RESUMEN
BACKGROUND: The effects of ezetimibe on cholesterol metabolism in HIV-infected patients receiving boosted protease inhibitors have not been thoroughly assessed. The aim of this study was to assess cholesterol homeostasis in patients with PI associated dyslipidemia and its relationship with the response to treatment with the cholesterol-absorption inhibitor ezetimibe. METHODS: Fifteen patients with ritonavir-boosted PI-containig therapy and LDL-cholesterol > 3.36 mmol/L (>130 mg/dL) were assessed at baseline and after an 8-week course of ezetimibe 10 mg/d. Serum non-cholesterol sterols were measured at each visit as markers of cholesterol synthesis and absorption. Total-, LDL-, and HDL-cholesterol triglycerides, apolipoproteins A1 and B, high sensitivity C-reactive protein, CD4 cells and HIV-1 RNA were also measured. RESULTS: Ezetimibe treatment was well tolerated in all patients and resulted in significant reductions in total cholesterol (-11.4%, p = .002), LDL-cholesterol (-20.4%, p = .003), non-HDL-cholesterol (-13.4%, p = .002) and apolipoprotein B (-9.1%, p = .021). Treatment with ezetimibe was associated with decreased cholesterol absorption markers (campesterol-to-cholesterol ratio -43.0%, p = .001; sitosterol-to-cholesterol ratio -41.9%, p = .001) and increased synthesis markers (lathosterol-to-cholesterol ratio 53.2%, p = .005). Baseline absorption or synthesis markers were unrelated to the response to treatment. CD4 cell count and plasma HIV-1 RNA remained unchanged. CONCLUSIONS: The level of cholesterol absorption or synthesis does not appear to be a major determinant of the responsiveness to ezetimibe in patients on ritonavir-boosted PI-containing therapy. TRIAL REGISTRATION: EudraCT: 2006-006156-36.
Asunto(s)
Azetidinas/uso terapéutico , LDL-Colesterol/metabolismo , Dislipidemias/tratamiento farmacológico , Infecciones por VIH/complicaciones , Inhibidores de Proteasas/uso terapéutico , Adulto , Anciano , Anticolesterolemiantes/uso terapéutico , Proteína C-Reactiva/química , Colesterol/análogos & derivados , Colesterol/uso terapéutico , Ezetimiba , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Metabolismo de los Lípidos , Masculino , Persona de Mediana Edad , Fitosteroles/uso terapéutico , Inhibidores de Proteasas/efectos adversosRESUMEN
BACKGROUND: Renal function and albuminuria predict cardiovascular disease (CVD) in general population. However, their prognostic value in patients with resistant hypertension (RH) is somewhat unknown. OBJECTIVE: To determine the ability of renal function and albuminuria to predict CVD in RH patients. METHODS: One hundred and thirty-three RH (blood pressure [BP] ≥140/90mmHg despite treatment with ≥3 drugs) patients were evaluated. Median follow-up was 73 months. Primary endpoint was a composite of non-fatal cardiovascular events or cardiovascular death. Serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) were determined. Microalbuminuria was defined as a urinary albumin-to-creatinine ratio (UACR) ≥30mg/g. RESULTS: Twenty-two patients (16.5%) reached the primary endpoint. Long-term elevated UACR (66 vs. 17mg/g, P=0.045), but not at baseline, was associated with the primary endpoint, after adjusting for age, prior CVD, and both eGFR and office systolic-BP at baseline and during follow-up. Although baseline SCr and eGFR were associated with CVD, significance was lost after baseline risk adjustment. Baseline microalbuminuria prevalence was 45% and 41% in patients with and without CVD (P=0.813), while percentages of patients with microalbuminuria at follow-up were 67% and 28%, respectively (P=0.002). More patients with de novo CVD, compared with those without CVD, developed microalbuminuria at follow-up (28% vs. 6%) or had persistent microalbuminuria (39% vs. 21%), while fewer patients with CVD had microalbuminuria regression (11% vs. 19%) or remained normoalbuminurics (22% vs. 53%; overall P=0.005). CONCLUSION: In RH patients, the inability to microalbuminuria regression, either due to persistence or new appearance, independently predicts CVD.
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Albuminuria/orina , Enfermedades Cardiovasculares/etiología , Hipertensión/complicaciones , Anciano , Albuminuria/complicaciones , Albuminuria/fisiopatología , Enfermedades Cardiovasculares/epidemiología , Creatinina/sangre , Resistencia a Medicamentos , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , España/epidemiologíaRESUMEN
BACKGROUND: The aim of this study was to assess the short-term and long-term consequences of stopping antiretroviral therapy (ART) in patients with preserved immune function. METHODS: This was a randomized 144-week follow-up CD4⺠T-cell-count-guided treatment-interruption trial. HIV-1-infected adults with plasma HIV-1 RNA<50 copies/ml, CD4⺠T-cell count >500 cells/µl and nadir CD4⺠T-cell count >100 cells/µl were randomized to continuous treatment (CT) or treatment interruption (TI) until CD4⺠T-cell count decreased to <350 cells/µl. The primary end points were AIDS-defining illnesses, death, CD4⺠T-cell count <200 cells/µl, or virological failure after restarting ART. RESULTS: A total of 106 patients were included, 50 in the CT arm and 56 in the TI arm. A trend to a higher rate of primary end points was observed in the TI group (26.8% versus 14%, difference 12.8%, 95% CI -2.3, 27.8; P=0.105). In addition, 10 patients presented clinical events related with HIV rebound, including 8 cases of thrombocytopaenia. The CD4⺠T-cell count significantly decreased in the TI group (even in patients with persistently high CD4⺠T-cell counts and no clinical events) versus the CT group (median change -408 cells/µl versus -21.5 cells/µl; P<0.001), whereas a significant increase in CD8⺠T-cell count was observed (256 cells/µl versus -59 cells/µl; P<0.001). The time to ART re-initiation was significantly associated with nadir and baseline CD4⺠T-cell counts. CONCLUSIONS: Discontinuation of ART in patients with preserved immune function is followed by significant immunological impairment even in those with no clinical events, and may be associated with an increased risk of HIV-related complications. Hence, patients who stop ART voluntarily should be closely monitored, regardless of their CD4⺠T-cell count.
