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Plasma extracellular vesicle (EV)-associated cytokines were quantified in people with HIV (PWH) with different virological control status, including elite controllers (EC) who maintain persistent control (PC) or not (TC). Cytokine signatures and pathways were determined for each group. Median EV-associated cytokine levels were higher among PWH than HIV-uninfected. EC showed the highest levels of EV-associated cytokines among PWH with PC levels higher than TC levels. IL-18 levels best distinguished PWH from uninfected controls, and EC from ART-treated, and IL-3 distinguished PC from TC. The role of EV-cytokines in intercellular communication and endogenous control of HIV expression should be investigated further.
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Vesículas Extracelulares , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , VIH-1/metabolismo , Interleucina-18/metabolismo , Interleucina-3 , Linfocitos T CD4-Positivos/metabolismo , Citocinas/metabolismo , Biomarcadores , Vesículas Extracelulares/metabolismoRESUMEN
People living with HIV (PLWH) are prioritised for SARS-CoV-2 vaccination due to their vulnerability to severe COVID-19. Therefore, the epidemiological surveillance of vaccination coverage and the timely identification of suboptimally vaccinated PLWH is vital. We assessed SARS-CoV-2 vaccination coverage and factors associated with under-vaccination among PLWH in Catalonia, Spain. As of 11.12.2021, 9945/14942 PLWH (66.6%) had received ≥1 dose of a SARS-CoV-2 vaccine. Non-Spanish origin (adjusted odds ratio (aOR) 0.64, 95% CI 0.59−0.70), CD4 count of 200−349 cells/µL (aOR 0.74, 95% CI 0.64−0.86) or 350−499 cells/µL (aOR 0.79, 95% CI 0.70−0.88), detectable plasma HIV-RNA (aOR 0.61 95% CI 0.53−0.70), and previous SARS-CoV-2 diagnosis (aOR 0.58 95% CI 0.51−0.65) were associated with under-vaccination. SARS-CoV-2 diagnosis (437 [9.5%] vs. 323 [3.5%], p < 0.001), associated hospitalisations (10 [2.3%] vs. 0 [0%], p < 0.001), intensive care unit admissions (6 [1.4%] vs. 0 [0%], p < 0.001), and deaths (10 [2.3%] vs. 0 [0%], p < 0.001) were higher among unvaccinated PLWH. Vaccination coverage was lower among PLWH with a CD4 count >200 cells/µL, detectable plasma HIV-RNA, previous SARS-CoV-2 diagnosis, and migrants. SARS-CoV-2 diagnosis, associated hospitalisations, and deaths among PLWH were lower among the vaccinated compared with the unvaccinated. SARS-CoV-2 vaccination prioritisation has not completely reached vulnerable PLWH with poorer prognosis. This information can be used to inform public health strategies.
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Background: The epidemiological situation generated by COVID-19 has cast into sharp relief the delicate balance between public health priorities and the economy, with businesses obliged to toe the line between employee health and continued production. In an effort to detect as many cases as possible, isolate contacts, cut transmission chains, and limit the spread of the virus in the workplace, mass testing strategies have been implemented in both public health and industrial contexts to minimize the risk of disruption in activity. Objective: To evaluate the economic impact of the mass workplace testing strategy as carried out by a large automotive company in Catalonia in terms of health and healthcare resource savings. Methodology: Analysis of health costs and impacts based on the estimation of the mortality and morbidity avoided because of screening, and the resulting savings in healthcare costs. Results: The economic impact of the mass workplace testing strategies (using both PCR and RAT tests) was approximately 10.44 per test performed or 5575.49 per positive detected; 38% of this figure corresponds to savings derived from better use of health resources (hospital beds, ICU beds, and follow-up of infected cases), while the remaining 62% corresponds to improved health rates due to the avoided morbidity and mortality. In scenarios with higher positivity rates and a greater impact of the infection on health and the use of health resources, these results could be up to ten times higher (130.24 per test performed or 69,565.59 per positive detected). Conclusion: In the context of COVID-19, preventive actions carried out by the private sector to safeguard industrial production also have concomitant public benefits in the form of savings in healthcare costs. Thus, governmental bodies need to recognize the value of implementing such strategies in private settings and facilitate them through, for example, subsidies.
