RESUMEN
Despite long-term successful treatment with cART, impairments in cognitive functioning are still being reported in HIV-infected patients. Since changes in cognitive function may be preceded by subtle changes in brain function, neuroimaging techniques, such as resting-state functional magnetic resonance imaging (rs-fMRI) have become useful tools in assessing HIV-associated abnormalities in the brain. The purpose of the current study was to examine the extent to which HIV infection in virologically suppressed patients is associated with disruptions in subcortical regions of the brain in comparison to a matched HIV-negative control group. The sample consisted of 72 patients and 39 controls included between January 2012 and January 2014. Resting state functional connectivity was determined between fourteen regions-of-interest (ROI): the left and right nucleus accumbens, amygdala, caudate nucleus, hippocampus, putamen, pallidum and thalamus. A Bayesian method was used to estimate resting-state functional connectivity, quantified in terms of partial correlations. Both groups showed the strongest partial correlations between the left and right caudate nucleus and the left and right thalamus. However, no differences between the HIV patients and controls were found between the posterior expected network densities (control network density = 0.26, SD = 0.05, patient network density = 0.26, SD = 0.04, p = 0.58). The results of the current study show that HIV does not affect subcortical connectivity in virologically controlled patients who are otherwise healthy.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/fisiopatología , Adulto , Anciano , Algoritmos , Teorema de Bayes , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Quimioterapia Combinada , Femenino , Infecciones por VIH/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Estudios Prospectivos , DescansoRESUMEN
The objectives of the current study were to examine cognitive decline in relation to psychological wellbeing, HIV disease and treatment characteristics and baseline variables over a one-year period of time in a group of HIV-infected patients on long term cART with undetectable viral load in comparison to a HIV-negative control group. Eighty-two of 95 patients and 43 of 55 controls who completed a baseline assessment for the Art-NeCo study underwent a follow-up neuropsychological assessment. A repeated-measure general linear model analysis was performed to compare the performance at follow-up in comparison to baseline between the patients and controls. Reliable change indices were computed as a measure of significant change in cognitive function. Compared to controls, patients overall performed worse on the domain speed of information processing. In the patient group a worse performance at follow-up was present for the verbal fluency domain compared to the controls, in the absence of a baseline group difference. For the executive function domain, no group differences were found at follow-up, but the patients performed worse than the controls at baseline. We found that cognitive decline was related to more frequent use of recreational drugs and a somewhat heightened level of irritability and more somatic complaints at baseline. However, the decliners did not differ from the non-decliners on any of the HIV-related variables.
Asunto(s)
Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Función Ejecutiva/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Adulto , Cognición , Disfunción Cognitiva , Femenino , Estudios de Seguimiento , Infecciones por VIH/virología , VIH-1 , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Calidad de Vida , Carga ViralAsunto(s)
Antivirales/efectos adversos , Interacciones Farmacológicas , Infecciones por VIH/complicaciones , Hepatitis C/tratamiento farmacológico , Prolina/análogos & derivados , Rilpivirina/efectos adversos , Adulto , Antivirales/farmacocinética , Humanos , Masculino , Países Bajos , Plasma/química , Prolina/efectos adversos , Prolina/farmacocinética , Rilpivirina/farmacocinéticaRESUMEN
BACKGROUND & AIMS: Acute hepatitis C virus infections (AHCV) are prevalent among HIV positive men having sex with men and generally treated with pegylated interferon-alpha (PegIFN) and ribavirin (RBV) during 24weeks. The addition of a protease inhibitor could shorten therapy without loss of efficacy. METHODS: We performed an open-label, single arm study to investigate the efficacy and safety of a 12-week course of boceprevir, PegIFN and RBV for AHCV genotype 1 infections in 10 Dutch HIV treatment centers. The primary endpoint of the study was achievement of sustained virological response rate at week 12 (SVR12) in patients reaching a rapid viral response at week 4 (RVR4) and SVR12 in the intent to treat (ITT) entire study population was the most relevant secondary endpoint. RESULTS: One hundred twenty-seven AHCV patients were screened in 16 months, of which 65 AHCV genotype 1 patients were included. After spontaneous clearance in six patients and withdrawal before treatment initiation in two, 57 started therapy within 26 weeks after infection. RVR4 rate was 72%. SVR12 rate was 100% in the RVR4 group. SVR12 rate in the ITT group was 86% and comparable to the SVR12 rate of 84% in 73 historical controls treated for 24 weeks with PegIFN and RBV in the same study centers. CONCLUSION: With the addition of boceprevir to PegIFN and RBV, treatment duration of AHCV genotype 1 can be reduced to 12 weeks without loss of efficacy. Given the high drug costs and limited availability of interferon-free regimens, boceprevir PegIFN and RBV can be a considered a valid treatment option for AHCV. ClinicalTrials.gov, number NCT01912495.