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Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Progresión de la Enfermedad , Esquema de Medicación , Quimioterapia Combinada , Femenino , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/administración & dosificación , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Inhibidores de la Transcriptasa Inversa/uso terapéutico , España , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
Recent reports have suggested an increased risk of acute hepatitis C (AHC) infection in homosexual HIV-infected men and that early treatment with interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution. A retrospective analysis of 38 HIV-infected patients who were consecutively diagnosed as developing AHC, defined by both seroconversion of anti-hepatitis C virus (HCV) antibodies and detection of serum HCV-RNA in those with previous negative results. Thirty-six patients were men with history of unprotected sexual intercourse with men and two were women with sexual and nosocomial risk factors. AHC infection was asymptomatic in 26 patients; asthenia and jaundice were the most frequent symptoms. HCV genotype 1 was present in 19 patients and genotype 4 in 14 patients. Thirty-five patients received early antiviral treatment with pegylated interferon-alfa associated with ribavirin; 15 of the 32 patients who completed the follow-up (47%) achieved a sustained virological response, as defined by undetectable HCV-RNA 6 months after the end of therapy. There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men. In our experience, early treatment of AHC with pegylated interferon-alfa plus ribavirin in HIV patients achieves poor results.
Asunto(s)
Antivirales/farmacología , Seropositividad para VIH/inmunología , Anticuerpos contra la Hepatitis C/inmunología , Hepatitis C/inmunología , Interferón-alfa/farmacología , Ribavirina/farmacología , Enfermedad Aguda , Adulto , Antivirales/administración & dosificación , Brotes de Enfermedades , Femenino , Estudios de Seguimiento , Genotipo , Seropositividad para VIH/tratamiento farmacológico , Seropositividad para VIH/epidemiología , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , Filogenia , Estudios Retrospectivos , Ribavirina/administración & dosificación , Factores de Riesgo , España/epidemiologíaRESUMEN
BACKGROUND: Structured antiretroviral therapy interruption (TI) is discouraged because of poorer AIDS and non-AIDS-related outcomes, but is often inevitable in clinical practice. Certain strategies could reduce the emergence of resistance mutations related to TI. METHODS: A total of 106 HIV-1-infected patients on stable HAART with undetectable plasma viral load were randomized to therapy continuation (n=50) or CD4(+) T-cell-guided TI (n=56). Staggered interruption involved stopping non-nucleoside reverse transcriptase inhibitors (NNRTIs) 7 days before the nucleoside backbone. Genotypic resistance testing (GRT) was performed on proviral DNA from peripheral blood mononuclear cells (PBMCs) at baseline and before each TI, and on plasma RNA after each TI. RESULTS: At baseline, GRT on PBMCs detected mutations in nine patients and only two major mutations were identified. GRT on plasma samples performed after TIs showed nucleoside reverse transcriptase inhibitors (NRTI), NNRTI and protease inhibitor major resistance associated mutations in 10/56, 3/46 and 1/8 patients receiving these drugs, respectively. Only in two patients had the same mutations been observed in GRT on PBMCs at baseline. Three patients presented virological failure after resumption of therapy, all receiving NNRTIs. In one of them, resistance mutations detected at failure had been also observed previously in GRT on plasma after TI. CONCLUSIONS: Staggered interruption of NNRTIs 7 days before the nucleoside backbone does not avoid resistance emergence completely, but does not necessarily lead to virological failure after treatment resumption. Plasma HIV-1 RNA genotype after the interruption and the patient's treatment history seem to be more useful than baseline proviral DNA genotype to assess the risk of virological failure after restarting therapy.