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COVID-19 , Prueba de COVID-19 , Costos de la Atención en Salud , Humanos , SARS-CoV-2 , Lugar de TrabajoRESUMEN
BACKGROUND: The combination of boosted darunavir plus rilpivirine, once daily, could be a convenient, effective and well-tolerated two-drug regimen to achieve HIV suppression in HIV-infected patients. METHODS: Multicentre, retrospective cohort study in nine hospitals in Spain. All HIV-infected subjects starting boosted darunavir plus rilpivirine were included, irrespective of their viral load (VL). The primary objective was the percentage of patients with VL <50â copies/mL at 48 weeks. Secondary objectives included changes in CD4+ cell count, lipid profile and renal function. RESULTS: Eighty-one of 84 patients reached Week 48. Fifty-nine (70.2%) patients had VL <50â copies/mL at baseline and the rest had a median VL of 202 (IQR 98-340) copies/mL. Subjects had a median of 21 years of infection with six prior regimens. The main reasons for starting boosted darunavir plus rilpivirine were simplification (44%), kidney or bone toxicity (28.6%) and virological failure (17.9%). Historical genotypes from 47 patients showed 41 (87.2%) patients with NRTI RAMs, 21 (44.7%) with NNRTI RAMs, 12 (25.5%) with primary PI RAMs and 7 (14.9%) with integrase strand transfer inhibitor (INSTI) RAMs. One patient had low-level resistance to boosted darunavir and five patients had some resistance to rilpivirine. At 48 weeks, 71 (87.7%) patients had VL <50â copies/mL. According to undetectable or detectable baseline VL, effectiveness was 91.1% or 80%, respectively. There were four virological failures with no emergence of new RAMs. Three of these patients resuppressed viraemia while maintaining the same regimen. CONCLUSIONS: The combination of boosted darunavir plus rilpivirine has shown good effectiveness and tolerability in this cohort of pretreated patients with a long-lasting HIV infection, exposure to multiple antiretroviral regimens and prior HIV resistance.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Fármacos Anti-VIH/uso terapéutico , Darunavir/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Rilpivirina/uso terapéutico , Ritonavir/uso terapéutico , España , Carga ViralAsunto(s)
Encéfalo/patología , Infecciones por VIH/complicaciones , Síndrome Inflamatorio de Reconstitución Inmune/diagnóstico , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Adulto , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Síndrome Inflamatorio de Reconstitución Inmune/patología , Leucoencefalopatía Multifocal Progresiva/patología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The financing of antiretroviral therapy (ART) is generally determined by the cost incurred in the previous year, the number of patients on treatment, and the evidence-based recommendations, but not the clinical characteristics of the population. OBJECTIVE: To establish a score relating the cost of ART and patient clinical complexity in order to understand the costing differences between hospitals in the region that could be explained by the clinical complexity of their population. METHODS: Retrospective analysis of patients receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially associated with a higher cost of ART were assessed by bivariate and multivariate analysis. Two predictive models of 'high-cost' were developed. The normalized estimated (adjusted for the complexity scores) costs were calculated and compared with the normalized real costs. RESULTS: In the Hospital Index, 631 (16.8%) of the 3758 patients receiving ART were responsible for a "high-cost" subgroup, defined as the highest 25% of spending on ART. Baseline variables that were significant predictors of high cost in the Clinic-B model in the multivariate analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality, year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was lower than the overall mean value of the four hospitals (6.16). CONCLUSIONS: The clinical complexity of the HIV patient influences the cost of ART. The Clinic-B and Clinic-BF scores predicted patients with high cost of ART and could be used to compare and allocate costs corrected for the patient clinical complexity