Asunto(s)
Antivirales/administración & dosificación , Hepatitis C/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Prolina/análogos & derivados , Ribavirina/administración & dosificación , Enfermedad Aguda , Adulto , Quimioterapia Combinada , Femenino , Hepatitis C/psicología , Hepatitis C/virología , Humanos , Interferón alfa-2 , Masculino , Persona de Mediana Edad , Prolina/administración & dosificación , Estudios Prospectivos , Calidad de Vida , Proteínas Recombinantes/administración & dosificaciónRESUMEN
OBJECTIVE: The objective of the current study is to integrate results from extensive neuropsychological assessment, subjective wellbeing reports and structural neuroimaging findings in successfully treated HIV-infected patients in comparison with a HIV-negative control group. DESIGN: A cross-sectional study. METHODS: Neuropsychological functioning and self-reported wellbeing were assessed in a group of 102 virologically suppressed HIV-infected patients on combination antiretroviral therapy (cART) and 56 controls. Both groups underwent magnetic resonance (MR) examinations and grey matter, white matter and subcortical volumes were determined. Brain parenchymal fraction (BPF) was calculated as an estimated measure of global brain atrophy. RESULTS: HIV-infected patients showed worse information processing speed (Pâ=â0.01) and motor function (Pâ=â0.03) than controls. Also, higher levels of anxiety and depressive symptoms, somatic and cognitive complaints, sleep problems and health distress were found, as well as lower levels of general health perceptions, social functioning and energy (Pâ<â0.05). No differences in wellbeing reports were found between patients on regimens containing either efavirenz or nevirapine and patients on cART without these drugs (Pâ>â0.05). Patients had a smaller BPF (Pâ=â0.04) and thalamus (Pâ=â0.05) than controls. A lower BPF was related to worse motor function and information processing speed in the patients. A smaller thalamus volume was related to lower motor function in the patient group and lower speed of information processing in the controls. CONCLUSION: No profound deficits were found in the current study. The present results demonstrate that HIV has a minor impact on brain, cognition and wellbeing among HIV-infected patients who are otherwise healthy and maintained on a good control of cART.
