F3/4 (which account for high predictive values): 77-79% vs. 70-72% in the other tests (p=0.002). Reliable individual diagnosis based on predictive values > or = 90% distinguished three test categories: poorly reliable: Fib-4 (2.4% of patients), APRI (8.9%); moderately reliable: Fibrotest (25.4%), FibroMeter (26.6%), Hepascore (30.2%); acceptably reliable: HICV test (40.2%), FibroMeter HICV (45.6%) (p<10(-3) between tests). FibroMeter HICV classified all patients into four reliable diagnosis intervals (< or =F1, F1+/-1, > or =F1, > or =F2) with an overall accuracy of 93% vs. 79% (p<10(-3)) for a binary diagnosis of significant fibrosis. CONCLUSIONS: Tests designed for HCV infections are less effective in HIV/HCV infections. A specific test, like FibroMeter HICV, was the most interesting test for diagnostic accuracy, correct classification profile, and a reliable diagnosis. With reliable diagnosis intervals, liver biopsy can therefore be avoided in all patients.
Asunto(s)
Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Pruebas Hematológicas/métodos , Hepatitis C/sangre , Hepatitis C/complicaciones , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Adulto , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Biopsia , Comorbilidad , Femenino , Humanos , Hígado/patología , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Protrombina/metabolismo , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , alfa-Macroglobulinas/metabolismoRESUMEN
OBJECTIVES: To assess simplified maintenance regimens containing dual antiretroviral drugs in patients with controlled human immunodeficiency virus type 1 infection. METHODS: A non-inferiority, randomized, multicentre, open-label trial was performed in 24 AIDS clinical centres in France randomizing 143 patients [treated for >or=6 months, plasma viral load (pVL) <50 copies/mL, no prior history of treatment failure] to receive a two-drug regimen [tenofovir disoproxil fumarate (tenofovir DF) and efavirenz] or to maintain a three-drug treatment (tenofovir DF, lamivudine and efavirenz). The main outcome measure was the success rate (percentage of patients with pVL <50 copies/mL without treatment modifications) at week 48. RESULTS: Success rates for the intention-to-treat analysis were 97.2% (70/72) versus 81.7% (58/71) in the three-drug versus two-drug maintenance regimen groups, respectively [difference, 15.5%; upper limit of one-sided 95% confidence interval (CI), 23.7%], and 100% (70/70) versus 90% (54/60) for the per protocol analysis, respectively (difference, 10%; upper limit of one-sided 95% CI, 16.4%), with a non-inferiority margin set at 14%. Three patients from the two-drug group experienced virological failure with selection of efavirenz-associated mutations. Overall, CD4 counts were significantly increased from baseline (median, +24 cells/mm(3); P = 0.007). Four patients discontinued study treatment due to adverse events in the two-drug group and none in the three-drug group. No significant changes in creatinine clearance or phosphataemia were reported. Overall, levels of triglycerides, total and high-density lipoprotein cholesterol were improved; low-density lipoprotein cholesterol was improved only in the three-drug group. CONCLUSIONS: The non-inferiority of the two-drug versus the three-drug regimen was not demonstrated. Lipid parameters improved after switching from twice-daily highly active antiretroviral therapy (HAART) to once-daily tenofovir-based HAART.
