Impacto y características de la gripe nosocomial a lo largo de 10 temporadas en un hospital universitario de tercer nivel / Impact and characteristics of hospital-acquired influenza over 10 seasons in a third-level university hospital

Objetivos: Analizar las características de los pacientes con gripe nosocomial, compararlas con las de los enfermos con diagnóstico de gripe comunitaria para estudiar posibles diferencias e identificar posibles factores de riesgo asociados a este tipo de gripe. Pacientes y métodos: Estudio observacional, transversal y retrospectivo de los pacientes hospitalizados con diagnóstico microbiológico de gripe en un hospital universitario de tercer nivel durante 10 temporadas, de 2009 a 2019. Se definió como gripe nosocomial aquella infección cuyos síntomas comenzaron 72 h después del ingreso hospitalario y se analizó su incidencia, características y consecuencias. Resultados: Se incluyó a un total de 1.260 pacientes hospitalizados con diagnóstico microbiológico de gripe, de los cuales 110 (8,7%) fueron nosocomiales. Los pacientes con gripe adquirida en el hospital eran más jóvenes (71,74±16,03 años; p=0,044), tuvieron una estancia hospitalaria mayor (24,25±20,25 días; p<0,001), tenían con mayor frecuencia antecedentes de enfermedades pulmonares crónicas (p=0,010), inmunodeficiencias (p<0,001) y se asociaron con mayor desarrollo de sobreinfección bacteriana (p<0,001), distrés respiratorio (p=0,003) e ingreso en la unidad de cuidados intensivos (UCI) (p<0,001). En el análisis por regresión logística multivariante se identificaron como factores de riesgo independientes: inmunodeficiencia (ORa=2,33; IC 95%: 1,47-3,60); ingreso en UCI (ORa=4,29; IC 95%: 2,23-10,91); desarrollo de sobreinfección bacteriana (ORa=1,64; IC 95%: 1,06-2,53) y de distrés respiratorio (ORa=3,88; IC 95%: 1,23-12,23).Conclusiones: La gripe nosocomial es más frecuente en los pacientes con antecedentes de inmunodeficiencia. Además, los enfermos con gripe hospitalaria tienen un riesgo aumentado de sobreinfección bacteriana, ingreso en UCI y desarrollo de distrés respiratorio.(AU)

Objectives: To analyze the characteristics of patients with nosocomial flu, to compare them with patients with community-acquired influenza to study possible differences and to identify possible risk factors associated with this type of flu. Patients and methodsObservational, cross-sectional and retrospective study of hospitalized patients with a microbiological confirmation of influenza in a third-level university hospital over 10seasons, from 2009 to 2019. Nosocomial influenza was defined as that infection whose symptoms began 72h after hospital admission, and its incidence, characteristics and consequences were further analyzed. Results: A total of 1260 hospitalized patients with a microbiological diagnosis of influenza were included, which 110 (8.7%) were nosocomial. Patients with hospital-acquired influenza were younger (71.74±16.03 years, P=0.044), had a longer hospital stay (24.25±20.25 days, P<0.001), had more frequently a history of chronic pulmonary pathologies (P=0.010), immunodeficiency (P<0.001), and were associated with greater development of bacterial superinfection (P<0.001), respiratory distress (P=0.003), and admission to the intensive care unit (ICU) (P<0.001). In the multivariate logistic regression analysis, the following characteristics were identified as independent risk factors: immunodeficiency (ORa=2.33; 95% CI: 1.47-3.60); ICU admission (ORa=4.29; 95% CI: 2.23-10.91); bacterial superinfection (ORa=1.64; 95% CI: 1.06-2.53) and respiratory distress (ORa=3.88; 95% CI: 1.23-12.23). Conclusions: Nosocomial influenza is more common in patients with a history of immunodeficiency. In addition, patients with hospital-acquired influenza had an increased risk of bacterial superinfection, admission to the ICU, and development of respiratory distress.(AU)

Impact and characteristics of hospital-acquired influenza over 10 seasons in a third-level university hospital.

