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BACKGROUND: Incidence of anal cancer (AC) caused by persistent human papillomavirus (HPV) infection has risen in the last years in men who have sex with men (MSM) living with HIV. There is consensus that this population should be screened for anal precancerous lesions, but the role of HPV DNA testing in AC screening programmes is still under debate. OBJECTIVES: This study employed two molecular test to detect anal HPV DNA and compared assay performance and prognostic value for the diagnosis of histology proven high-grade intraepithelial anal lesions. METHODS: MSM living with HIV attended their regular check-up visits consisting of detection of anal HPV infection, anal cytology, digital anorectal examination and high resolution anoscopy. HPV DNA was detected using Hybrid Capture 2 High-Risk test (HC2, total assay) and LINEAR ARRAY HPV Genotyping Test (LA, type-specific assay) RESULTS: Among 274 participant, prevalence of HPV DNA was 48.5% by HC2 and 89.4% by LA. HPV16 (30.6%) and HPV6 (19.6%) were the most common genotypes identified. Prevalence of multiple HPV infections was 56.2%. Agreement between HPV DNA assays was 75.2% (κ=0.51; 95% CI 0.42 to 0.60). Total HPV detection demonstrated high sensitivity (90%; 95% CI 68.3 to 98.8) and moderate specificity (58.4%; 95% CI 50.2 to 66.3), while type-specific HPV16/18 genotyping provided an increase in specificity and showed the highest area under the curve (0.81; 95% CI 0.74 to 0.89) and Youden's index (0.63). CONCLUSIONS: Both methodologies identified a high prevalence of anal HPV infection and multiple HPV infections in MSM living with HIV, showing a moderate overall agreement between them. Either total HPV detection or type-specific HPV16/18 detection together with a threshold ≥atypical squamous cells of undetermined significance for abnormal cytology showed an acceptable diagnostic accuracy.
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Neoplasias del Ano , Infecciones por VIH , Infecciones por Papillomavirus , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/epidemiología , Virus del Papiloma Humano , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Canal Anal , Neoplasias del Ano/diagnóstico , Neoplasias del Ano/epidemiología , Neoplasias del Ano/patología , Papillomaviridae/genética , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , PrevalenciaRESUMEN
PURPOSE: We aimed to describe the distribution of gestational age at birth (GAB) to inform the estimation of GAB when clinical or obstetric estimates are not available for perinatal pharmacoepidemiology studies. METHODS: We estimated GAB (median, mode, mean, and standard deviation) and percentage born at each gestational week in groups based on plurality and other variables for live births in CDC's U.S. birth data. RESULTS: In 2020, 3 617 213 newborns had birth certificates with nonmissing GAB. Among singletons (3 501 693), median and mode GAB were both 39 weeks. Births with lower median GAB were from women with eclampsia (37 weeks) or receiving intensive care (37 weeks); newborns receiving intensive care (37 weeks); newborns with birth weight <2500 g (35 weeks), <1500 g (28 weeks), or <1000 g (25 weeks); and newborns not discharged alive (23 weeks). Among twins (112 633), median GAB was 36 weeks (mode, 37 weeks). Additional noteworthy groups were women with 0-6 prenatal visits (median, 34 weeks) or 7-8 prenatal visits (median, 35 weeks) or aged 15-19 years (median, 35 weeks). CONCLUSIONS: Some maternal and infant groups had distinct GAB distributions in the United States. This information can be useful in estimating GAB when individual-level clinical estimates are not available, such as in database studies of medication use during pregnancy.
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Resultado del Embarazo , Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Lactante , Estados Unidos/epidemiología , Humanos , Masculino , Recien Nacido Prematuro , Recién Nacido de Bajo Peso , Edad Gestacional , Certificado de Nacimiento , Vigilancia de la Población , Técnicas Reproductivas AsistidasRESUMEN
Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.
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Antineoplásicos , COVID-19 , Anticuerpos Monoclonales , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/diagnóstico , COVID-19/prevención & control , Vacunas contra la COVID-19 , Detección Precoz del Cáncer , Humanos , SARS-CoV-2 , VacunaciónRESUMEN
This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3-6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 109 /ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16-0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27-0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15-0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02-0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02-0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.