Asunto(s)
Adenina/análogos & derivados , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Organofosfonatos/uso terapéutico , Adenina/uso terapéutico , Adulto , Alquinos , Benzoxazinas/uso terapéutico , Recuento de Linfocito CD4 , Ciclopropanos , Femenino , Francia , Humanos , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Tenofovir , Resultado del Tratamiento , Carga ViralAsunto(s)
Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/complicaciones , Inhibidores de la Proteasa del VIH/efectos adversos , Cálculos Renales/inducido químicamente , Oligopéptidos/efectos adversos , Piridinas/efectos adversos , Ritonavir/efectos adversos , Femenino , Humanos , MasculinoRESUMEN
Health-care workers may be exposed to bullous fluid while caring for bullous skin diseases in HIV-infected patients. Given that bullous fluid is a filtrate of plasma, it may be assumed that HIV viral load (VL) in bullous fluid is close to plasma VL. This was documented in a patient who had discontinued antiretroviral therapy because of nevirapine-associated toxic epidermal necrolysis, but no data are available in patients receiving antiretrovirals. An HIV-infected woman was admitted for leg cellulitis with a large bullous lesion. Her plasma HIV RNA had been undetectable for two years under the combination of efavirenz and boosted lopinavir. Bullous fluid analysis revealed undetectable HIV-1 RNA, while efavirenz and lopinavir concentrations were 1.4 and 3.4 microg/mL, respectively. The ratio of bullous fluid/plasma concentrations was 0.74 for efavirenz and 0.26 for lopinavir. These data may help us evaluate the need for antiretroviral prophylaxis after occupational exposure to bullous lesions fluid.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Infecciones por VIH/virología , VIH-1/fisiología , ARN Viral/análisis , Piel/virología , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Piel/química , Carga ViralRESUMEN
OBJECTIVE: To determine antiviral activity, pharmacokinetic properties, and safety of vicriviroc, an orally available CCR5 antagonist, as monotherapy in HIV-infected patients. DESIGN AND METHODS: An ascending, multiple dose, placebo-controlled study randomized within treatment group. Forty-eight HIV-infected individuals were enrolled sequentially to dose groups of vicriviroc: 10, 25 and 50 mg twice a day, and were randomly assigned within group to receive vicriviroc or placebo (16 total patients/group) for 14 days. RESULTS: Significant reductions from baseline HIV RNA after 14 days were achieved in all active treatment groups. Suppression of viral RNA persisted 2-3 days beyond the end of treatment. Reductions of 1.0 log10 HIV RNA or greater were achieved in 45, 77 and 82% of patients in the three groups, respectively. Eighteen, 46 and 45% of subjects achieved declines of 1.5 log10 or greater in HIV RNA in the three groups, respectively. Vicriviroc was rapidly absorbed with a half-life of 28-33 h, supporting once-daily dosing. Pharmacokinetic parameters were dose linear; steady state was achieved by day 12. Two subjects experienced a transient detectable X4-tropic virus. Vicriviroc was well tolerated in all dose groups. The frequency of adverse events was similar in the vicriviroc and placebo groups: 72 and 62%, respectively. The most frequently reported adverse events included headache, pharyngitis, nausea and abdominal pain, which were not dose related. CONCLUSION: Whereas all doses were well tolerated and produced significant declines in plasma HIV RNA, total oral daily doses of 50 or 100 mg vicriviroc monotherapy for 14 days appeared to provide the most potent antiviral effect in this study.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Antagonistas de los Receptores CCR5 , Infecciones por VIH/tratamiento farmacológico , Piperazinas/administración & dosificación , Pirimidinas/administración & dosificación , Administración Oral , Adolescente , Adulto , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/farmacocinética , Recuento de Linfocito CD4 , Esquema de Medicación , Femenino , VIH-1/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Piperazinas/efectos adversos , Piperazinas/farmacocinética , Pirimidinas/efectos adversos , Pirimidinas/farmacocinética , ARN Viral/análisis , ARN Viral/efectos de los fármacos , Resultado del Tratamiento , Tropismo/efectos de los fármacos , Replicación Viral/efectos de los fármacosRESUMEN
The appearance of primary HIV infection ranges from an asymptomatic presentation to a symptomatic illness resembling infectious mononucleosis. Severe unusual presentations include acute myopericarditis, renal failure, and opportunistic infections such as esophageal candidiasis, cytomegalovirus infection, and Pneumocystis jirovecii pneumonia. We report a case of multiple organ failure during primary HIV infection.
Asunto(s)
Infecciones por VIH/complicaciones , VIH/patogenicidad , Insuficiencia Multiorgánica/virología , Viremia/tratamiento farmacológico , Adolescente , Linfocitos T CD4-Positivos/efectos de los fármacos , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , Carga ViralRESUMEN
BACKGROUND: Different approaches using genotypic, pharmacokinetic parameters or combination of both have been recently developed to monitor antiretroviral treatment in HIV-1-infected individuals. Their uses in clinical practice may improve the benefit of protease inhibitor-based salvage therapy while reducing treatment toxicity and emergence of viral resistance. OBJECTIVES: To assess the prediction of genotypic inhibitory quotient (GIQ) using different genotypic drug resistance interpretation's algorithms and lopinavir plasma concentration in PI-experienced patients treated by lopinavir/ritonavir (LPV/r). Genotypic susceptibility score (GSS) was also evaluated. STUDY DESIGN: Forty-seven HIV-1 PI-experienced, but LPV naïve patients were included in a retrospective cohort study. Plasma HIV-1 viral load (VL), CD4 cell count and LPV plasma concentrations were assessed at weeks (W) 12 and 24. Interpretation of baseline resistance genotype was achieved according to four different algorithms and GSS calculated using two expert systems. GIQ was defined as the ratio of LPV concentration to the number of LPV resistance mutations at day 0 (D0) and patients classified by units of GIQ. The end point of the study was the virological response expressed in HIV VL median decrease from D0 to W24. RESULTS: The overall median VL decrease from D0 to W24 was -2.42 log(10)copies/mL and 60% of patients had VL below 400 copies/mL. The LPV mutation score was predictive of response for all algorithms whereas plasma concentrations of LPV were not. Mean VL decrease was greater for higher GIQ classes and difference reached statistical significance at W24. When considering virological response at W24, GSS calculated with ANRS and Stanford system were good predictor scores as areas under the receiver operating characteristics (ROC) curves were 0.76 for both. CONCLUSION: GIQ was found to be a useful drug-monitoring tool which could be helpful in targeting LPV concentrations in order to achieve long-term undetectable viral load, particularly in genotypic resistant patients.