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Fármacos Anti-VIH/administración & dosificación , Farmacorresistencia Viral/genética , Evolución Molecular , VIH-1/efectos de los fármacos , Leucocitos Mononucleares/virología , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , ADN Viral/sangre , ADN Viral/genética , Esquema de Medicación , Femenino , Genotipo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/genética , Humanos , Masculino , Provirus/genética , ARN Viral/sangre , ARN Viral/genética , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Resultado del TratamientoRESUMEN
We aimed to evaluate markers of vascular dysfunction in patients with resistant hypertension (RH). A group of 144 patients (61 years, 42% women) with essential RH were divided in two groups based on ambulatory blood pressure monitoring (ABPM). True RH (72%) was considered when 24-h blood pressure (BP) was ≥ 130 and/or 80 mmHg. Otherwise, patients were classified as white coat RH (28%). Hyperemia-induced forearm vasodilation (HIFV), serum inflammatory biomarkers (hs-CRP, s-ICAM-1, s-VCAM-1, e-selectin, p-selectin and MCP-1) and large (C1) and small arterial (C2) compliance (HDI/Pulse Wave CR 2000) were determined in all individuals. In comparison with patients with white coat RH, and after adjustment for age, office systolic BP and diabetes status, those with true RH had a more impaired HIFV (201 ± 159 vs 436 ± 157%; p < 0.001), increased e-selectin (53.1 ± 29.8 vs 40.7 ± 23.5 ng/ml; p = 0.035), and MCP-1 (445 ± 120 vs 386 ± 126 ng/ml; p = 0.027). No significant differences were observed in arterial compliance. Maximal HIFV inversely correlated with urinary albumin excretion (Rho: - 0.278; p = 0.004) and with some inflammatory biomarkers (MCP-1: - 0.441; p < 0.001, e-selectin: - 0.468; p < 0.001 and p-selectin: - 0.329; p = 0.001). We conclude that true RH, diagnosed by ABPM, is associated with a more severe degree of vascular dysfunction, as measured by HIFV and serum biomarkers, whereas other types of vascular alterations, such as compliance, are not directly linked with the level of BP.
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Vasos Sanguíneos/fisiopatología , Hipertensión/fisiopatología , Adulto , Anciano , Monitoreo Ambulatorio de la Presión Arterial , Adaptabilidad , Femenino , Antebrazo/irrigación sanguínea , Humanos , Masculino , Persona de Mediana Edad , VasodilataciónRESUMEN
OBJECTIVE: To compare 48-week changes in body fat distribution and bone mineral density (BMD) between patients switching from a ritonavir-boosted protease inhibitor (PI/r) to raltegravir (RAL) and patients continuing with PI/r. DESIGN: Substudy of the prospective, randomized, open-label, multicenter SPIRAL study. METHODS: Patients were randomized (1 : 1) to continue with the PI/r-based regimen or switch to RAL, maintaining the rest of the treatment unchanged. Dual-energy X-ray absorptiometry and computed tomography scans were performed at baseline and after 48 weeks to measure body fat and bone composition, analyzing intragroup and intergroup differences. RESULTS: Eighty-six patients were included and 74 patients (39 RAL, 35 PI/r) completed the substudy. Significant increases in median [interquartile range (IQR)] visceral adipose tissue (VAT) [20.7 (-2.4 to 45.6) cm(2), P = 0.002] and total adipose tissue (TAT) [21.4 (-1.3 to 55.4) cm(2), P = 0.013] were seen within the PI/r group. No significant changes in body fat were seen with RAL or between treatment groups. Regarding bone composition, total BMD [0.01 (0 to 0.02) g/cm(2), P = 0.002], total hip BMD [0.01 (0 to 0.03) g/cm(2), P = 0.015] and total hip T score [0.12 (-0.05 to 0.21) SD, P = 0.004] significantly increased with RAL, with no significant changes within the PI/r group. Differences between treatment groups were significant in femoral neck BMD [0.01 (-0.02 to 0.02) g/cm(2), P = 0.032] and T score [0.01 (-0.18 to 0.18) SD, P = 0.016]. CONCLUSION: Although there were no significant changes in body fat between groups, maintaining a PI/r-based regimen was associated with a significant increase in VAT and TAT. Switching to RAL led to a significant increase in femoral neck BMD when comparing between groups.
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Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Tejido Adiposo/diagnóstico por imagen , Fármacos Anti-VIH/farmacología , Composición Corporal/efectos de los fármacos , Densidad Ósea , Cuello Femoral/diagnóstico por imagen , Inhibidores de la Proteasa del VIH/efectos adversos , Pirrolidinonas/farmacología , Absorciometría de Fotón , Tejido Adiposo/efectos de los fármacos , Adulto , Fármacos Anti-VIH/uso terapéutico , Distribución de la Grasa Corporal , Densidad Ósea/efectos de los fármacos , Femenino , Cuello Femoral/efectos de los fármacos , Inhibidores de la Proteasa del VIH/administración & dosificación , Humanos , Lopinavir/efectos adversos , Lopinavir/farmacología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Pirrolidinonas/uso terapéutico , Raltegravir Potásico , Ritonavir/efectos adversos , Ritonavir/farmacocinética , Ritonavir/farmacología , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Antiretroviral therapy during pregnancy is critical to preventing human immunodeficiency virus vertical transmission. Physiological changes during pregnancy can alter drug kinetics. The aim of this study was to assess the pharmacokinetics (PK) of saquinavir (SQV) boosted with ritonavir during pregnancy and postpartum. Fourteen human immunodeficiency virus-positive pregnant women started SQV 500 mg new tablet formulation plus ritonavir at a dose of 1000/100 mg twice a day + 2 nucleoside retrotranscriptase inhibitors during pregnancy. At weeks 24 and 34 of pregnancy and 6 weeks postpartum, a 12-hour PK study was conducted. PK parameters were calculated using Win Nolin software version 4.1. At week 24, the geometric mean values for SQV area under the plasma concentration-time curve from 0-12 hours (AUC0â12), the maximum observed plasma concentration (C(max)), trough plasma concentration (C(min)), and the elimination half-life (t(1/2)) were 24.80 mg·h⻹·mL⻹, 4.66 mg/mL, 0.93 mg/mL, and 4.31 hours, respectively. At week 34, AUC0â12, C(max), C(min), and t(1/2) were 12.71 mg·h⻹·mL⻹, 3.23 mg/mL, 0.26 mg/mL, and 4.06 hours, respectively. Finally, at 6 weeks postpartum, mean values for SQV AUC0â12, C(max), C(min), and t(1/2) were 28.94 mg·h⻹·mL⻹, 3.92 mg/mL, 0.86 mg/mL, and 3.60 hours, respectively. Although PK parameters in week 24 and postpartum were very similar, those for week 34 showed an important reduction: -71.20%, -30.61%, -48.73%, and -5.81% in C(min), C(max), AUC0â12, and t(1/2), respectively, compared with week 24, but no statistically significant differences were shown between patients. No vertical transmissions were reported. Therapeutic drug monitoring of SQV during pregnancy should be considered, mainly during the third trimester, to ensure adequate drug exposure throughout the entire pregnancy.