ANTECEDENTES: La financiación de la terapia antirretroviral (ART) se determina generalmente por los costos incurridos en el año anterior, el número de pacientes en tratamiento y las recomendaciones basadas en la evidencia, pero no por las características clínicas de la población. OBJETIVO: Establecer un índice que relacione el coste de ART y los pacientes de elevada complejidad clínica con el fin de entender las diferencias de coste entre los hospitales de la región que podrían explicarse por la diferente complejidad clínica de sus poblaciones. MÉTODOS: Análisis retrospectivo de los pacientes que reciben TAR en un hospital terciario entre 2009 y 2011. Los factores potencialmente asociados con un mayor coste de TAR se evaluaron mediante análisis bivariado y multivariado. Se desarrollaron dos modelos de predicción de 'coste elevado'. Se calculó el coste estimado normalizado (ajustado por el índice de complejidad) y se comparó con el coste real normalizado. RESULTADOS: En el hospital índice, 631 (16.8%) de los 3.758 pacientes que recibieron TAR asumió "coste elevado", definido como el 25% más alto del gasto en TAR. Las variables basales que fueron asociadas a alto coste en el modelo Clínic-B en el análisis multivariado fueron: vía de transmisión del VIH, criterios de sida, nacionalidad española, año de inicio del TAR, nadir de CD4+ y número de ingresos hospitalarios. El índice de complejidad Clínic-B varió de 0 a 13 puntos, y el valor medio (5.97) fue menor que el valor medio global de los cuatro hospitales (6.16). CONCLUSIONES: La complejidad clínica de los pacientes VIH influye en el coste de la TAR. Las puntuaciones Clínic-B y Clínic-BF predijeron los pacientes con alto costo de TAR y podrían utilizarse para comparar y asignar costes corregidos según la complejidad clínica de los pacientes
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Humanos , Infecciones por VIH/tratamiento farmacológico , Antirretrovirales/economía , Terapia Antirretroviral Altamente Activa/economía , Costo de Enfermedad , Costos de la Atención en Salud/estadística & datos numéricos , Estudios Retrospectivos , Técnicas de Apoyo para la Decisión , Modelos LogísticosRESUMEN
BACKGROUND: The financing of antiretroviral therapy (ART) is generally determined by the cost incurred in the previous year, the number of patients on treatment, and the evidence-based recommendations, but not the clinical characteristics of the population. OBJECTIVE: To establish a score relating the cost of ART and patient clinical complexity in order to understand the costing differences between hospitals in the region that could be explained by the clinical complexity of their population. METHODS: Retrospective analysis of patients receiving ART in a tertiary hospital between 2009 and 2011. Factors potentially associated with a higher cost of ART were assessed by bivariate and multivariate analysis. Two predictive models of "high-cost" were developed. The normalized estimated (adjusted for the complexity scores) costs were calculated and compared with the normalized real costs. RESULTS: In the Hospital Index, 631 (16.8%) of the 3758 patients receiving ART were responsible for a "high-cost" subgroup, defined as the highest 25% of spending on ART. Baseline variables that were significant predictors of high cost in the Clinic-B model in the multivariate analysis were: route of transmission of HIV, AIDS criteria, Spanish nationality, year of initiation of ART, CD4+ lymphocyte count nadir, and number of hospital admissions. The Clinic-B score ranged from 0 to 13, and the mean value (5.97) was lower than the overall mean value of the four hospitals (6.16). CONCLUSIONS: The clinical complexity of the HIV patient influences the cost of ART. The Clinic-B and Clinic-BF scores predicted patients with high cost of ART and could be used to compare and allocate costs corrected for the patient clinical complexity.
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Fármacos Anti-VIH/economía , Costos y Análisis de Costo , Infecciones por VIH/tratamiento farmacológico , Recuento de Linfocito CD4 , Infecciones por VIH/economía , Costos de la Atención en Salud , Humanos , Modelos Económicos , Estudios RetrospectivosRESUMEN
There are few data about the immunovirological efficacy, safety/tolerability, and durability of maraviroc (MVC) addition to aging patients on suppressive antiretroviral therapy (cART) and undetectable viral load (<50 copies/ml). The aging population is underrepresented in most HIV clinical trials. This study included 80 patients aged ≥50 years and 161 aged <50 years and showed that after 48 weeks of treatment, there was no between-group differences in the median increase of CD4(+) T cells or the virological suppression rate. Safety and tolerability were also comparable. In multivariable analysis, the effect of age was not modified and was independent of the response to MVC. An immunological recovery of ≥100 CD4(+) T cells was significantly less common in those with a longer HIV history (≥15 years) (OR 0.43; p=0.016) or having <200/mm(3) CD4(+) T cells at MVC initiation (OR 0.27; p=0.004). Meanwhile, achieving a CD4/CD8 ratio ≥0.5 at week 48 was less likely in those with CD4(+) T cell counts <200 at MVC initiation (OR 0.09; p<0.0001) or with a previous AIDS event (OR 0.43; p=0.028). In summary, the immunovirological efficacy, safety/tolerability, and durability of MVC addition in patients virologically suppressed were independent of the patient's age at treatment onset.