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Anticuerpos Antivirales/inmunología , Vacunas contra la COVID-19/uso terapéutico , COVID-19/prevención & control , Trasplante de Células Madre Hematopoyéticas , SARS-CoV-2/inmunología , Adolescente , Adulto , Anciano , COVID-19/epidemiología , COVID-19/inmunología , Femenino , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Estudios Prospectivos , España/epidemiología , Adulto JovenRESUMEN
PURPOSE: Publications provide important information for clinicians, researchers, and patients. Key methodological elements must be reported for maximum transparency. We identified key methodological elements necessary for fully understanding perinatal pharmacoepidemiology research and quantified the proportion of studies that reported these elements in a sample of publications. METHODS: Key methodological elements were identified from guidelines from regulatory agencies, literature, and subject-matter knowledge: source of information to determine pregnancy start; mother- or father-infant linkages (process, success rate); unit of analysis; and whether non-live births and fetuses with various anomalies were included in the study population. We conducted a literature review for recent observational studies on medical product utilization or safety during pregnancy and estimated the prevalence of reporting these elements. RESULTS: Data were extracted from a random sample of 100 publications; 8% were published in epidemiology/pharmacoepidemiology journals; 85% were medical product-safety studies. Of publications for which each element was applicable, 43% reported the source for determining pregnancy start; 57%, whether the study population included multifetal pregnancies; 39%, whether it included more than one pregnancy per woman; 27%, whether it included fetuses with chromosomal abnormalities; 60%, fetuses with major congenital malformations; and 93%, non-live births. Of the 20 studies with mother-infant linkage, 35% described the process; 21% reported the linkage success rate. Among studies with more than one pregnancy/offspring per woman, 22% reported methods addressing sibling correlation. CONCLUSIONS: In this sample of pregnancy-related pharmacoepidemiology publications, completeness of reporting could have been improved. A pregnancy-specific checklist would increase transparency in the dissemination of study results.
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Lista de Verificación , Farmacoepidemiología , Femenino , Humanos , Embarazo , Proyectos de InvestigaciónRESUMEN
BACKGROUND: Predictive factors of significant functional tricuspid regurgitation (FTR) are not completely understood. We investigated sex-related differences in predictors of FTR progression. METHOD: Clinical and echocardiographic variables were recorded in a prospective single-centre observational cohort of 251 consecutive stable patients with FTR. Multivariable logistic regression analyses stratified by sex were performed to identify predictors of significant FTR. RESULTS: The mean age of the whole cohort was 72.2±11.4 years, and 133 (53%) patients were women. Females tended to have a higher prevalence of significant FTR (22.6% vs 13.6%; p=0.066). Women were also older than men (mean age 74.4 vs 69.6 years; p<0.001), with more frequent history of arterial hypertension, worse New York Heart Association functional class, higher E/e' quotient, and higher left ventricular ejection fraction. The independent predictors of significant FTR in women were atrial fibrillation (AF) (odds ratio [OR] 10.8, 95% confidence interval [CI] 2.9-40.7; p<0.001), indexed tricuspid diameter annulus (OR 1.24, 95% CI 1.04-1.47; p=0.017), and pulmonary artery systolic pressure (PASP) (OR 1.09, 95% CI 1.04-1.15; p=0.001). The independent predictors of outcome in men were indexed tricuspid tenting height (OR 2.71, 95% CI 1.20-6.11; p=0.016), indexed tricuspid diameter annulus (OR 1.98, 95% CI 1.26-3.09; p=0.003), and PASP (OR 1.08, 95% CI 1.01-1.16; p=0.021). CONCLUSIONS: The presence of AF and longer indexed tenting height convey a greater risk of significant FTR in females and males, respectively. These findings suggest the existence of different physiopathological mechanisms involved in the progression of FTR in both sexes.