Asunto(s)
Algoritmos , Farmacorresistencia Viral , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/genética , Pirimidinonas/uso terapéutico , Ritonavir/uso terapéutico , Adulto , Anciano , Estudios de Cohortes , Femenino , Genotipo , Infecciones por VIH/sangre , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/sangre , VIH-1/enzimología , Humanos , Lopinavir , Masculino , Persona de Mediana Edad , Pirimidinonas/sangre , Estudios Retrospectivos , Ritonavir/sangre , Sensibilidad y Especificidad , Carga ViralRESUMEN
OBJECTIVE: This study examined the relations between health locus of control (HLOC) beliefs and health-related quality of life (HRQL) in 302 HIV-infected patients enrolled in a French cohort, 44 months (M44) after they began highly active antiretroviral therapy (HAART). METHODS: HLOC beliefs were measured with the Multidimensional Health Locus of Control (MHLOC) scale and HRQL, with the Medical Outcome Study Short-Form Health Survey (MOS-SF-36). RESULTS: Internal HLOC beliefs at the initiation of treatment were associated with both physical HRQL in multivariate analysis, while chance HLOC beliefs on beginning HAART were associated with mental HRQL at M44. CONCLUSION: These findings suggest the importance of considering the psychological characteristics and psychosocial beliefs of patients at the initiation of ARV treatment to optimise the long-term HRQL of HIV-infected patient and to develop adaptive intervention on coping strategies.
Asunto(s)
Actitud Frente a la Salud , Cultura , Infecciones por VIH/sangre , Infecciones por VIH/psicología , Estado de Salud , Control Interno-Externo , Calidad de Vida/psicología , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Antígenos CD4/sangre , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
This study reports six consecutive patients who underwent heart transplantation as salvage treatment for endocarditis (Duke criteria) with extensive perivalvular lesions and end-stage heart failure. The median age was 45 years (range, 24 to 64), and the aortic valve was affected in all patients. Pathogens were Staphylococcus aureus (n = 2), Streptococcus pneumoniae (n = 2), Streptococcus agalactiae (n = 1), or not documented (n = 1). All patients survived, with no relapse, after a median follow-up of 24.5 months. The 10 patients with heart transplantation for endocarditis previously reported also survived (median follow-up, 27.5 months). Heart transplantation may be considered as salvage treatment in selected patients with intractable infective endocarditis.