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Fármacos Anti-VIH , Terapia Antirretroviral Altamente Activa , Antagonistas de los Receptores CCR5 , Ciclohexanos , Infecciones por VIH , VIH , Triazoles , Adulto , Factores de Edad , Anciano , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/inmunología , Fármacos Anti-VIH/uso terapéutico , Antagonistas de los Receptores CCR5/efectos adversos , Antagonistas de los Receptores CCR5/inmunología , Antagonistas de los Receptores CCR5/uso terapéutico , Ciclohexanos/efectos adversos , Ciclohexanos/inmunología , Ciclohexanos/uso terapéutico , VIH/genética , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Maraviroc , Persona de Mediana Edad , Análisis Multivariante , ARN Viral/sangre , Estudios Retrospectivos , Resultado del Tratamiento , Triazoles/efectos adversos , Triazoles/inmunología , Triazoles/uso terapéutico , Carga ViralRESUMEN
In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation vary depending on the CD4+ T-lymphocyte count, the presence of opportunistic infections or comorbid conditions, age, and the efforts to prevent the transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise three drugs, namely, two nucleoside reverse transcriptase inhibitors (NRTI) and one drug from another family. Three of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further seven regimens, which are based on an INSTI, an non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with ritonavir (PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include three (or at least two) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Infecciones Oportunistas Relacionadas con el SIDA , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa , Lactancia Materna , Recuento de Linfocito CD4 , Comorbilidad , Contraindicaciones , Farmacorresistencia Viral , Sustitución de Medicamentos , Quimioterapia Combinada , Femenino , Infecciones por VIH/inmunología , VIH-1/efectos de los fármacos , VIH-2 , Humanos , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Carga Viral , Viremia/tratamiento farmacológicoRESUMEN
INTRODUCTION: No controlled clinical trials had studied the role of maraviroc (MRV) in fully suppressed patients (1). MATERIALS AND METHODS: MRV-cohort is an observational, retrospective, multicentric (27 sites) large cohort study of patients starting MRV in clinical practice under different circumstances, with at least 48 weeks of follow-up. For the present analysis we selected all those patients starting with an HIV-RNA<50 copies/mL. Demographics, baseline CD4 cell count, past history of antiretroviral treatment (ART), tropism, reasons for MRV use, MRV based therapy and change/end of MRV use were assessed. Paired analysis of lipid, hepatic and kidney profile changes and univariate and multivariate analyses of HIV-RNA<50 copies/mL at 48 weeks were explored. RESULTS: We included 247 out of 667 subjects from the entire cohort. At study entry, their median age was 47 years, 23% were women, 31% MSM, 49% had CDC category C, median CD4+ counts were 468 cells/mm(3), 46% were HCV+ and 4.5% AgHBs+. Tropism information was available in 197 (94% R5). Median length of prior ARTV was 10.7 years, with exposure to a median of three drug families. Main reasons for prescribing MRV were: toxicity 38%, inmunodiscordance 23%, simplification 19% and admission in a clinical trial 10.4%. MRV based therapies used were MRV+2NRTIs 9%, MRV+PI 46%, MRV+PI+other 40% and MRV+other 5%. At 48 weeks, 23% of patients had changed or finished MRV therapy due to toxicity 2.4%, virological failure 2%, immunological failure 1.2%, simplification 3,2%, trial requirement 9.7%, medical decision 2.8%, treatment suspension 1.2% and unknown 0.4%. At 48 weeks, no significant changes were observed in lipid, hepatic or kidney profiles, and 85% of patients remained with HIV-RNA<50 copies/mL. Focusing on viral response univariate and multivariate models did not show any significant baseline variable explaining viral failure. CONCLUSIONS: In clinical practice MRV was used, mostly in R5 positive patients, with adequate efficacy and tolerance, but important number of patients changed due to non-clinical reasons. In this scenario neither reason for use of MRV nor MRV-based therapy explained viral failure.
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BACKGROUND: There are conflicting data on the prevalence of coronary events and the quality of the management of modifiable cardiovascular risk factors (CVRF) in HIV-infected patients. METHODS: We performed a retrospective descriptive study to determine the prevalence of coronary events and to evaluate the management of CVRF in a Mediterranean cohort of 3760 HIV-1-infected patients from April 1983 through June 2011. RESULTS: We identified 81 patients with a history of a coronary event (prevalence 2.15%); 83% of them suffered an acute myocardial infarction. At the time of the coronary event, CVRF were highly prevalent (60.5% hypertension, 48% dyslipidemia, and 16% diabetes mellitus). Other CVRF, such as smoking, hypertension, lack of exercise, and body mass index, were not routinely assessed. After the coronary event, a significant decrease in total cholesterol (P = 0.025) and LDL-cholesterol (P = 0.004) was observed. However, the percentage of patients who maintained LDL-cholesterol > 100 mg/dL remained stable (from 46% to 41%, P = 0.103). Patients using protease inhibitors associated with a favorable lipid profile increased over time (P = 0.028). CONCLUSIONS: The prevalence of coronary events in our cohort is low. CVRF prevalence is high and their management is far from optimal. More aggressive interventions should be implemented to diminish cardiovascular risk in HIV-infected patients.