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Volumen Sistólico/fisiología , Insuficiencia de la Válvula Tricúspide/fisiopatología , Función Ventricular Izquierda/fisiología , Anciano , Ecocardiografía/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Factores Sexuales , Insuficiencia de la Válvula Tricúspide/diagnósticoRESUMEN
BACKGROUND: Left ventricular ejection fraction (LVEF) trajectories and functional recovery with current heart failure (HF) management is increasingly recognized. Type 2 diabetes mellitus (T2D) leads to a worse prognosis in HF patients. However, it is unknown whether T2D interferes with LVEF trajectories. The aim of this study was to prospectively assess very long-term (up to 15 years) LVEF trajectories in patients with and without T2D and underlying HF. METHODS: Ambulatory patients admitted to a multidisciplinary HF clinic were prospectively evaluated by scheduled two-dimensional echocardiography at baseline, 1 year, and then every 2 years afterwards, up to 15 years. Statistical analyses of LVEF change with time were performed using the linear mixed effects (LME) models, and locally weighted error sum of squares (Loess) curves were plotted. RESULTS: Of the 1921 patients, 461 diabetic and 699 non-diabetic patients with LVEF < 50% were included in the study. The mean number of echocardiography measurements performed in diabetic patients was 3.3 ± 1.6. Early LVEF recovery was similar in diabetic and non-diabetic patients, but Loess curves showed a more pronounced inverted U shape in diabetics with a more pronounced decline after 9 years. LME analysis showed a statistical interaction between T2D and LVEF trajectory over time (p = 0.009), which was statistically significant in patients with ischemic etiologies (p < 0.001). Other variables that showed an interaction between LVEF trajectories and T2D were male sex (p = 0.04) and HF duration (p = 0.008). CONCLUSIONS: LVEF trajectories in T2D patients with depressed systolic function showed a pronounced inverted U shape with a marked decline after 9 years. Diabetic cardiomyopathy may underlie the functional decline observed.
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Diabetes Mellitus Tipo 2/complicaciones , Cardiomiopatías Diabéticas/etiología , Insuficiencia Cardíaca/etiología , Volumen Sistólico , Disfunción Ventricular Izquierda/etiología , Función Ventricular Izquierda , Anciano , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/terapia , Cardiomiopatías Diabéticas/diagnóstico por imagen , Cardiomiopatías Diabéticas/fisiopatología , Cardiomiopatías Diabéticas/terapia , Progresión de la Enfermedad , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/terapiaRESUMEN
Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/µl compared with 500 cells/µl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.
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Fármacos Anti-VIH/administración & dosificación , Monitoreo de Drogas/estadística & datos numéricos , Infecciones por VIH/tratamiento farmacológico , Adulto , Recuento de Linfocito CD4 , Toma de Decisiones , Femenino , Infecciones por VIH/mortalidad , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/análisis , Proyectos de Investigación , Análisis de Supervivencia , Carga ViralRESUMEN
PURPOSE: This drug utilization study of ivabradine evaluated prescriber compliance with the new risk minimization measures (RMMs), communicated starting 2014 following preliminary results from the SIGNIFY study. METHODS: This was a multinational (five European countries) chart review study with two study periods: pre-RMM and post-RMM. Patients initiating ivabradine for chronic stable angina pectoris in routine clinical practice were identified across general practitioners and specialists. The primary outcome analysis evaluated the compliance with the new RMMs, ie, use in patients with a heart rate greater than or equal to 70 bpm at initiation, no doses higher than those recommended in the summary of product characteristics (SmPC) at initiation and during 6 months of follow-up, and no concomitant use of verapamil or diltiazem. RESULTS: Overall, 711 and 506 eligible patients were included in the pre-RMM and post-RMM periods, respectively. The percentage of patients prescribed ivabradine according to the new RMMs increased significantly in the post-RMM period (70.6% and 78.4% in the pre- and post-RMM periods respectively; P value = .0035). The compliance to RMMs increased for all the criteria assessed independently: the proportions of patients with (a) heart rate ≥ 70 bpm at initiation (79.4% and 85.2%, respectively; P value = .0141), (b) no dose higher than the SmPC doses at initiation and during follow-up (92.8% and 94.1%, respectively; P value = .3957), and (c) no concomitance with verapamil or diltiazem (96.1% and 99.2%, respectively; P value = .0007). CONCLUSIONS: The RMMs for ivabradine were well implemented across the five participating European countries confirming a favorable benefit-risk balance of ivabradine in chronic stable angina pectoris.