Asunto(s)
Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente Activa , Encéfalo/fisiología , Cognición , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Calidad de Vida/psicología , Adolescente , Adulto , Anciano , Encéfalo/patología , Estudios Transversales , Femenino , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Hepatitis C virus (HCV)/HIV-coinfected patients respond worse to dual therapy with ribavirin (RBV)/peginterferon compared with HCV-monoinfected patients. Several trials found that lower RBV plasma concentrations are associated with impaired virological response rates. The aim of this study was to determine RBV plasma concentrations in a cohort of HCV-monoinfected and HCV/HIV-coinfected patients. Our hypothesis is that HCV/HIV-coinfected patients have lower RBV plasma concentrations, which may in part explain their inferior response to dual therapy. METHODS: A retrospective cohort study was performed in chronic HCV-monoinfected and HCV/HIV-coinfected patients who received peginterferon and weight-based RBV. Plasma RBV concentrations were determined at weeks 4 and 12 by a validated high-performance liquid chromatography assay. RBV concentrations were compared between monoinfected and coinfected patients. We calculated the proportion of patients with a subtherapeutic RBV plasma concentration defined as <2.0 mg/L. RESULTS: A total of 61 HCV-infected patients were included, of whom 21 (34%) were coinfected with HIV. Although there was no difference in the weight-based dose of RBV between monoinfected and coinfected patients, RBV exposure was significantly lower in HCV/HIV-coinfected patients than in HCV-monoinfected patients: the mean ± SD RBV plasma concentrations were 1.82 ± 0.63 mg/L versus 2.25 ± 0.80 mg/L (P = 0.04) at week 4 and 2.14 ± 0.65 mg/L versus 2.62 ± 0.81 mg/L (P = 0.05) at week 12, respectively. The percentage of patients with subtherapeutic plasma concentrations of RBV in coinfected patients versus monoinfected patients was 62% versus 46% (P = 0.240) at week 4 and 50% versus 16% (P = 0.01) at week 12 of treatment, respectively. CONCLUSIONS: HIV/HCV-coinfected patients yield significantly lower plasma concentrations of RBV than HCV-monoinfected patients. This puts them at an increased risk of not achieving sustained virological response.
Asunto(s)
Antivirales/farmacocinética , Infecciones por VIH/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Ribavirina/farmacocinética , Adulto , Antivirales/administración & dosificación , Cromatografía Líquida de Alta Presión/métodos , Estudios de Cohortes , Coinfección , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Hepatitis C Crónica/virología , Humanos , Interferones/administración & dosificación , Masculino , Persona de Mediana Edad , Polietilenglicoles/química , Estudios Retrospectivos , Ribavirina/administración & dosificación , Factores de TiempoRESUMEN
In patients with syphilis, central nervous system (CNS) involvement is often difficult to determine. In patients who also are infected with human immunodeficiency virus (HIV), this is even more challenging, as cerebrospinal fluid (CSF) pleocytosis can be attributed to HIV, syphilis, or both. Hence, this study investigated (i) CSF chemokine (C-X-C motif) ligand 13 (CXCL13) as a potential marker to diagnose neurosyphilis in HIV-infected individuals and (ii) the added value of CSF CXCL13 to conventional CSF biomarkers, such as the rapid plasma reagin test (RPR), in diagnosing neurosyphilis. We included 103 syphilis patients from two centers in The Netherlands: 47 non-HIV-infected patients and 56 HIV-infected patients. A positive CSF-RPR was regarded as the gold standard for neurosyphilis. CSF CXCL13 levels were significantly higher in neurosyphilis patients when neurosyphilis was diagnosed by CSF-RPR (P = 0.0002) than in the syphilis control group. The sensitivity and specificity of CSF CXCL13 (cutoff of 76.3 pg/ml) to diagnose neurosyphilis by using positive CSF-RPR as the gold standard were 50% and 90%, respectively. CSF CXCL13 had an added value to CSF-RPR positivity in 70% of HIV-positive patients and in 33% of HIV-negative patients. Our data show that CSF CXCL13 might be a potential additional marker in neurosyphilis when other markers are not conclusive. The added value of CSF CXCL13 measurement to the current neurosyphilis gold standard appears to benefit HIV-positive patients more than HIV-negative patients.
Asunto(s)
Biomarcadores/líquido cefalorraquídeo , Quimiocina CXCL13/líquido cefalorraquídeo , Pruebas Diagnósticas de Rutina/métodos , Neurosífilis/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Infecciones por VIH/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Neurosyphilis is a tertiary form of syphilis and is caused by the spirochete Treponema pallidum. Today, more than one type of neurosyphilis often manifest simultaneously, which can pose difficulties to the diagnostic process. CASE DESCRIPTION: A 45-year-old man presented with an attack of stammering and loss of strength in the right half of his body. Diagnostic testing led to a suspected TIA and the man was treated as such. It was only a few months later, when he had developed more neurological symptoms, that the diagnosis of 'neurosyphilis' was made. Despite treatment with benzyl penicillin, he also developed symptoms of a psychiatric nature. CONCLUSION: The patient described in this article had symptoms consistent with both meningovascular syphilis and generalised paresis. Detailed history-taking was necessary to make the diagnosis (the patient had a history of gonorrhoea). A seemingly insignificant detail - an elevated estimated sedimentation rate - was an important clue.