Asunto(s)
Endocarditis/cirugía , Trasplante de Corazón/métodos , Terapia Recuperativa/métodos , Adolescente , Adulto , Endocarditis/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Staphylococcus aureus/aislamiento & purificación , Streptococcus agalactiae/aislamiento & purificación , Streptococcus pneumoniae/aislamiento & purificación , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Although the role of clinical/biological factors associated with mortality has already been explored in HIV-infected patients on antiretroviral therapy (ART), to date little attention has been given to the potential role of social vulnerability. This study aimed to construct an appropriate measure of social vulnerability and to evaluate whether this measure is predictive of increased mortality risk in ART-treated patients followed up in the ANRS CO8 APROCO-COPILOTE cohort. METHODS: The cohort enrolled 1,281 patients initiating a protease inhibitor-based regimen in 1997-1999. Clinical/laboratory data were collected every 4 months. Self-administered questionnaires collected psycho-social/behavioural characteristics at enrolment (month [M] 0), M4 and every 8-12 months thereafter. A multiple correspondence analysis using education, employment and housing indicators helped construct a composite indicator measuring social vulnerability. The outcome studied was all-cause deaths occurring after M4. The relationship between social vulnerability and mortality, after adjustment for other predictors, was studied using a shared-frailty Cox model, taking into account informative study dropout. RESULTS: Over a median (IQR) follow-up of 7.9 (3.0-11.2) years, 121 deaths occurred among 1,057 eligible patients, corresponding to a mortality rate (95% CI) of 1.64 (1.37, 1.96)/100 person-years. Leading causes of death were non-AIDS defining cancers (n=26), AIDS (n=23) and cardiovascular diseases (n=12). Social vulnerability (HR [95% CI] =1.2 [1.0, 1.5]) was associated with increased mortality risk, after adjustment for other known behavioural and bio-medical predictors. CONCLUSIONS: Social vulnerability remains a major mortality predictor in ART-treated patients. A real need exists for innovative interventions targeting individuals cumulating several sources of social vulnerability, to ensure that social inequalities do not continue to lead to higher mortality.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Adulto , Recuento de Linfocito CD4 , Causas de Muerte , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Francia/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Factores de Riesgo , Encuestas y Cuestionarios , Carga ViralRESUMEN
OBJECTIVE: To assess the impact of different patterns of adherence to highly active antiretroviral therapy (HAART), in particular, the relative impact of early and late adherence, on long-term immuno-virological response in HIV-infected individuals started on a protease inhibitor-containing regimen. DESIGN: Clinical, immuno-virological and self-reported adherence data were collected at 4 (M4), 12 (M12), 20 (M20), 28 (M28) and 36 (M36) months after HAART initiation in the French APROCO cohort. METHODS: A standardized self-administered questionnaire classified patients as non-adherent, moderately or highly adherent at each visit. Stable viral suppression at both M28 to M36, and a CD4 cell increase > 200 between M0 and M36 were used as outcome measures. RESULTS: Of the 582 patients followed regularly through M36, 360 patients had complete adherence data. Although 59.2% were highly adherent at M4, only 25.8% maintained consistent high adherence throughout the follow-up. High adherence at M4 was independently associated with both stable viral suppression at M28-M36 [OR (95% CI): 2.8 (1.4-5.5)] and a CD4 cell increase > 200 during the same period [OR (95% CI): 3.9 (1.7-9.7)]. However, 'moderately adherent' patients between M12 and M36 had the same likelihood [OR (95% CI): 1.9 (1.1-3.2)] as patients who were always high adherent [OR (95% CI): 1.9 (1.1-3.2)] of achieving stable viral load suppression, relative to those who reported non-adherence episodes. CONCLUSION: Optimizing adherence in the early months of treatment is crucial to ensure long-term immuno-virological high adherence during follow-up have a less negative impact. Priority should be given to interventions aimed to improve adherence in the early months of HAART.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Terapia Antirretroviral Altamente Activa , VIH-1 , Cooperación del Paciente , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/virología , Adulto , Recuento de Linfocito CD4 , Relación CD4-CD8 , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Factores de TiempoRESUMEN
This was a prospective pilot study evaluating a saquinavir (SQV) soft-gel capsules (SGC)/ritonavir (RTV)-containing once-daily regimen over a follow-up of 3 months. The primary end-point was to determine the number of patients both remaining on treatment at month 3 and with trough SQV plasma concentration 24 h after the last intake (C24h) exceeding the inhibition of 95% of viral replication in vitro (IC95). The secondary end-points were to investigate the immuno-virological efficacy and safety of SQV-SGC/RTV once daily, and to explore SQV concentrations in peripheral blood mononuclear cells (PBMCs). Twenty-three antiretroviral-naive and 17 protease inhibitors (PIs) experienced HIV-1-infected patients with plasma HIV-1 RNA level below 200 copies/ml were enrolled. They were assigned to SQV-SGC/RTV (1600/100 mg once daily) combined with nucleoside and/or non-nucleoside reverse transcriptase inhibitors. In a subgroup of 13 patients, both plasma and intracellular SQV concentrations were determined. By intent to treat analysis the percentage of success at month 3 was 87.5% (confidence interval: 73.2-95.8%) with 78.3% in naive and 100% in PI-experienced patients. SQV C24h and intracellular concentrations [median (range, n)] were 241 ng/ml (40-1209, 35) and 323 ng/ml (168-475, 12), respectively. Intracellular concentrations showed an accumulation of SQV in PBMCs persisting during 24 h. Neither immunological nor virological failure was observed. Clinical and biological tolerance was acceptable in all patients but three with adverse effects leading to discontinuation. These data confirmed the short-term efficacy of SQV-SGC/RTV once-daily regimen based on SQV therapeutic drug monitoring.