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Angina Estable/tratamiento farmacológico , Fármacos Cardiovasculares/administración & dosificación , Ivabradina/administración & dosificación , Guías de Práctica Clínica como Asunto , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Fármacos Cardiovasculares/efectos adversos , Estudios de Cohortes , Utilización de Medicamentos , Europa (Continente) , Femenino , Adhesión a Directriz , Humanos , Ivabradina/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Gestión de Riesgos , Adulto JovenRESUMEN
Epidemiological studies on heart failure (HF) using large health care databases are becoming increasingly frequent, as they represent an invaluable opportunity to characterize the importance and risk factors of HF from a population perspective. Nevertheless, because of its complex diagnosis and natural history, the heterogeneous use of the relevant terminology in routine clinical practice, and the limitations of some disease coding systems, HF can be a challenging condition to assess using large health care databases as the main source of information. In this narrative review, we discuss some of the challenges that researchers may face, with a special focus on the identification and validation of chronic HF cases and acute HF decompensations. For each of these challenges, we present some potential solutions inspired by the literature and/or based on our research experience, aimed at increasing the internal validity of research and at informing its interpretation. We also discuss future directions on the field, presenting constructive recommendations aimed at facilitating the conduct of valid epidemiological studies on HF in the coming years.
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Investigación Biomédica/métodos , Bases de Datos Factuales , Insuficiencia Cardíaca/diagnóstico , Almacenamiento y Recuperación de la Información/métodos , Enfermedad Aguda , Enfermedad Crónica , Humanos , Terminología como AsuntoRESUMEN
This study aimed to assess cerebrospinal fluid (CSF) drug concentrations and viral suppression in HIV-1-infected patients on ritonavir-boosted atazanavir (ATV/r) plus lamivudine (3TC) dual therapy. HIV-1-infected adults with suppressed plasma HIV-1 RNA who switched to ATV/r plus 3TC were studied. Total ATV and 3TC concentrations at the end of the dosing interval (C24h), using a validated LC-MS/MS method, and HIV-1 RNA were measured in paired CSF and plasma samples 12 weeks after switching. Ten individuals were included. Median (range) age was 42.5 (33-70) years, time on ART was 39.5 (11-197) months, and time with plasma HIV-1 RNA < 40 copies/mL was 15.5 (6-46) months. At baseline, CSF HIV-1 RNA was < 40 copies/mL in all patients. Twelve weeks after switching to ATV/r plus 3TC, HIV-1 RNA remained at < 40 copies/mL in both plasma and CSF in 9/10 patients. One patient with suboptimal adherence to ART had HIV-1 RNA rebound in both plasma and CSF. The median CSF-to-plasma concentration ratios of ATV and 3TC were 0.013 and 0.417, respectively. Median ATV C24h in CSF was 10.4 (3.7-33.4) ng/mL (in vitro ATV IC50 range, 1-11 ng/mL). Median 3TC C24h in CSF was 43.4 (16.2-99.3) ng/mL (in vitro 3TC IC50 range, 0.68-20.6 ng/mL). Most patients maintained HIV-1 RNA in CSF < 40 copies/mL despite CSF ATV C24h close to or within the IC50 range in the majority. ATV PK data in CSF should be considered and rigorous patient selection is advisable to assure effective CSF viral suppression with this two-drug simplification regimen.
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Fármacos Anti-VIH/líquido cefalorraquídeo , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Adulto , Anciano , Sulfato de Atazanavir/administración & dosificación , Sulfato de Atazanavir/líquido cefalorraquídeo , Quimioterapia Combinada/métodos , Femenino , VIH-1 , Humanos , Lamivudine/administración & dosificación , Lamivudine/líquido cefalorraquídeo , Masculino , Persona de Mediana Edad , ARN Viral/sangre , ARN Viral/líquido cefalorraquídeo , Ritonavir/administración & dosificación , Ritonavir/líquido cefalorraquídeo , Carga Viral/efectos de los fármacosRESUMEN
Doppler echocardiogram provides not only structural information about heart chambers, valves and pericardium but also contributes to functional assessment. A unique feature of this assessment is its variability, not only due to heart disease course but also related to extracardiac conditions. We present a case of primary amyloidosis with two atypical characteristics: left ventricular outflow obstruction and low-grade diastolic dysfunction. Nevertheless, a more typical picture of cardiac amyloidosis was observed in the evolution of the disease coinciding with a second cardiac stressor, emphasizing the necessity of not focusing our attention exclusively to the heart.