Asunto(s)
Antibacterianos/uso terapéutico , Neurosífilis/diagnóstico , Penicilina G/uso terapéutico , Ceftriaxona/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Neurosífilis/complicaciones , Neurosífilis/tratamiento farmacológico , Paresia/diagnóstico , Paresia/etiología , Serodiagnóstico de la Sífilis , Treponema pallidum/aislamiento & purificaciónRESUMEN
A 55-year-old man presented with a painless destruction of multiple joints and neurologic deficits. He was admitted with a painless pyogenic arthritis of the right ankle. Four years earlier, he had experienced instability of the right knee after an inexplicable, progressive but painless destruction of the joint. Radiographs showed erosive changes at the smaller joints of both hands and the left foot, as well as deformation and destruction of the right foot. Results from both treponemal and nontreponemal serologic test were positive in blood. The Treponema pallidum particle agglutination index was positive in the cerebrospinal fluid. Tabetic arthropathy was diagnosed.Tabetic arthropathy is a manifestation of neurosyphilis. Because syphilis is known as "the great imitator" and tertiary syphilis is rare, recognizing the disease is the biggest challenge for health care providers. Symptoms may mimic any other disease, and many different medical specialists may be faced with these patients, or as Sir William Osler put it: "He who knows syphilis, knows medicine." Initial diagnosis is usually made on serum and cerebrospinal fluid examination. Penicillin is an effective treatment for neurosyphilis to stop progression of neurologic damage, but it does not cure the previously developed tabetic arthropathy. This case is reported to raise awareness of this uncommon but important manifestation of tertiary syphilis. Unfamiliarity with the clinical presentation of tabetic arthropathy may lead to considerable delay in diagnosis.
Asunto(s)
Artritis/diagnóstico por imagen , Artropatía Neurógena/diagnóstico por imagen , Deformidades Adquiridas de la Articulación/diagnóstico por imagen , Neurosífilis/complicaciones , Treponema pallidum/patogenicidad , Artritis/patología , Artritis/terapia , Artropatía Neurógena/patología , Artropatía Neurógena/terapia , Diagnóstico Diferencial , Humanos , Deformidades Adquiridas de la Articulación/patología , Deformidades Adquiridas de la Articulación/terapia , Masculino , Persona de Mediana Edad , Neurosífilis/diagnóstico por imagen , Neurosífilis/patología , Neurosífilis/terapia , Penicilinas/uso terapéutico , Radiografía , Tabes Dorsal/complicaciones , Resultado del TratamientoRESUMEN
Resistance mutations to the HIV-1 fusion inhibitor enfuvirtide emerge mainly within the drug's target region, HR1, and compensatory mutations have been described within HR2. The surrounding envelope (env) genetic context might also contribute to resistance, although to what extent and through which determinants remains elusive. To quantify the direct role of the env context in resistance to enfuvirtide and in viral infectivity, we compared enfuvirtide susceptibility and infectivity of recombinant viral pairs harboring the HR1-HR2 region or the full Env ectodomain of longitudinal env clones from 5 heavily treated patients failing enfuvirtide therapy. Prior to enfuvirtide treatment onset, no env carried known resistance mutations and full Env viruses were on average less susceptible than HR1-HR2 recombinants. All escape clones carried at least one of G36D, V38A, N42D and/or N43D/S in HR1, and accordingly, resistance increased 11- to 2800-fold relative to baseline. Resistance of full Env recombinant viruses was similar to resistance of their HR1-HR2 counterpart, indicating that HR1 and HR2 are the main contributors to resistance. Strictly X4 viruses were more resistant than strictly R5 viruses, while dual-tropic Envs featured similar resistance levels irrespective of the coreceptor expressed by the cell line used. Full Env recombinants from all patients gained infectivity under prolonged drug pressure; for HR1-HR2 viruses, infectivity remained steady for 3/5 patients, while for 2/5 patients, gains in infectivity paralleled those of the corresponding full Env recombinants, indicating that the env genetic context accounts mainly for infectivity adjustments. Phylogenetic analyses revealed that quasispecies selection is a step-wise process where selection of enfuvirtide resistance is a dominant factor early during therapy, while increased infectivity is the prominent driver under prolonged therapy.