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Infecciones por VIH/complicaciones , Hipertensión/epidemiología , Hipertensión/patología , Isquemia Miocárdica/epidemiología , Anciano , Colesterol/sangre , Femenino , Infecciones por VIH/virología , VIH-1/patogenicidad , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/patología , Factores de RiesgoRESUMEN
OBJECTIVE: To analyze the effect of switching the ritonavir-boosted protease inhibitor (PI/r) in a stable combined antiretroviral therapy (cART) regimen to raltegravir on low-density lipoprotein (LDL) particles, and lipoprotein-associated phospholipase A2 (Lp-PLA2). DESIGN: Substudy of a multicenter randomized trial that compared the efficacy of switching a PI/r to raltegravir-based cART in stable HIV-infected patients. METHODS: LDL size and phenotype (by gel-gradient electrophoresis), Lp-PLA2 (by 2-thio-PAF [Cayman]), proprotein convertase subtilisin/kexin type 9 (PCSK9) (by ELISA), and standard lipid parameters were measured at baseline and week 48. RESULTS: Eighty-one (PI/r n = 41 and raltegravir n = 40) patients were evaluated. No differences in baseline demographic and metabolic variables between arms were found except in apolipoprotein (Apo) B (p = 0.042). At week 48, total cholesterol (TC) (p < 0.001), LDL-c (p = 0.023), non-high density lipoprotein cholesterol non-high-density lipoprotein cholesterol (non-HDL-c) (p < 0.001), TC/HDL (p = 0.026), triglyceride (p < 0.001), Apo B (p < 0.001), Apo A-I (p = 0.004) and Lp (a) (p = 0.005) decreased in raltegravir arm compared to PI/r arm. At week 48, a shift from LDL phenotype B to the less atherogenic phenotype A was observed only in raltegravir arm (p < 0.001). LDL size increased (PI/r 2.1 nm, p = 0.019; raltegravir 3.8 nm, p = 0.001) and cholesterol content in small and dense LDL subfractions (LDL 4,5,6) decreased (PI/r p = 0.007, raltegravir p = 0.006) at week 48 in both arms. Total Lp-PLA2 activity (PI/r p = 0.037 and raltegravir p = 0.051) and PCSK9 plasma concentration decreased in both arms (PI/r p = 0.034 and raltegravir p < 0.001). CONCLUSIONS: Switching a PI/r to a raltegravir-based cART in virologically suppressed HIV-infected patients was associated with an overall improvement in lipid profile, including a shift to a less atherogenic LDL phenotype.
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1-Alquil-2-acetilglicerofosfocolina Esterasa/metabolismo , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , Lípidos/sangre , Pirrolidinonas/administración & dosificación , Adulto , Anciano , LDL-Colesterol/sangre , Femenino , Infecciones por VIH/sangre , Humanos , Lipoproteínas LDL/metabolismo , Masculino , Persona de Mediana Edad , Raltegravir PotásicoRESUMEN
BACKGROUND: Thymidine analogue resistance mutations (TAMs) selected under treatment with nucleoside analogues generate two distinct genotypic profiles in the HIV-1 reverse transcriptase (RT): (i) TAM1: M41L, L210W and T215Y, and (ii) TAM2: D67N, K70R and K219E/Q, and sometimes T215F. Secondary mutations, including thumb subdomain polymorphisms (e.g. R284K) have been identified in association with TAMs. We have identified mutational clusters associated with virological failure during salvage therapy with tenofovir/emtricitabine-based regimens. In this context, we have studied the role of R284K as a secondary mutation associated with mutations of the TAM1 complex. RESULTS: The cross-sectional study carried out with > 200 HIV-1 genotypes showed that virological failure to tenofovir/emtricitabine was strongly associated with the presence of M184V (P < 10-10) and TAMs (P < 10-3), while K65R was relatively uncommon in previously-treated patients failing antiretroviral therapy. Clusters of mutations were identified, and among them, the TAM1 complex showed the highest correlation coefficients. Covariation of TAM1 mutations and V118I, V179I, M184V and R284K was observed. Virological studies showed that the combination of R284K with TAM1 mutations confers a fitness advantage in the presence of zidovudine or tenofovir. Studies with recombinant HIV-1 RTs showed that when associated with TAM1 mutations, R284K had a minimal impact on zidovudine or tenofovir inhibition, and in their ability to excise the inhibitors from blocked DNA primers. However, the mutant RT M41L/L210W/T215Y/R284K showed an increased catalytic rate for nucleotide incorporation and a higher RNase H activity in comparison with WT and mutant M41L/L210W/T215Y RTs. These effects were consistent with its enhanced chain-terminated primer rescue on DNA/DNA template-primers, but not on RNA/DNA complexes, and can explain the higher fitness of HIV-1 having TAM1/R284K mutations. CONCLUSIONS: Our study shows the association of R284K and TAM1 mutations in individuals failing therapy with tenofovir/emtricitabine, and unveils a novel mechanism by which secondary mutations are selected in the context of drug-resistance mutations.