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Amiloidosis/diagnóstico , Cardiomiopatías/diagnóstico , Ecocardiografía Doppler/métodos , Función Ventricular Izquierda/fisiología , Obstrucción del Flujo Ventricular Externo/diagnóstico , Amiloidosis/complicaciones , Amiloidosis/fisiopatología , Cardiomiopatías/complicaciones , Cardiomiopatías/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Obstrucción del Flujo Ventricular Externo/etiología , Obstrucción del Flujo Ventricular Externo/fisiopatologíaRESUMEN
BACKGROUND: Pulmonary hypertension (PH) is a common cause of right ventricular (RV) remodeling and functional tricuspid regurgitation (FTR), but incremental pulmonary artery systolic pressure (PASP) does not always correlate with anatomic and functional RV changes. This study aimed to evaluate a noninvasive measure of pulmonary vascular resistance (PVR) for predicting RV dilatation, RV dysfunction, and severity of FTR. METHODS: We prospectively analyzed consecutive stable patients with PASP ≥ 35 mm Hg or any degree of RV dilatation or dysfunction secondary to PH. Noninvasive PVR was calculated based on FTR peak velocity and flow in RV outflow tract. RESULTS: We included 251 patients, aged 72.1 ± 11.4 years, 53% women, 74.9% with type 2 pulmonary hypertension. The mean PASP was 48.3 ± 12.2 mm Hg. Both PASP and PVR significantly correlated with FTR, RV dilatation, and RV systolic dysfunction. After dichotomizing FTR and RV dilatation and systolic dysfunction as nonsignificant vs significant, FTR and RV dilatation were similarly predicted by PASP and PVR, but RV dysfunction was better predicted by PVR (AUC = 0.78 [0.72-0.84] vs 0.66 [0.60-0.73] for PASP, P < 0.001). Patients with low PASP but high PVR showed worse RV and left ventricular function but lower rates of right heart failure and smaller inferior vena cava, compared to patients with high PASP but low PVR. CONCLUSIONS: Noninvasive PVR was superior to PASP for predicting RV systolic dysfunction, but both were similarly associated with RV dilatation or FTR grade. PASP and PVR complement each other to define the echocardiographic findings and clinical status of the patient.
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Presión Arterial/fisiología , Ecocardiografía/métodos , Arteria Pulmonar/fisiopatología , Insuficiencia de la Válvula Tricúspide/fisiopatología , Resistencia Vascular/fisiología , Remodelación Ventricular/fisiología , Anciano , Femenino , Ventrículos Cardíacos , Humanos , Masculino , Estudios Prospectivos , Arteria Pulmonar/diagnóstico por imagen , Índice de Severidad de la Enfermedad , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagenRESUMEN
Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12 months were +105 (95% CI 77-134) in HIV-2+ patients and +202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm3 in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm3/year lower (95% CI 5-44; P = 0.0127) in HIV-2+ patients compared with HIV-1+ patients. Conclusions: A poorer CD4 cell increase during first-line cART was observed in HIV-2+ patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2.
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Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Infecciones por VIH/inmunología , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-2/efectos de los fármacos , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Estudios de Cohortes , Europa (Continente) , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Humanos , Internacionalidad , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Carga ViralRESUMEN
BACKGROUND: The objective of this study was to quantify human immunodeficiency virus (HIV) type 1 RNA decay and dolutegravir (DTG) concentrations in the semen of HIV-infected patients receiving DTG-based first-line therapy. METHODS: This was a prospective, single-arm, open-label study including 15 HIV-1-infected, antiretroviral therapy-naive men starting once-daily treatment with DTG (50 mg) plus abacavir-lamivudine (600/300 mg). HIV-1 RNA was measured in seminal plasma (SP) and blood plasma (BP) at baseline, on days 3, 7, and 14, and at weeks 4, 12, and 24. The HIV-1 RNA decay rate was assessed using nonlinear mixed-effects models. Total and free DTG concentrations were quantified 24 hours after the dose at weeks 4 and 24 by means of a validated liquid chromatography-tandem mass spectrometry method. RESULTS: Viral decay was faster in BP than in SP in the first decay phase (half-life, 4.5 vs 8.6 days; P = .001) with no statistically significant differences in the second phase. HIV-1 RNA suppression (<40 copies/mL) was reached earlier in SP (4 vs 12 weeks; P = .008) due to lower baseline HIV-1 RNA levels. The median total DTG 24 hours after the dose in SP was 119.1 ng/mL (range, 27.2-377 ng/mL), which represents 7.8% of BP exposure. The median DTG free-fraction in SP was 48% of the total drug. Seminal protein-unbound DTG concentrations exceeded the in vitro 50% inhibitory concentration (0.21 ng/mL) by a median of 214-fold. CONCLUSIONS: DTG concentrations in SP are sufficient to contribute to rapid seminal HIV-1 RNA suppression.