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Inhibidores de la Proteasa del VIH/farmacocinética , Seropositividad para VIH/sangre , Seropositividad para VIH/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/sangre , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Ritonavir/farmacocinética , Saquinavir/farmacocinética , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/sangre , Inhibidores de la Proteasa del VIH/uso terapéutico , Seropositividad para VIH/complicaciones , Seropositividad para VIH/metabolismo , Semivida , Humanos , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Sobrepeso/complicaciones , Proyectos Piloto , Periodo Posparto , Embarazo , Complicaciones Infecciosas del Embarazo/metabolismo , Segundo Trimestre del Embarazo , Tercer Trimestre del Embarazo , Estudios Prospectivos , Ritonavir/efectos adversos , Ritonavir/sangre , Ritonavir/uso terapéutico , Saquinavir/efectos adversos , Saquinavir/sangre , Saquinavir/uso terapéuticoRESUMEN
La hepatitis aguda C (HAC) representa un problema sanitario en auge. A pesar del descenso de la transmisión del VHC por vía hematológica gracias a los programas de detección de donantes y el menor consumo de drogas por vía intravenosa, actualmente existe un aumento de su incidencia debido al contagio por vía sexual, sobretodo en pacientes homosexuales infectados por el VIH. La presentación de forma paucisintomática es frecuente, lo cual dificulta su diagnóstico. La eliminación espontánea del virus ocurre en el 25% de los casos y, habitualmente, durante los primeros tres meses tras el inicio de la clínica y en pacientes sintomáticos. Si el ARN del VHC persiste detectable pasado este tiempo debe iniciarse sin demora tratamiento antiviral, ya que en la fase aguda el porcentaje de respuesta viral sostenida es mayor al que se obtiene después en la hepatopatía crónica. La pauta de tratamiento óptima (interferón sólo o asociado a ribavirina), así como la duración de la misma no están claramente establecidas en el momento actual (AU)
Acute hepatitis C (AHC) is an increasing health issue. Despite the decline of blood-to-blood transmissionof hepatitis C virus (HCV) through donor screening programs and a decline in intravenous drug use, theincidence of sexual transmission has now increased, particularly in HIV-infected homosexual patients.The presentation is almost always asymptomatic, which complicates diagnosis. Spontaneous clearanceof the virus occurs in 25% of cases and usually, within the first three months after onset of symptomsand in symptomatic patients. If serum HCV-RNA remains detectable after this period, antiviral treatmentshould be started without delay, since sustained viral response rate in the acute phase is higher than thatachieved with chronic liver disease. The optimal treatment regimen (interferon alone or combined withribavirin) and its duration are not clearly established at the present time (AU)
Asunto(s)
Humanos , Masculino , Femenino , Hepatitis C/epidemiología , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Factores de Riesgo , España/epidemiologíaRESUMEN
BACKGROUND: Antiretroviral therapy has changed the natural history of human immunodeficiency virus (HIV) infection in developed countries, where it has become a chronic disease. This clinical scenario requires a new approach to simplify follow-up appointments and facilitate access to healthcare professionals. METHODOLOGY: We developed a new internet-based home care model covering the entire management of chronic HIV-infected patients. This was called Virtual Hospital. We report the results of a prospective randomised study performed over two years, comparing standard care received by HIV-infected patients with Virtual Hospital care. HIV-infected patients with access to a computer and broadband were randomised to be monitored either through Virtual Hospital (Arm I) or through standard care at the day hospital (Arm II). After one year of follow up, patients switched their care to the other arm. Virtual Hospital offered four main services: Virtual Consultations, Telepharmacy, Virtual Library and Virtual Community. A technical and clinical evaluation of Virtual Hospital was carried out. FINDINGS: Of the 83 randomised patients, 42 were monitored during the first year through Virtual Hospital (Arm I) and 41 through standard care (Arm II). Baseline characteristics of patients were similar in the two arms. The level of technical satisfaction with the virtual system was high: 85% of patients considered that Virtual Hospital improved their access to clinical data and they felt comfortable with the videoconference system. Neither clinical parameters [level of CD4+ T lymphocytes, proportion of patients with an undetectable level of viral load (p = 0.21) and compliance levels >90% (p = 0.58)] nor the evaluation of quality of life or psychological questionnaires changed significantly between the two types of care. CONCLUSIONS: Virtual Hospital is a feasible and safe tool for the multidisciplinary home care of chronic HIV patients. Telemedicine should be considered as an appropriate support service for the management of chronic HIV infection. TRIAL REGISTRATION: Clinical-Trials.gov: NCT01117675.