OBJECTIVES: To analyze the characteristics of patients with nosocomial flu, to compare them with patients with community-acquired influenza to study possible differences and to identify possible risk factors associated with this type of flu. PATIENTS AND METHODS: Observational, cross-sectional and retrospective study of hospitalized patients with a microbiological confirmation of influenza in a third-level university hospital over 10 seasons, from 2009 to 2019. Nosocomial influenza was defined as that infection whose symptoms began 72h after hospital admission, and its incidence, characteristics and consequences were further analyzed. RESULTS: A total of 1260 hospitalized patients with a microbiological diagnosis of influenza were included, which 110 (8.7%) were nosocomial. Patients with hospital-acquired influenza were younger (71.74±16.03 years, P=0.044), had a longer hospital stay (24.25±20.25 days, P<0.001), had more frequently a history of chronic pulmonary pathologies (P=0.010), immunodeficiency (P<0.001), and were associated with greater development of bacterial superinfection (P<0.001), respiratory distress (P=0.003), and admission to the intensive care unit (ICU) (P<0.001). In the multivariate logistic regression analysis, the following characteristics were identified as independent risk factors: immunodeficiency (ORa=2.33; 95% CI: 1.47-3.60); ICU admission (ORa=4.29; 95% CI: 2.23-10.91); bacterial superinfection (ORa=1.64; 95% CI: 1.06-2.53) and respiratory distress (ORa=3.88; 95% CI: 1.23-12.23). CONCLUSIONS: Nosocomial influenza is more common in patients with a history of immunodeficiency. In addition, patients with hospital-acquired influenza had an increased risk of bacterial superinfection, admission to the ICU, and development of respiratory distress.

Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial.

Importance: Remdesivir demonstrated clinical benefit in a placebo-controlled trial in patients with severe coronavirus disease 2019 (COVID-19), but its effect in patients with moderate disease is unknown. Objective: To determine the efficacy of 5 or 10 days of remdesivir treatment compared with standard care on clinical status on day 11 after initiation of treatment. Design, Setting, and Participants: Randomized, open-label trial of hospitalized patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moderate COVID-19 pneumonia (pulmonary infiltrates and room-air oxygen saturation >94%) enrolled from March 15 through April 18, 2020, at 105 hospitals in the United States, Europe, and Asia. The date of final follow-up was May 20, 2020. Interventions: Patients were randomized in a 1:1:1 ratio to receive a 10-day course of remdesivir (n = 197), a 5-day course of remdesivir (n = 199), or standard care (n = 200). Remdesivir was dosed intravenously at 200 mg on day 1 followed by 100 mg/d. Main Outcomes and Measures: The primary end point was clinical status on day 11 on a 7-point ordinal scale ranging from death (category 1) to discharged (category 7). Differences between remdesivir treatment groups and standard care were calculated using proportional odds models and expressed as odds ratios. An odds ratio greater than 1 indicates difference in clinical status distribution toward category 7 for the remdesivir group vs the standard care group. Results: Among 596 patients who were randomized, 584 began the study and received remdesivir or continued standard care (median age, 57 [interquartile range, 46-66] years; 227 [39%] women; 56% had cardiovascular disease, 42% hypertension, and 40% diabetes), and 533 (91%) completed the trial. Median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group. On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; 95% CI, 1.09-2.48; P = .02). The clinical status distribution on day 11 between the 10-day remdesivir and standard care groups was not significantly different (P = .18 by Wilcoxon rank sum test). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care. Conclusions and Relevance: Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment. Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT04292730.

Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with lopinavir/ritonavir plus lamivudine for initial ART in HIV infected adults / Análisis de coste/eficacia de las pautas preferentes de GESIDA/Plan Nacional sobre el Sida y de biterapia con lopinavir/ritonavir más lamivudina para el tratamiento antirretroviral inicial en adultos infectados por el virus de la inmunodeficiencia humana

INTRODUCTION: The National AIDS Plan and the Spanish AIDS study group (GESIDA) proposes 'preferred regimens' (PR) of antiretroviral treatment (ART) as initial therapy in HIV-infected patients. In 2013, the recommended regimens were all triple therapy regimens. The Gardel Study assessed the efficacy of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) plus lamivudine (3TC). Our objective is to evaluate the GESIDA PR and the DT regimen LPV/r+3TC cost/efficacy ratios. METHODS: Decision tree models were built. Efficacy: probability of having viral load < 50 copies/mL at week 48. ART regime cost: costs of ART, adverse effects, and drug resistance tests during the first 48 weeks. RESULTS: Cost/efficacy ratios varied between 5,817€ and 13,930 € per responder at 48 weeks, for the DT of LPV/r+3TC and tenofovir DF/emtricitabine+raltegravir, respectively. CONCLUSIONS: Taking into account the official Spanish prices of ART, the most efficient regimen was DT of LPV/r+3TC, followed by the triple therapy with non-nucleoside containing regimens