Asunto(s)
Farmacorresistencia Viral/genética , Proteína gp41 de Envoltorio del VIH/farmacología , Inhibidores de Fusión de VIH/farmacología , VIH-1/genética , Fragmentos de Péptidos/farmacología , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Secuencia de Bases , Farmacorresistencia Viral/efectos de los fármacos , Enfuvirtida , Genotipo , Células HEK293 , VIH-1/efectos de los fármacos , VIH-1/patogenicidad , Humanos , Concentración 50 Inhibidora , Fenotipo , Filogenia , Estructura Secundaria de Proteína , Recombinación Genética/genética , Tropismo/efectos de los fármacos , Tropismo/genética , ViriónRESUMEN
The authors describe an HIV-infected patient with moderate renal failure receiving combination antiretroviral therapy. Because of dyslipidaemia he was initially treated with pravastatin but developed rhabdomyolysis after a switch to rosuvastatin. With this case we illustrate that statins as well as antiretroviral therapy are susceptible to clinical relevant drug-drug or drug-disease interactions. Knowledge of these interactions is important to provide patients with the best possible care.
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Fármacos Anti-VIH/efectos adversos , Fluorobencenos/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Pirimidinas/efectos adversos , Pirimidinonas/efectos adversos , Insuficiencia Renal/complicaciones , Rabdomiólisis/tratamiento farmacológico , Ritonavir/efectos adversos , Sulfonamidas/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Quimioterapia Combinada , Dislipidemias/inducido químicamente , Dislipidemias/tratamiento farmacológico , Fluorobencenos/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Lopinavir , Masculino , Persona de Mediana Edad , Pirimidinas/uso terapéutico , Pirimidinonas/uso terapéutico , Insuficiencia Renal/tratamiento farmacológico , Rabdomiólisis/inducido químicamente , Ritonavir/uso terapéutico , Rosuvastatina Cálcica , Sulfonamidas/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVES: HIV-associated neurocognitive disorders remain common despite use of potent antiretroviral therapy (ART). Ongoing viral replication due to poor distribution of antivirals into the CNS may increase risk for HIV-associated neurocognitive disorders. This study's objective was to determine penetration of a commonly prescribed antiretroviral drug, efavirenz, into CSF. METHODS: CHARTER is an ongoing, North American, multicentre, observational study to determine the effects of ART on HIV-associated neurological disease. Single random plasma and CSF samples were drawn within 1 h of each other from subjects taking efavirenz between September 2003 and July 2007. Samples were assayed by HPLC or HPLC/mass spectrometry with detection limits of 39 ng/mL (plasma) and <0.1 ng/mL (CSF). RESULTS: Eighty participants (age 44 ± 8 years; 79 ± 15 kg; 20 females) had samples drawn 12.5 ± 5.4 h post-dose. The median efavirenz concentrations after a median of 7 months [interquartile range (IQR) 2-17] of therapy were 2145 ng/mL in plasma (IQR 1384-4423) and 13.9 ng/mL in CSF (IQR 4.1-21.2). The CSF/plasma concentration ratio from paired samples drawn within 1 h of each other was 0.005 (IQR 0.0026-0.0076; n = 69). The CSF/IC(50) ratio was 26 (IQR 8-41) using the published IC(50) for wild-type HIV (0.51 ng/mL). Two CSF samples had concentrations below the efavirenz IC(50) for wild-type HIV. CONCLUSIONS: Efavirenz concentrations in the CSF are only 0.5% of plasma concentrations but exceed the wild-type IC(50) in nearly all individuals. Since CSF drug concentrations reflect those in brain interstitial fluids, efavirenz reaches therapeutic concentrations in brain tissue.