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Adenina/análogos & derivados , Desoxicitidina/análogos & derivados , Farmacorresistencia Viral , Infecciones por VIH/virología , Transcriptasa Inversa del VIH/genética , VIH-1/genética , Mutación Missense , Organofosfonatos/administración & dosificación , Adenina/administración & dosificación , Adenina/farmacología , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/farmacología , Desoxicitidina/administración & dosificación , Desoxicitidina/farmacología , Emtricitabina , Infecciones por VIH/tratamiento farmacológico , Transcriptasa Inversa del VIH/metabolismo , VIH-1/efectos de los fármacos , VIH-1/aislamiento & purificación , Humanos , Datos de Secuencia Molecular , Organofosfonatos/farmacología , Selección Genética , Análisis de Secuencia de ADN , Tenofovir , Insuficiencia del TratamientoRESUMEN
The approval of maraviroc (Selzentri®), the first CCR5 antagonist, with specific antiviral activity against CCR5 (R5)-tropic HIV variants, has promoted the determination of HIV coreceptor usage in the clinical setting. The phenotypic assay Trofile™, which is based on recombinant virus technology, has been the most widely used diagnostic test, given that it was the only assay which provided tropism information in the pivotal maraviroc clinical trials. However, this method displays logistical and technical limitations that make it far from convenient as a diagnostic test in clinical practice. Genotypic methods based on V3 genotyping represent a more feasible alternative and progressively are replacing phenotypic assays. Even though their sensitivity to detect X4-tropic variants is lower compared to Trofile™, recent studies have demonstrated that specific genotypic tools (geno2pheno and PSSM) are comparable to Trofile™ and ES-Trofile™ in predicting virologic response to maraviroc. This review summarizes clinical and methodological recommendations for the genotypic determination of HIV tropism to guide therapeutic decisions with CCR5 antagonists in HIV therapeutics.
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Antagonistas de los Receptores CCR5 , Inhibidores de Fusión de VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , Tropismo Viral , Ciclohexanos/uso terapéutico , Genotipo , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Maraviroc , Fenotipo , Triazoles/uso terapéuticoRESUMEN
OBJECTIVE: To assess the effectiveness and safety of antiretroviral therapy with unboosted atazanavir (400 mg once daily) plus co-formulated abacavir/lamivudine as a treatment simplification strategy in HIV-infected patients with sustained viral suppression in routine clinical practice. METHODS: We performed a retrospective study including patients who were switched to unboosted atazanavir plus abacavir/lamivudine and whose HIV-1 RNA was <50 copies/mL. The primary endpoint was the percentage of subjects who maintained viral suppression after 48 weeks of follow-up. Secondary endpoints included the percentage of subjects who maintained viral suppression after 96 weeks of follow-up, the incidence of adverse events, changes in CD4+ T-cell count and in lipid profile, and the percentage of patients with subtherapeutic atazanavir trough concentrations during follow-up. RESULTS: Forty-six patients were included. None had a prior history of resistance to protease inhibitors or to lamivudine or abacavir. The percentage of patients with viral suppression at Week 48 was 73.9% when all the included patients were considered (full dataset analysis) and 85.0% when only subjects on treatment were considered. There was a continuous immune recovery and an improvement in lipid profile during follow-up. Two thirds of the patients had subtherapeutic atazanavir trough concentrations in plasma in at least one determination during follow-up. CONCLUSION: Antiretroviral therapy with unboosted atazanavir plus abacavir/lamivudine is safe and effective in the long term as a treatment simplification strategy in HIV-infected patients with sustained virological suppression in routine clinical practice.