INTRODUCCIÓN: El Plan Nacional sobre el Sida y el grupo de estudio del SIDA-SEIMC (GESIDA) propone «regímenes preferentes» (RP) de tratamiento antirretroviral (TAR) como terapia inicial en pacientes infectados por VIH. Todos los regímenes recomendados en el año 2013 eran de terapia triple. El Estudio Gardel evaluó la eficacia de una doble terapia (DT) que combina lopinavir/ritonavir (LPV/r) más lamivudina (3TC). Nuestro objetivo es evaluar los ratios de coste/eficacia de los RP de GESIDA y el régimen de DT LPV/r+3TC. MÉTODOS: Construcción de árboles de decisión como modelos de evaluación económica. Eficacia: probabilidad de tener una carga viral <50 copias/ml en la semana 48. Coste del régimen de TAR: coste del TAR, efectos adversos y tests de resistencia durante las primeras 48 semanas. RESULTADOS: Los ratios de coste/eficacia variaron entre 5.817€ y 13.930€ por respondedor a las 48 semanas, para la DT LPV/r+3TC y tenofovir DF/emtricitabina+raltegravir, respectivamente. CONCLUSIONES: Con los precios oficiales españoles de TAR, el régimen más eficiente fue la DT con LPV/r+3TC, seguida de la terapia triple con regímenes que no contienen nucleósidos

Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with lopinavir/ritonavir plus lamivudine for initial ART in HIV infected adults.

INTRODUCTION: The National AIDS Plan and the Spanish AIDS study group (GESIDA) proposes "preferred regimens" (PR) of antiretroviral treatment (ART) as initial therapy in HIV-infected patients. In 2013, the recommended regimens were all triple therapy regimens. The Gardel Study assessed the efficacy of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) plus lamivudine (3TC). Our objective is to evaluate the GESIDA PR and the DT regimen LPV/r+3TC cost/efficacy ratios. METHODS: Decision tree models were built. EFFICACY: probability of having viral load <50 copies/mL at week 48. ART regime cost: costs of ART, adverse effects, and drug resistance tests during the first 48 weeks. RESULTS: Cost/efficacy ratios varied between 5,817 and 13,930 euros per responder at 48 weeks, for the DT of LPV/r+3TC and tenofovir DF/emtricitabine+raltegravir, respectively. CONCLUSIONS: Taking into account the official Spanish prices of ART, the most efficient regimen was DT of LPV/r+3TC, followed by the triple therapy with non-nucleoside containing regimens.

[Consensus statement on the clinical management of human immunodeficiency virus-associated neurocognitive disorders]. / Documento de consenso sobre el manejo clínico de los trastornos neurocognitivos asociados a la infección por el virus de la inmunodeficiencia humana (enero 2013).

OBJECTIVE: To develop a consensus document containing clinical recommendations for the management of human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND). METHODS: We assembled a panel of experts appointed by GeSIDA and the Secretariat of the National AIDS Plan (PNS), including internal medicine physicians with expertise in the field of HIV, neuropsychologists, neurologists and neuroradiologists. Scientific information was reviewed to October 2012 in publications and conference papers. In support of the recommendations using two levels of evidence: the strength of the recommendation in the opinion of the experts (A, B, C) and the level of empirical evidence (I, II, III), two levels based on the criteria of the Infectious Disease Society of America, already used in previous documents GeSIDA/SPNS. RESULTS: Multiple recommendations for the clinical management of these disorders are provided, including two graphics algorithms, considering both the diagnostic and possible therapeutic strategies. CONCLUSIONS: Neurocognitive disorders associated with HIV infection is currently highly prevalent, are associated with a decreased quality of life and daily activities, and given the possibility of occurrence of an increase in the coming years, there is a need to adequately manage these disorders, from a diagnostic as well as therapeutic point of view, and always from a multidisciplinary perspective.