Asunto(s)
Fármacos Anti-VIH/líquido cefalorraquídeo , Benzoxazinas/líquido cefalorraquídeo , Infecciones por VIH/líquido cefalorraquídeo , Infecciones por VIH/tratamiento farmacológico , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Adulto , Alquinos , Fármacos Anti-VIH/sangre , Fármacos Anti-VIH/uso terapéutico , Benzoxazinas/sangre , Benzoxazinas/uso terapéutico , Encéfalo , Cromatografía Líquida de Alta Presión , Ciclopropanos , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Humanos , Concentración 50 Inhibidora , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/virología , Distribución Aleatoria , Carga ViralRESUMEN
BACKGROUND: Ribavirin is an essential component in the treatment of chronic hepatitis C (HCV) infection. Although ribavirin dose is weight-based, data in the literature suggest large between-patient variability in plasma ribavirin concentrations. Recent studies indicate that higher ribavirin exposure results in higher sustained viral response rates. Monitoring ribavirin concentration is suggested in the literature, but it is unclear at what time point during treatment plasma ribavirin concentrations should be monitored. AIM: To investigate the association between early plasma ribavirin concentrations and ribavirin dosing with steady-state (Css) concentration and the between- and within-patient variability in plasma ribavirin concentration in clinical practice. METHODS: We performed a prospective observational cohort study in patients with HCV who received pegylated interferon in combination with oral weight-based ribavirin (12-15 mg/kg) twice daily. Trough plasma ribavirin concentrations at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 were studied using a validated high-performance liquid chromatography assay. RESULTS: In total, 53 patients (37 male, 16 female) with a mean age of 51 years (range, 26-68 years) were included and 209 samples were collected. There was a significant correlation between Week 2 as well as Week 4 and plasma ribavirin Css (r = 0.589 and r = 0.714, P < 0.05, respectively). Ribavirin Css was reached at Week 8 of HCV treatment. There was no correlation between dose in mg/kg and Css (r = 0.181, P = 0.263). The between- and within-patient coefficients of variation of plasma ribavirin concentrations at Week 8 and beyond were 43% and 13%, respectively. CONCLUSION: In HCV-infected patients, ribavirin steady-state concentrations can be predicted by measurement of concentrations made early after the start of therapy.
Asunto(s)
Antivirales/sangre , Monitoreo de Drogas , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Ribavirina/sangre , Adulto , Anciano , Antivirales/efectos adversos , Antivirales/farmacocinética , Antivirales/uso terapéutico , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/sangre , Hepatitis C/complicaciones , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Recombinantes , Ribavirina/efectos adversos , Ribavirina/farmacocinética , Ribavirina/uso terapéuticoAsunto(s)
Adenina/análogos & derivados , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/farmacocinética , Benzoxazinas/administración & dosificación , Benzoxazinas/farmacocinética , Desoxicitidina/análogos & derivados , Organofosfonatos/administración & dosificación , Organofosfonatos/farmacocinética , Oxazinas/administración & dosificación , Oxazinas/farmacocinética , Plasma/química , Adenina/administración & dosificación , Adenina/farmacocinética , Alquinos , Ciclopropanos , Desoxicitidina/administración & dosificación , Desoxicitidina/farmacocinética , Combinación de Medicamentos , Combinación Efavirenz, Emtricitabina y Fumarato de Tenofovir Disoproxil , Infecciones por VIH/tratamiento farmacológico , HumanosRESUMEN
Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested. We performed a randomized, open-label, multicenter, 96-week comparative study in antiretroviral therapy (ART)-naïve patients with CD4
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Fármacos Anti-VIH/uso terapéutico , Didesoxinucleósidos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Lamivudine/uso terapéutico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Zidovudina/uso terapéutico , Adulto , Anciano , Recuento de Linfocito CD4 , Quimioterapia Combinada , Femenino , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Lamivudine/administración & dosificación , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Resultado del Tratamiento , Carga Viral , Adulto Joven , Zidovudina/administración & dosificaciónRESUMEN