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Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1 , Lamivudine/uso terapéutico , Oligopéptidos/uso terapéutico , Piridinas/uso terapéutico , Adulto , Terapia Antirretroviral Altamente Activa , Sulfato de Atazanavir , Recuento de Linfocito CD4 , Didesoxinucleósidos , Combinación de Medicamentos , Femenino , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/normas , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Lamivudine/normas , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Oligopéptidos/normas , Piridinas/normas , ARN Viral/sangre , Estudios Retrospectivos , Ritonavir/uso terapéutico , Carga ViralRESUMEN
OBJECTIVES: The aim of this study was to assess the influence of hepatitis B virus or hepatitis C virus co-infection and the extent of liver fibrosis on saquinavir and ritonavir pharmacokinetics in HIV-infected subjects without liver function impairment. METHODS: A cross-sectional, comparative study enrolling HIV-infected adults receiving saquinavir/ritonavir 1000/100 mg twice daily or 1500/100 mg once daily was conducted. Patients with chronic viral hepatitis (HEP+) were grouped as having advanced liver fibrosis (HEP+/FIB+) or not (HEP+/FIB-) based on the FIB-4 index. Saquinavir and ritonavir trough concentrations (C(trough)) in plasma were determined by HPLC. The geometric mean ratio (GMR) was used to compare saquinavir and ritonavir C(trough) between HEP- and HEP+ patients, and the influence of the extent of liver fibrosis on saquinavir and ritonavir pharmacokinetics was explored using analysis of variance. RESULTS: One hundred and thirty-eight patients on twice-daily saquinavir/ritonavir (67 HEP-, 71 HEP+) and 36 patients on once-daily saquinavir/ritonavir (12 HEP-, 24 HEP+) were included. Saquinavir C(trough) was comparable between HEP- and HEP+ patients receiving either saquinavir/ritonavir 1000/100 mg twice daily [GMR 0.91, 95% confidence interval (CI) 0.60-1.37; P = 0.655] or 1500/100 mg once daily (GMR 0.88, 95% CI 0.39-1.97; P = 0.752). Similarly, ritonavir C(trough) was also comparable between HEP- and HEP+ patients. The extent of liver fibrosis was not significantly related to saquinavir or ritonavir C(trough) in patients receiving either of the two studied doses. CONCLUSIONS: Saquinavir C(trough) was not increased in HIV-infected patients with chronic viral hepatitis in the absence of liver function impairment. These results confirm that no specific dose modification of saquinavir/ritonavir should be recommended in this setting.
Asunto(s)
Fármacos Anti-VIH/farmacocinética , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis Viral Humana/complicaciones , Hepatitis Viral Humana/tratamiento farmacológico , Cirrosis Hepática/patología , Saquinavir/farmacocinética , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Cromatografía Líquida de Alta Presión , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Plasma/química , Ritonavir/administración & dosificación , Ritonavir/farmacocinética , Ritonavir/uso terapéutico , Saquinavir/administración & dosificación , Saquinavir/uso terapéuticoRESUMEN
The aim of this study was to evaluate the relationship between the virological response to darunavir-based salvage antiretroviral therapy and the darunavir genotypic and virtual inhibitory quotients (gIQ and vIQ, respectively). Thirty-seven HIV-infected patients failing protease inhibitor-based antiretroviral regimens who started salvage therapy containing darunavir-ritonavir were prospectively studied. The primary outcome of the study was a viral load (VL) of <50 copies/ml at week 48. The trough concentrations of darunavir in plasma, the number of darunavir resistance mutations, the change in the 50% inhibitory concentration (IC(50)) of darunavir in the virtual phenotype, and the darunavir gIQ and vIQ were correlated with the virological outcome in regression analyses adjusted by the number of active drugs in the background regimen. The VL was <50 copies/ml in 56.8% of patients at week 48. Changes in the VL were not significantly associated with the darunavir concentration (P = 0.304), the number of darunavir resistance mutations (P = 0.695), or the change in the IC(50) (P = 0.750). However, patients with darunavir vIQs of >or=1.5 had a 12-fold greater chance of achieving a >or=1 log(10) reduction in the VL (odds ratio [OR], 12.7; 95% confidence interval [95% CI], 1.9 to 81.6; P = 0.007), and a 5-fold greater chance of achieving a VL of <50 copies/ml (OR, 5.4; 95% CI, 1.2 to 24.5; P = 0.028), at week 48 than patients with darunavir vIQs of <1.5. The positive and negative predictive values of this darunavir vIQ cutoff for achieving a VL of <50 copies/ml at week 48 were 70% and 69%, respectively. The darunavir vIQ predicts virological response to darunavir-based salvage therapy better than the darunavir trough concentration or resistance mutations alone. We suggest targeting a darunavir vIQ of 1.5 for achieving long-term viral suppression.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/uso terapéutico , Sulfonamidas/uso terapéutico , Darunavir , Farmacorresistencia Viral/genética , Genes Virales , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Mutación , Estudios Prospectivos , ARN Viral/sangre , Ritonavir/uso terapéutico , Terapia Recuperativa , Factores de TiempoAsunto(s)