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Infecciones por VIH/terapia , VIH-1/fisiología , Servicios de Atención de Salud a Domicilio/normas , Nivel de Atención , Telemedicina/métodos , Adulto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Enfermedad Crónica , Femenino , Infecciones por VIH/virología , Humanos , Masculino , Telemedicina/instrumentación , Telemedicina/normas , Carga ViralRESUMEN
Acute hepatitis C (AHC) is an increasing health issue. Despite the decline of blood-to-blood transmission of hepatitis C virus (HCV) through donor screening programs and a decline in intravenous drug use, the incidence of sexual transmission has now increased, particularly in HIV-infected homosexual patients. The presentation is almost always asymptomatic, which complicates diagnosis. Spontaneous clearance of the virus occurs in 25% of cases and usually, within the first three months after onset of symptoms and in symptomatic patients. If serum HCV-RNA remains detectable after this period, antiviral treatment should be started without delay, since sustained viral response rate in the acute phase is higher than that achieved with chronic liver disease. The optimal treatment regimen (interferon alone or combined with ribavirin) and its duration are not clearly established at the present time.
Asunto(s)
Hepatitis C/epidemiología , Enfermedad Aguda , Antivirales/uso terapéutico , Enfermedades Asintomáticas , Comorbilidad , Femenino , Infecciones por VIH/epidemiología , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/prevención & control , Hepatitis C/transmisión , Humanos , Interferón-alfa/uso terapéutico , Masculino , ARN Viral/sangre , Ribavirina/uso terapéutico , Factores de Riesgo , Conducta Sexual , España/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Viremia/diagnóstico , Viremia/epidemiologíaRESUMEN
BACKGROUND: Switching to raltegravir in selected patients treated with ritonavir-boosted protease inhibitors may result in similar efficacy and lower plasma lipids. METHODS: SPIRAL is a 48-week multicentre, open-label trial in which HIV-infected adults with less than 50 copies/ml of plasma HIV RNA for at least the previous 6 months on ritonavir-boosted protease inhibitor-based therapy were randomized (1: 1) to switch from the ritonavir-boosted protease inhibitor to raltegravir or to continue on ritonavir-boosted protease inhibitor-based therapy. Primary endpoint was the proportion of patients free of treatment failure (noncompleter = failure) at 48 weeks. SPIRAL study was powered to show noninferior efficacy of raltegravir-based therapy with a margin of -12.5%. RESULTS: Two hundred and seventy-three patients assigned to switch to raltegravir (n = 139) or to continue ritonavir-boosted protease inhibitor (n = 134) were included in the efficacy analysis. At 48 weeks, 89.2% (raltegravir-based therapy) and 86.6% (ritonavir-boosted protease inhibitor-based therapy) of the patients remained free of treatment failure [difference 2.6%; 95% confidence interval (CI) -5.2 to 10.6]. A total of 96.9% (raltegravir-based therapy) and 95.1% (ritonavir-boosted protease inhibitor-based therapy) of the patients remained free of virological failure (difference 1.8%; 95% CI -3.5 to 7.5). Switching to raltegravir was associated with significant decreases in plasma lipids and total-to-HDL cholesterol ratio relative to continuing ritonavir-boosted protease inhibitor. Severe adverse events and study drug discontinuations due to any adverse event occurred in 4 and 2% of the patients in each group. CONCLUSION: In patients with sustained virological suppression on ritonavir-boosted protease inhibitor-based therapy, switching from ritonavir-boosted protease inhibitor to raltegravir demonstrated noninferior efficacy and resulted in a better lipid profile at 48 weeks than continuing ritonavir-boosted protease inhibitor.
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Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/aislamiento & purificación , Pirrolidinonas/uso terapéutico , Ritonavir/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Terapia Antirretroviral Altamente Activa/métodos , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Inhibidores de Integrasa VIH/efectos adversos , Inhibidores de la Proteasa del VIH/efectos adversos , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Pirrolidinonas/efectos adversos , ARN Viral/sangre , Raltegravir Potásico , Ritonavir/efectos adversos , Resultado del Tratamiento , Carga ViralRESUMEN
OBJECTIVE: To assess the effects of initiating abacavir-containing therapy on plasma lipids and cardiovascular biomarkers. DESIGN: Sub-study of the BICOMBO study in which participants were randomized to switch their nucleoside backbone to either abacavir/lamivudine or tenofovir/emtricitabine. METHODS: We assessed 48-week changes in fasting lipids and several biomarkers including serum high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), osteoprotegerin, interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), selectin E and P, adiponectin, insulin, and D-dimer in otherwise healthy, virologically suppressed HIV-infected patients randomly switched to abacavir/lamivudine or tenofovir/emtricitabine with no history of cardiovascular disease, no prior abacavir or tenofovir use, and no virological failure or AIDS during follow-up. RESULTS: Eighty (46 abacavir/lamivudine and 34 tenofovir/emtricitabine) patients were included. Baseline characteristics were similar between groups and between patients in the sub-study vs. those not. There were no significant differences in baseline lipids and markers between groups. Although total (6.5 vs. -6.7%, P < 0.0001) and low-density lipoprotein (LDL) (8.6 vs. -9.1%, P = 0.004) cholesterol increased significantly in the abacavir/lamivudine group relative to the tenofovir/emtricitabine group, we found no significant changes in the biomarkers: CRP (-3.9 vs. 0.0%), MCP-1 (5.9 vs. 4.0%), osteoprotegerin (5.1 vs. -2.8%), IL-6 (0.0 vs. 0.0%), IL-10 (0.0 vs. 0.0%), TNF-alpha (0.0 vs. 0.0%), ICAM-1 (6.6 vs. 5.2%), VCAM-1 (0.02 vs. -0.01%), selectin E (-0.4 vs. 7.8%), selectin P (4.6 vs. 12.6%), insulin (-2.5 vs. 8.8%), adiponectin (-2.2 vs. 15.4%), and D-dimer (0.0 vs. 0.0%) (P > or = 0.12 for all comparisons). CONCLUSION: Abacavir/lamivudine increased total and LDL cholesterol compared with tenofovir/emtricitabine, but it did not cause inflammation, endothelial dysfunction, insulin resistance, or hypercoagulability in virologically suppressed HIV-infected patients.