Three patients, two women aged 54 and 84 years, and a man aged 76 years, had serious complications during a stay in an internal medicine ward. The complications were discussed at monthly multidisciplinary complication meetings, which we organise from 2007 and which are aimed at improving care processes. The first patient developed urinary tract infection, fever and delirium and an arm fracture as a result of a fall after she had been given a routine urinary catheter in order to monitor her fluid balance. The complication discussion indicated that a urinary catheter should not be routinely installed. The second patient developed phlebitis and endocarditis after a venous infusion had been present for several days. As a result of the complication discussion it was decided that venous access was to be renewed after 96 h. The third patient, who was treated for atrial fibrillation, had fatal intracerebral bleeding due to INR > 5. A result of the complication discussion was that active antagonism of anticoagulants is warranted in these cases, not just discontinuation of the anticoagulants. The monthly multidisciplinary complication discussions in our department have led to a change in culture, facilitating the expression of doubts and criticisms, and a readiness to change policies.
Asunto(s)
Hospitalización , Medicina Interna/normas , Atención al Paciente/normas , Calidad de la Atención de Salud , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Vitamin D regulates bone metabolism but has also immunoregulatory properties. In HIV-infected patients bone disorders are increasingly observed. Furthermore, low 1,25(OH)(2)D(3) levels have been associated with low CD4(+) counts, immunological hyperactivity, and AIDS progression rates. Few studies have examined the vitamin D status in HIV-infected patients. This study will specifically focus on the effects of antiretroviral agents on vitamin D status. Furthermore, the effect of vitamin D status on CD4 cell recovery after initiation of HAART will be evaluated. Among 252 included patients the prevalence of vitamin D deficiency (<35 nmol/liter from April to September and <25 nmol/liter from October to March) was 29%. Female sex, younger age, dark skin, and NNRTI treatment were significant risk factors in univariate analysis, although in multivariate analyses skin pigmentation remained the only independent risk factor. Median 25(OH)D(3) levels were significantly lower in white NNRTI-treated patients [54.5(27.9-73.8) nmol/liter] compared to white PI-treated patients [77.3 (46.6-100.0) nmol/liter, p = 0.007], while among nonwhites no difference was observed. Both PI- and NNRTI-treated patients had significantly higher blood PTH levels than patients without treatment. Moreover, NNRTI treatment puts patients at risk of elevated PTH levels (>6.5 pmol/liter). Linear regression analysis showed that vitamin D status did not affect CD4 cell recovery after initiation of HAART. In conclusion, 29% of the HIV-1-infected patients had vitamin D deficiency, with skin color as an independent risk factor. NNRTI treatment may add more risk for vitamin D deficiency. Both PI- and NNRTI-treated patients showed higher PTH levels and might therefore be at risk of bone problems. Evaluation of 25(OH)D(3) and PTH levels, especially in NNRTI-treated and dark skinned HIV-1-infected patients, is necessary to detect and treat vitamin D deficiency early.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , VIH-1/aislamiento & purificación , Deficiencia de Vitamina D/inducido químicamente , Adulto , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/inmunología , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Hormona Paratiroidea/sangre , Prevalencia , Factores de Riesgo , Pigmentación de la PielAsunto(s)