Controversias y futuro del abordaje de la enfermedad cardiovascular en pacientes con VIH / Controversies and future of the approach to cardiovascular disease in HIV patients

Las enfermedades cardiovasculares son un problema creciente en pacientes infectados por el virus de inmunodeficiencia humana (VIH). El aumento del riesgo cardiovascular en población infectada tiene un ori gen multifactorial. En el momento actual, no se puede concluir qué elemento tiene más peso en esta ecuación, si los factores de riesgo clásicos, el propio virus o el tratamiento antirretroviral. El riesgo absoluto de enfermedad cardiovascular de cada paciente dependerá de su perfi l de riesgo global. En la actualidad no hay datos que obliguen a evaluar de forma diferente al paciente con VIH a la hora de manejar los factores de riesgo cardiovascular. Se debería incorporar a la rutina clínica diaria la evaluación cuidadosa de los factores de riesgo y el cálculo del riesgo cardiovascular mediante la aplicación de ecuaciones de riesgo

Cardiovascular diseases are an increasing problem in patients with HIV infection. The causes of the increased cardiovascular risk in HIV-infected patients are multifactorial. Currently, the question of which factor has the most weight in this equation - whether traditional risk factors, the virus per se or antiretroviral therapy - remains to be determined. The absolute risk of cardiovascular disease in a particular patient depends on the composite risk profile. At present, there are no data to support a distinct approach to cardiovascular risk evaluation in HIV-infected patients. Cardiovascular risk equations should be incorporated into routine daily clinical assessment in order to identify patients in need of specific interventions

[Controversies and future of the approach to cardiovascular disease in HIV patients]. / Controversias y futuro del abordaje de la enfermedad cardiovascular en pacientes con VIH.

Cardiovascular diseases are an increasing problem in patients with HIV infection. The causes of the increased cardiovascular risk in HIV-infected patients are multifactorial. Currently, the question of which factor has the most weight in this equation - whether traditional risk factors, the virus per se or antiretroviral therapy - remains to be determined. The absolute risk of cardiovascular disease in a particular patient depends on the composite risk profile. At present, there are no data to support a distinct approach to cardiovascular risk evaluation in HIV-infected patients. Cardiovascular risk equations should be incorporated into routine daily clinical assessment in order to identify patients in need of specific interventions.

[Prospective validation of a pharmacogenetic test: the PREDICT-1 study]. / Validación prospectiva de un test farmacogenético: estudio PREDICT-1.

The aim of the PREDICT-1 study was to determine the clinical utility of the pharmacogenetic test identifying HLA-B*5701 to reduce the incidence of hypersensitivity reaction to abacavir, diagnosed clinically and with immunological confirmation, as well as to reduce unwarranted withdrawal of this drug. In the PREDICT-1 study, 1,956 patients were randomized to be screened for HLA-B*5701 before starting abacavir treatment (excluding participants who were HLA-B*5701-positive) or to receive abacavir without knowing their HLA-B*5701 status under conventional clinical monitoring. The prevalence of HLA-B*5701-positivity was 5.7%. In the group that underwent prospective screening, no hypersensitivity tests with immunological confirmation (by positive epicutaneous patch testing) were observed compared with an incidence of 2.7% in the group undergoing standard follow-up. The sensitivity of prospective screening in predicting immunologically confirmed hypersensitivity reaction to abacavir was 100% and its negative predictive value was 100%. The number of clinically suspected hypersensitivity reactions to abacavir was also lower in the screened group (3.4% versus 7.8% in the group undergoing conventional follow-up). The sensitivity of epicutaneous patch testing for immunological confirmation was 100%.

Datos clínicos I. Experiencia clínica de tenofoviren combinaciones con inhibidores no análogos de la transcriptasa inversa / Clinical data I. Clinical experience with tenofovir in combination with nonnucleoside analogue transcriptase inhibitors

La aparición del tratamiento antirretroviral de granactividad ha supuesto una drástica mejora en elpronóstico de los pacientes infectados por el virus deinmunodeficiencia humana. La gran eficacia de lostratamientos antirretrovirales ha desplazado el interéshacia nuevos aspectos de la terapéutica, como ladosificación 1 vez al día de los antirretrovirales, el uso ydiseño de nuevas combinaciones de dosis fijas defármaco y el perfil de seguridad de los fármacos. Eltenofovir disoproxil fumarato (TDF) es un análogo denucleótido inhibidor de la transcriptasa inversa que seadministra 1 vez al día y que en combinación es uno delos fármacos recomendados en pautas de inicio por lamayoría de las guías de práctica clínica. En la actualidad,se dispone de una experiencia de más de 5 años queconfirma que el TDF en combinación con los inhibidoresno análogos de la transcriptasa inversa es un fármacocómodo, seguro, altamente eficaz y adecuado pararegímenes una vez al día con escaso número de comprimidos(AU)