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Fármacos Anti-VIH/administración & dosificación , Enfermedades Cardiovasculares/sangre , Didesoxinucleósidos/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Inhibidores de la Transcriptasa Inversa/administración & dosificación , Adenina/administración & dosificación , Adenina/análogos & derivados , Adulto , Fármacos Anti-VIH/efectos adversos , Biomarcadores/sangre , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Didesoxinucleósidos/efectos adversos , Quimioterapia Combinada , Emtricitabina , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/virología , Humanos , Lamivudine/administración & dosificación , Lípidos/sangre , Masculino , Persona de Mediana Edad , Organofosfonatos/administración & dosificación , Inhibidores de la Transcriptasa Inversa/efectos adversos , Tenofovir , Resultado del Tratamiento , Carga ViralRESUMEN
PURPOSE OF REVIEW: With effective antiretroviral therapy, cardiovascular disease has gained importance as a cause of morbidity and mortality in HIV-infected persons. We review the risk of cardiovascular disease in HIV-infected persons compared with that in uninfected persons and discuss the relative contributions of host, HIV, and antiretroviral therapy in the light of current knowledge. RECENT FINDINGS: The incidence of cardiovascular disease in HIV-infected patients receiving antiretroviral therapy is low. However, the risk of cardiovascular disease increased compared with that in uninfected persons. This fact is substantially due to a higher prevalence of underlying traditional cardiovascular risk factors that are mostly host dependent. HIV may additionally contribute both directly through immune activation and inflammation, and indirectly through immunodeficiency. In a more modest way than that of HIV infection, the type of antiretroviral therapy may also contribute through its impact on metabolic and body fat parameters, and possibly through other factors that are currently unclear. SUMMARY: Prevention of cardiovascular disease in HIV-infected patients should be standard of care. Traditional risk factors should be investigated and aggressively treated when possible. Antiretroviral therapy should be initiated earlier in patients with high cardiovascular risk. From a purely cardiovascular perspective, the benefits of antiretroviral therapy clearly outweigh any potential risk.
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Terapia Antirretroviral Altamente Activa , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Factores de Riesgo , Manejo de Caso , HumanosRESUMEN
BACKGROUND: CD4+ T cell recovery dynamics were analysed during the 'on treatment' periods in structured therapy interruption (STI) as well as the long-term immune reconstitution with highly active antiretroviral therapy (HAART) after finishing STI. METHODS: One hundred and twenty HIV-1-infected patients on successful HAART were randomized to receive for 2 years continuous HAART (n=37) or two different strategies of STI (n=83). After this period, most patients received continuous HAART for 2 years. RESULTS: During the STI period, the rate of recovery of CD4+ T cells decreased progressively from the first to the last resumption of HAART {median change of increase: +232 [interquartile range (IQR): +126, +318], +116 (IQR: +10, +471), +87 (IQR: -54, +252) and -26 (IQR: -352, +211) cells/mm3 after the first, second, third and fourth resumption, respectively}. After the STI period and 2 years of continuous HAART, the median CD4+ count remained significantly lower than at baseline in STI arms, both in the virological arm [559 (IQR: 383, 727) versus 771 (IQR: 625, 913) cells/mm3, P<0.0001] and the immunological arm [619 (IQR: 501, 789) versus 787 (IQR: 657, 954) cells/mm3, P<0.0001], but not in the control arm [886 (IQR: 564, 1122) versus 780 (IQR: 539, 945) cells/mm3, P=0.68]. In a multivariate analysis, the nadir of CD4+ T cells and the baseline value of CD4+ before the STI period independently predicted the level of CD4+ T cells 2 years after resumption of HAART (in both cases, P<0.0001). CONCLUSION: The drop in CD4+ cell count after a first and a second period of 3 months of interruption of HAART was completely recovered after resuming HAART; conversely, interruptions longer than 6 months were deleterious for the recovery of CD4+. CD4+ cell count did not rebound completely in patients who received 2 years of HAART after 2 years of STIs.