Diarrea/inducido químicamente , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/efectos adversos , VIH-1 , Interacciones de Hierba-Droga , Pirimidinonas/efectos adversos , Humanos , Lopinavir , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Previous research in healthy volunteers has demonstrated that rifampicin and adjusted doses of lopinavir/ritonavir soft-gel capsules resulted in adequate exposure to lopinavir. Our objective was to study the combined use of rifampicin and the newly introduced lopinavir/ritonavir tablets. METHODS: A total of 40 healthy volunteers were planned to start with 600 mg rifampicin once daily from days 1-5. From days 6-15, volunteers were randomized to receive lopinavir/ritonavir tablets dosed as either 600/150 or 800/200 mg twice daily, both in addition to 600 mg rifampicin once daily. A 12 h pharmacokinetic curve was planned on day 15. Safety assessments were conducted regularly throughout the study period. RESULTS: Eleven volunteers started as the first group in this study. No major complaints occurred during day 1-5 (rifampicin only). After addition of lopinavir/ritonavir, eight volunteers suffered from both nausea and vomiting, one from nausea only, and one from vomiting only. On day 7, increases in aspartate aminotransferase/alanine aminotransferase (AST/ALT) levels were reported in all volunteers and on day 8, the study was prematurely terminated. The AST/ALT levels continued to rise and peaked (grade 2, n = 2; grade 3, n = 1; grade 4, n = 8) on days 9-10. All values returned to normal within 6 weeks. CONCLUSIONS: The study showed a high incidence of adverse events when a higher than standard dose of the new lopinavir/ritonavir tablets was combined with rifampicin. In the future, this drug combination should not be given to healthy volunteers. Liver function should be carefully monitored when rifampicin and lopinavir/ritonavir are combined in patients.
Asunto(s)
Antibióticos Antituberculosos/efectos adversos , Inhibidores de la Proteasa del VIH/efectos adversos , Pirimidinonas/efectos adversos , Rifampin/efectos adversos , Ritonavir/efectos adversos , Adulto , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Esquema de Medicación , Combinación de Medicamentos , Interacciones Farmacológicas , Femenino , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/sangre , Humanos , Lopinavir , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Pirimidinonas/administración & dosificación , Pirimidinonas/sangre , Rifampin/administración & dosificación , Rifampin/sangre , Ritonavir/administración & dosificación , Ritonavir/sangre , Comprimidos , Vómitos/inducido químicamenteRESUMEN
HIV-infected patients in sub-Saharan countries highly depend on traditional medicines for the treatment of opportunistic oral infections as candidiasis. Previous investigations on antifungal activity of medicinal plant extracts utilized by traditional healers in Tanzania have revealed 12 extracts with potent antifungal activity. Although the plants may be good candidates for new treatment opportunities, they can be toxic or genotoxic and could cause pharmacokinetic interactions when used concomitantly with antiretroviral agents. Therefore, we investigated the cytotoxicity, genotoxicity and cytochrome P450 interaction potential of these medicinal plants. Cytotoxicity was tested by Hoechst 33342, Alamar Blue, calcein-AM, glutathione depletion and O(2)-consumption assays and genotoxicity by a Vitotox assay. Competition of the 12 extracts on substrate metabolism by CYP3A4, 2C9, 2C19 and 2D6 was tested with high-throughput CYP inhibition screening. Pregnane X receptor (PXR) activation was tested using Chinese hamster ovary cell lines expressing human PXR. Herbal extracts inducing high human PXR activation were tested for enhanced CYP3A4 mRNA levels with quantitative polymerase chain reaction. Genotoxicity was found for Jatropha multifida, Sterculia africana and Spirostachys africana. All plant extracts showed high cytotoxic effects in almost all tests. Potent competition with CYP3A4, 2D6, 2C9 and 2C19 was found for 75% of the herbal extracts. Spirostachys africana did not affect CYP2D6 and for S. africana and Turraea holstii no effect on CYP2D6 and CYP3A4 (DBF) was found. Nine plant extracts showed significant activation of human PXR, but only Agaura salicifolia, Turraea holstii and S. africana significantly induced CYP3A4 mRNA levels. These results indicate the possibility of potential medicinal plant-antiretroviral interactions.