Highly active antirretroviral therapy has transformed theprognosis of patient infected with humanimmunodeficiency virus. The efficacy of these drugs hasshifted the clinicians` attention to other therapeuticaspects like QD regimens, fixed dose combinations andclinical safety. Tenofovir disoproxil fumarate(TDF) is anucleoside monophosphate (nucleotide) analogue that inhibits reverse trascriptase enzyme. It’s administered ina q.d. regimen and it’s recommended by most of theclinical guidelines as a start regimen in combination withtwo other drugs. Currently more than 5 years of clinicalexperience is accumulated and confirmed that acombination of tenofovir and a nonnucleoside analoguetranscriptase inhibitor is a comfortable, safe, highlyeffective and low pill burden regimen(AU)

Datos clínicos I. Experiencia clínica de tenofovir en combinaciones con inhibidores no análogos de la transcriptasa inversa / Clinical data I. Clinical experience with tenofovir in combination with nonnucleoside analogue transcriptase inhibitors

La aparición del tratamiento antirretroviral de gran actividad ha supuesto una drástica mejora en el pronóstico de los pacientes infectados por el virus de inmunodeficiencia humana. La gran eficacia de los tratamientos antirretrovirales ha desplazado el interés hacia nuevos aspectos de la terapéutica, como la dosificación 1 vez al día de los antirretrovirales, el uso y diseño de nuevas combinaciones de dosis fijas de fármaco y el perfil de seguridad de los fármacos. El tenofovir disoproxil fumarato (TDF) es un análogo de nucleótido inhibidor de la transcriptasa inversa que se administra 1 vez al día y que en combinación es uno de los fármacos recomendados en pautas de inicio por la mayoría de las guías de práctica clínica. En la actualidad, se dispone de una experiencia de más de 5 años que confirma que el TDF en combinación con los inhibidores no análogos de la transcriptasa inversa es un fármaco cómodo, seguro, altamente eficaz y adecuado para regímenes una vez al día con escaso número de comprimidos

Highly active antirretroviral therapy has transformed the prognosis of patient infected with human immunodeficiency virus. The efficacy of these drugs has shifted the clinicians` attention to other therapeutic aspects like QD regimens, fixed dose combinations and clinical safety. Tenofovir disoproxil fumarate(TDF) is a nucleoside monophosphate (nucleotide) analogue that inhibits reverse trascriptase enzyme. It¿s administered in a q.d. regimen and it¿s recommended by most of the clinical guidelines as a start regimen in combination with two other drugs. Currently more than 5 years of clinical experience is accumulated and confirmed that a combination of tenofovir and a nonnucleoside analogue transcriptase inhibitor is a comfortable, safe, highly effective and low pill burden regimen

Validación prospectiva de un test farmacogenético: estudio PREDICT-1 / Prospective validation of a pharmacogenetic test: the PREDICT-1 study

El ensayo PREDICT-1 tuvo como objetivo comprobar la utilidad clínica del test farmacogenético que determina el HLA-B*5701 para reducir la incidencia de reacción de hipersensibilidad (RHS) a abacavir (ABC) diagnosticada clínicamente y con confirmación inmunológica, así como para reducir el abandono injustificado de este fármaco. En el estudio PREDICT-1 se aleatorizó a 1.956 pacientes a ser sometidos a cribado de HLA-B*5701 previo a la instauración de tratamiento con ABC (excluyendo a los sujetos positivos), o bien a recibir ABC con el desconocimiento de su HLA-B*5701 bajo vigilancia clínica convencional. La prevalencia de positividad para HLA-B*5701 fue del 5,7%. En el grupo en que se realizó el cribado prospectivo no se observó ningún caso de RHS a ABC confirmada inmunológicamente (con test epicutáneo positivo) frente a una incidencia de 2,7% en el grupo con vigilancia estándar. La sensibilidad del cribado prospectivo para predecir la RHS a ABC confirmada inmunológicamente fue 100% y su valor predictivo negativo también fue del 100%. La RHS a ABC sospechada clínicamente también fue inferior en el grupo sometido a cribado; 3,4 frente a 7,8% en el grupo de seguimiento convencional. La realización del test epicutáneo como prueba de confirmación inmunológica demostró una sensibilidad del 100%(AU)