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Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Privación de Tratamiento , Adulto , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
UNLABELLED: Although two pegylated interferons (Peg-IFN) are available to treat chronic hepatitis C virus (HCV) infection, no head-to-head comparative studies have been published. We aim to compare the efficacy and safety of PEG IFN alfa-2b (PEG 2b) versus PEG IFN alfa-2a (PEG 2a), plus ribavirin (RBV). A prospective, randomized, multi-center, open-label clinical trial including 182 human immunodeficiency virus (HIV)-hepatitis C virus (HCV) patients naïve for HCV therapy was performed. Patients were assigned to PEG 2b (80-150 mug/week; n = 96) or PEG 2a (180 mug/week; n = 86), plus RBV (800-1200 mg/day) for 48 weeks. The primary endpoint was sustained virological response (SVR: negative HCV-RNA 24 weeks after completion of treatment). At baseline, both groups were well balanced: 73% male; 63% HCV genotype 1 or [corrected] 4; 29% had fibrosis index of 3 or greater. The overall SVR was 44% (42% PEG 2b versus 46% PEG 2a, P = 0.65). Among genotypes 1 or [corrected] 4, SVRs were 28% versus 32% (P = 0.67) and 62% versus 71% (P = 0.6) in genotypes 2 or [corrected] 3 for PEG 2b and PEG 2a, respectively. Early virological response (EVR; >or=2 log reduction from baseline or negative HCV-RNA at week 12) was 70% in the PEG 2b group and 80% in the PEG 2a group (P = 0.13), reaching a positive predictive value of SVR of 64% and a negative predictive value of 100% in both arms. Side effects were present in 96% of patients but led to treatment discontinuation in 10% of patients (8% on PEG 2b and 13% on PEG 2a, P = 0.47). CONCLUSION: In patients with HIV, HCV therapy with PEG 2b or PEG 2a plus RBV had no significant differences in efficacy and safety.
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Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Polietilenglicoles/administración & dosificación , Ribavirina/administración & dosificación , Adulto , Quimioterapia Combinada , Femenino , Infecciones por VIH/complicaciones , Hepatitis C Crónica/etiología , Humanos , Interferón alfa-2 , Interferón-alfa/efectos adversos , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Proteínas RecombinantesRESUMEN
BACKGROUND: Hypertension has been related to endothelial dysfunction. Patients with refractory hypertension (RH) have a reduced number of endothelial progenitor cells (EPCs). AIM: To evaluate if blood EPC levels relate to endothelium-dependent vasodilation (ED-VD) in RH. METHODS: We analyzed 29 RH confirmed by 24-h ambulatory blood pressure monitoring and assessed complete clinical and laboratory evaluation. EPCs were isolated from peripheral mononuclear cells (MNC) by flow cytometry. ED-VD was determined measuring flow-mediated dilation (FMD) by venous occlusion plethysmography. Results. Circulating EPCs/10(5) MNC (median [Q1-Q3]): 23.0 [4.5-53.8]. FMD (median [Q1-Q3]): 211.7 [79.5-365.8]%. Significant correlations with log-FMD: EPCs (r = 0.469; p = 0.018) and homocysteine (r = -0.414; p = 0.045). There was no collinearity between EPCs and homocysteine. FMD did not correlate with age, gender, office BP, 24-h systolic blood pressure or 24-h diastolic blood pressure, laboratory parameters, C-reactive-protein, left ventricular-mass index, dyslipidaemia, smoking habit and statin or angiotensin system blockers treatment. Multiple linear regression analysis showed that after age-adjustment, EPC (p = 0.027) and homocysteine (p = 0.004) were the only variables that predicted FMD (R = 0.740). After dividing patients according to EPC number, patients in the lower tertile showed a significantly reduced FMD compared with those in the group of the two upper tertiles of EPC: log-FMD (mean+/-SD): 4.7+/-0.9 vs 5.6+/-0.8, respectively (p = 0.031). CONCLUSIONS: ED-VD independently correlates with circulating EPCs in RH. Homocysteine is also an independent predictor of lower FMD in such patients.
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Dilatación Patológica/diagnóstico , Células Endoteliales/patología , Hipertensión/patología , Células Madre/patología , Adulto , Recuento de Células , Separación Celular , Dilatación Patológica/patología , Citometría de Flujo , Homocisteína/sangre , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Análisis de Regresión , VasodilataciónRESUMEN
Occult hepatitis B virus (HBV) infection is diagnosed when HBc antibodies (HBcAb) and HBV DNA are detectable in serum while hepatitis B surface antigen (HBsAg) is not. This situation has been frequently described in patients with chronic hepatitis C virus (HCV) infection. The objective of this study was to evaluate the prevalence of occult hepatitis B in HIV-HCV-coinfected patients and its clinical relevance in liver histology and viral response after interferon therapy for HCV. A total of 238 HIV-HCV-infected patients,negative for HBsAg, were included. Serum samples were analyzed for the presence of HBV DNA and HBcAb.HBV DNA quantification was determined with the Cobas TaqMan HBV Test (detection limit 6 IU/ml). Data from liver biopsy and laboratory tests were also analyzed. HBcAb resulted in 142 (60%) patients, being the independent associated factors: male gender, previous history of intravenous drug use, age, CD4 count,and HAV antibody presence. Among 90 HBcAb patients that we could analyze, HBV DNA was positive in 15 (16.7% of occult hepatitis B infection in this group, and 6.3% in the whole HIV-HCV cohort studied). No baseline factors, liver histology, or HCV therapy response were related to the presence of HBV DNA. We found that occult hepatitis B is a frequent condition present in at least 6.3% of our HCV-HIV patients and in more than 16% of those with HBcAb. Despite the high prevalence, this phenomenon does not seem to affect the clinical evolution of chronic hepatitis C or modify the viral response to interferon-based HCV therapies