Fármacos Anti-VIH/farmacología , Benzoxazinas/farmacología , Didesoxinucleósidos/farmacología , Farmacorresistencia Viral , Infecciones por VIH/virología , VIH-1/genética , Lamivudine/farmacología , Mutación , Alquinos , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa , Benzoxazinas/uso terapéutico , Ciclopropanos , Didesoxinucleósidos/uso terapéutico , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Humanos , Lamivudine/uso terapéutico , España , Especificidad de la Especie , Insuficiencia del Tratamiento , Carga ViralRESUMEN
OBJECTIVE: We evaluated the safety of CD4 cell count and plasma HIV-1 RNA (pVL)-guided treatment interruptions (GTI) and determined predictors of duration of treatment interruption. METHODS: Chronically HIV-1-infected adults with sustained CD4 cell counts > 500 cells/microl and pVL < 50 copies/ml were randomly assigned to either continue with standard antiretroviral therapy (control group, n = 101) or to interrupt therapy aimed at maintaining CD4 cell counts > 350 cells/microl and pVL < 100,000 copies/ml (GTI group, n = 100). Both groups were followed for 2 years. RESULTS: There were no AIDS-defining illnesses or deaths in either group. Compared to controls, subjects interrupting therapy reduced treatment exposure by 67%, but suffered significantly more adverse events related to the intake of medication or to therapy interruption [relative hazard, 2.71; 95% confidence interval (CI), 1.64-4.49; P < 0.001), mainly due to an excess in mononucleosis-like symptoms. While GTI subjects demonstrated improvements in the psychosocial spheres of quality of life and pain reporting, GTI had no effect on the physical aspects of quality of life. Although both groups had a similar hazard for developing CD4 cell count < 200 cells/microl; at least 10% of subjects on GTI had CD4 cell counts < 350 cells/microl at every time point. Drug resistance mutations were detected in 36% of subjects but were selected de novo only in subjects interrupting non-nucleoside reverse transcriptase inhibitor therapy. Lower CD4 cell count nadir, higher set-point pVL and prior exposure to suboptimal regimens were all independent predictors of the need to reinitiate treatment. CONCLUSIONS: Overall, GTI were not as safe as continuing therapy. Despite achieving some improvements in quality of life, GTI did not reduce the overall rate of management-related adverse events.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , VIH-1/aislamiento & purificación , Adulto , Anciano , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Terapia Antirretroviral Altamente Activa/métodos , Recuento de Linfocito CD4 , Enfermedad Crónica , Progresión de la Enfermedad , Esquema de Medicación , Métodos Epidemiológicos , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Calidad de Vida , ARN Viral/sangre , Carga ViralRESUMEN
BACKGROUND: The NEFA Study was a randomized study comparing nevirapine (NVP), efavirenz (EFV) or abacavir (ABC) as substitutes for protease inhibitors in a large group of HIV-1-infected patients successfully treated with antiretroviral regimens containing protease inhibitors. OBJECTIVE: To evaluate genotype and phenotype resistance patterns among patients who have experienced virological failure under one of the three study arms. METHODS: Patients with virological failure, defined as two consecutive determinations of HIV-1 RNA > 200 copies/ml, were analysed for phenotypic susceptibility and HIV-1 mutations. RESULTS: Of the 460 patients included in the study, 51 (11%) experienced virological failure after 24 months of follow-up while on assigned study medication. A higher proportion of patients in the ABC [25 (17%)] than in the NVP [14 (9%)] or EFV [12 (8%)] arms selected resistance to the study drug (P = 0.04). Moreover, a much higher number of resistance mutations to one or more of the backbone nucleoside reverse transcriptase inhibitor drugs contained in the failing regimen were observed in the ABC than in the EFV or NVP arms. In general, there was a good concordance among genotype and phenotype resistance testing, except for ABC, stavudine and didanosine, where phenotypic resistance testing added valuable information (fold change in the median inhibitory concentration). CONCLUSIONS: Cross-resistance involving nucleoside reverse transcriptase inhibitor drugs might explain the higher risk of virological failure in patients switched to ABC-containing antiretroviral therapy. Phenotypic resistance testing may be helpful in interpreting unclear genotypic results.