The aim of the PREDICT-1 study was to determine the clinical utility of the pharmacogenetic test identifying HLAB* 5701 to reduce the incidence of hypersensitivity reaction to abacavir, diagnosed clinically and with immunological confirmation, as well as to reduce unwarranted withdrawal of this drug. In the PREDICT-1 study, 1,956 patients were randomized to be screened for HLA-B*5701 before starting abacavir treatment (excluding participants who were HLA-B*5701-positive) or to receive abacavir without knowing their HLA-B*5701 status under conventional clinical monitoring. The prevalence of HLAB* 5701-positivity was 5.7%. In the group that underwent prospective screening, no hypersensitivity tests with immunological confirmation (by positive epicutaneous patch testing) were observed compared with an incidence of 2.7% in the group undergoing standard follow-up. The sensitivity of prospective screening in predicting immunologically confirmed hypersensitivity reaction to abacavir was 100% and its negative predictive value was 100%. The number of clinically suspected hypersensitivity reactions to abacavir was also lower in the screened group (3.4% versus 7.8% in the group undergoing conventional follow-up). The sensitivity of epicutaneous patch testing for immunological confirmation was 100%(AU)

Tenofovir disoproxil fumarate-emtricitabine coformulation for once-daily dual NRTI backbone.

Truvada is the coformulation of tenofovir disoproxil fumarate (TDF; 300 mg) and emtricitabine (FTC; 200 mg) in a single tablet, providing the nucleotide backbone for once-daily dosing, as a component of highly active antiretroviral therapy (HAART). TDF (the bioavailable prodrug of tenofovir) is hydrolyzed to tenofovir intracellularly and phosphorylated to the active metabolite, tenofovir diphosphate. Tenofovir is a nucleotide analog of deoxyadenosine monophosphate, with activity against HIV-1, -2 and hepatitis B virus. FTC, the fluorinated derivative of lamivudine, is an analog of deoxycitidine, active against HIV-1, -2 and hepatitis B virus. Their long half-lives in plasma and in peripheral blood mononuclear cells allow once-daily dosing. Both are eliminated renally. Resistance mutation K65R is selected for by tenofovir and confers a two- to fourfold reduced susceptibility to this drug. The incidence of K65R is low (3%) and has not been observed in clinical trials with the concomitant use of tenofovir and FTC. FTC selects for M184V mutation less frequently than lamivudine. Tenofovir drug interactions include increased exposure to didanosine and inferior immune recovery that preclude their concomitant use. Boosted protease inhibitors increase exposure to tenofovir without dose adjustment required. FTC has no significant drug interactions. They are not metabolized by cytochrome P450, which confers little potential for interactions with drugs metabolized by these enzymes. As tenofovir and FTC are renally eliminated, drugs eliminated by tubular secretion must be avoided. Both antiretrovirals, as individual agents and in coadministration have evidenced antiviral potency in clinical trials. Pivotal study 934 evidenced superior efficacy of the combination TDF/FTC/efavirenz (EFV) versus zidovudine/FTC/EFV. The toxicity profile of tenofovir and FTC has been extensively studied. Lipid profile is more favorable with tenofovir than thymidine analog. Tenofovir requires surveillance of glomerular filtration rate and dosing interval adjustment when creatinine clearance is less than 50 ml/min and avoidance less than 30 ml/min. Fat loss is less likely with tenofovir than with thymidine analog. Clinical trials have assessed the performance of the coformulation of TDF and FTC.

[Retrospective epidemiological study on the durability of the treatment of HIV infection or AIDS in Spain]. / Estudio epidemiológico retrospectivo sobre la duración del tratamiento de la infección por el virus de la inmunodeficiencia humana en España.

BACKGROUND AND OBJECTIVE: To know the durability of consecutive regimens of antiretroviral treatment is important to design a long-term therapy, but there is not much information about this subject. PATIENTS AND METHOD: Retrospective epidemiological study of a sample of 401 patients who began antiretroviral treatment between January 1997 and April 2000 at ten Spanish hospitals. The duration of each consecutive antiretroviral regimen was calculated and the reasons for modification and discontinuation were described. RESULTS: In the 3 years and 3 months covered by the study, 48.6% of the patients received more than one regimen of therapy. Seventy five of the initial prescribed combinations included protease inhibitors. Median duration of consecutive lines of therapy was decreasing: 560, 360, 330 and 202 days for the first, second, third and fourth regimens, respectively. The main reason to modification was intolerance or toxicity (46.2, 49.1 and 47.1% for the first, second and third modification). A fifth of changes was originated by difficulties to follow the therapy. Virological failure was the reason for modification in 21.8, 24.5 and 26.5% of first, second and third changes. CONCLUSIONS: Duration of consecutive antiretroviral regimens progressively decreases. Intolerance or drug toxicity were the main reasons conditioning the change of treatment.