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Antivirales/farmacología , ADN Viral/sangre , Infecciones por VIH , VIH , Anticuerpos Antihepatitis/sangre , Antígenos del Núcleo de la Hepatitis B/inmunología , Virus de la Hepatitis B , Hepatitis B/epidemiología , Hepatitis B/patología , Hepatitis C Crónica/tratamiento farmacológico , Interferones/uso terapéutico , Cirrosis Hepática/diagnóstico , Adulto , Biopsia , Estudios de Cohortes , Comorbilidad , Progresión de la Enfermedad , Femenino , Infecciones por VIH/tratamiento farmacológico , Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/inmunología , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Hígado/patología , Masculino , Prevalencia , Estudios Retrospectivos , España/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND: Stavudine (d4T)-containing regimens are associated with a potential for lipoatrophy and dyslipidaemia. We assessed the safety and efficacy of reducing the dose of stavudine compared with switching to tenofovir or maintaining the standard dose of d4T. METHODS: Clinically stable HIV-infected patients receiving antiretroviral therapy containing stavudine 40 mg twice daily with a plasma HIV RNA < 200 copies/ml for at least 6 months were randomized to maintain stavudine 40 mg twice daily (d4T40 arm), to reduce to 30 mg twice daily (d4T30 arm), or to switch from d4T to tenofovir (TDF arm). RESULTS: Fifty-eight (93% male) patients were included: 22 in the d4T40 arm, 19 in the d4T30 arm and 17 in TDF arm. At baseline, median time on d4T was 6 years (interquartile range [IQR] 2.6-7.1), median age 43 years (IQR 36-51) and median CD4+ T-cell count was 587/mm3 (IQR 329-892). At week 24, median limb fat changes (g) were as follows: d4T40 = -182 (95% CI: -469- -5); d4T30 = 527 (95% CI: -343-694); and TDF = 402 (95% CI: 130-835; d4T40 versus TDF, P = 0.0003). Significant differences between median values of laboratory parameters were detected: triglycerides (mg/dl): d4T40 = 19; d4T30 = -23 and TDF = -79 (d4T40 versus TDF, P = 0.03); and total cholesterol (mg/dl): d4t40 = 22, d4T30 = -4, and TDF = -28 (d4T40 versus TDF, P = 0.04). No significant difference was observed in mitochondrial function assessed in peripheral blood mononuclear cells. CONCLUSIONS: Although both strategies were associated with a trend toward a decrease in plasma lipids and an increase in body fat, the only significant changes were observed among those who switched to tenofovir.
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Adenina/análogos & derivados , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH , Organofosfonatos/uso terapéutico , Estavudina/uso terapéutico , Adenina/uso terapéutico , Adulto , Fármacos Anti-VIH/efectos adversos , Composición Corporal , Colesterol/sangre , Esquema de Medicación , Femenino , Infecciones por VIH/sangre , Humanos , Leucocitos Mononucleares/metabolismo , Lipodistrofia/inducido químicamente , Masculino , Persona de Mediana Edad , Mitocondrias/metabolismo , Consumo de Oxígeno , Estavudina/efectos adversos , Tenofovir , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
BACKGROUND: Several serum markers reflecting extracellular matrix status have been correlated with liver fibrosis in non-HIV-infected patients with chronic hepatitis C infection. These indexes have been less examined in HIV/HCV-coinfected individuals. OBJECTIVE: We aimed to evaluate the predictive value of serum markers for liver fibrosis in HIV-infected patients with chronic hepatitis C virus (HVC). METHODS: Serum levels of metalloproteinases 1 and 2 (MMP-1 and -2), tissue inhibitors of matrix metalloproteinases (TIMP-1), procollagen type III N-terminal peptide (PIIINP), and hyaluronic acid (HA) were measured in HIV-infected patients with chronic hepatitis C at the time of obtaining a liver biopsy and before the consideration of anti-hepatitis C therapy. RESULTS: One hundred and nineteen consecutive HIV-HVC coinfected patients were included. TIMP-1 (r = 0.6; P < 0.001), TIMP-1/MMP-1 ratio (r = 0.5; P < 0.001), TIMP-1/MMP-2 ratio (r = 0.3; P < 0.001), MMP-2 (r = 0.2; P = 0.044), PIIINP (r = 0.4; P < 0.001), and HA (r = 0.5; P < 0.001) were positively and significantly correlated with the fibrosis stage. In the multivariate analysis, TIMP-1 (odds ratio [OR] = 1.004, 95% confidence interval [CI]: 1.002 to 1.006, P = 0.001) and HA >95 microg/dL (OR = 6.041, 95% CI: 1.184 to 30.816, P = 0.031) were independently associated with liver fibrosis. The area under the curve of score to discriminate mild (F0-F1) from significant (F2-F4) fibrosis in the received-operating analysis using the variables TIMP-1 and HA was 0.84, with a sensitivity of 72.9% and a specificity of 83.1%. CONCLUSION: TIMP-1 and HA were quite sensitive and specific for predicting the degree of liver fibrosis in HIV-infected patients with chronic hepatitis C. These parameters may become a noninvasive alternative to liver biopsy when the degree of liver fibrosis needs to be estimated.