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Fármacos Anti-VIH/farmacocinética , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/farmacocinética , Estabilidad del ARN , ARN Viral/metabolismo , Semen/química , Semen/virología , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/análisis , Didesoxinucleósidos/administración & dosificación , Combinación de Medicamentos , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/análisis , Humanos , Lamivudine/administración & dosificación , Masculino , Persona de Mediana Edad , Oxazinas , Proyectos Piloto , Piperazinas , Plasma/química , Estudios Prospectivos , Piridonas , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: It has been suggested that routine CD4 cell count monitoring in human immunodeficiency virus (HIV)-monoinfected patients with suppressed viral loads and CD4 cell counts >300 cell/µL could be reduced to annual. HIV/hepatitis C virus (HCV) coinfection is frequent, but evidence supporting similar reductions in CD4 cell count monitoring is lacking for this population. We determined whether CD4 cell count monitoring could be reduced in monoinfected and coinfected patients by estimating the probability of maintaining CD4 cell counts ≥200 cells/µL during continuous HIV suppression. METHODS: The PISCIS Cohort study included data from 14 539 patients aged ≥16 years from 10 hospitals in Catalonia and 2 in the Balearic Islands (Spain) since January 1998. All patients who had at least one period of 6 months of continuous HIV suppression were included in this analysis. Cumulative probabilities with 95% confidence intervals were calculated using the Kaplan-Meier estimator stratified by the initial CD4 cell count at the period of continuous suppression initiation. RESULTS: A total of 8695 patients were included. CD4 cell counts fell to <200 cells/µL in 7.4% patients, and the proportion was lower in patients with an initial count >350 cells/µL (1.8%) and higher in those with an initial count of 200-249 cells/µL (23.1%). CD4 cell counts fell to <200 cells/µL in 5.7% of monoinfected and 11.1% of coinfected patients. Of monoinfected patients with an initial CD4 cell count of 300-349 cells/µL, 95.6% maintained counts ≥200 cells/µL. In the coinfected group with the same initial count, this rate was lower, but 97.6% of coinfected patients with initial counts >350 cells/µL maintained counts ≥200 cells/µL. CONCLUSIONS: From our data, it can be inferred that CD4 cell count monitoring can be safely performed annually in HIV-monoinfected patients with CD4 cell counts >300 cells/µL and HIV/HCV-coinfected patients with counts >350 cells/µL.
Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , Hepatitis C/epidemiología , Hepatitis C/inmunología , Adolescente , Adulto , Estudios de Cohortes , Coinfección/epidemiología , Coinfección/inmunología , Coinfección/virología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , VIH-1 , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: It is unclear whether metabolic or body composition effects differ between protease inhibitor-based regimens recommended for initial treatment of human immunodeficiency virus (HIV) infection. METHODS: ATADAR is a phase 4, open-label, multicenter, randomized clinical trial. Stable antiretroviral-naive HIV-infected adults were randomly assigned to atazanavir/ritonavir 300/100 mg or darunavir/ritonavir 800/100 mg in combination with tenofovir/emtricitabine daily. Predefined endpoints were treatment or virological failure, drug discontinuation due to adverse effects, and laboratory and body composition changes at 96 weeks. RESULTS: At 96 weeks, 56 (62%) atazanavir/ritonavir and 62 (71%) darunavir/ritonavir patients remained free of treatment failure (estimated difference 8.2%; 95% confidence interval [CI], -.6 to 21.6) and 71 (79%) atazanavir/ritonavir and 75 (85%) darunavir/ritonavir patients remained free of virological failure (estimated difference 6.3%; 95% CI, -.5 to 17.6). Seven patients discontinued atazanavir/ritonavir and 5 discontinued darunavir/ritonavir due to adverse effects. Total and high-density lipoprotein cholesterol similarly increased in both arms, but there was a greater increase in triglycerides in the atazanavir/ritonavir arm. At 96 weeks, body fat (estimated difference 2862.2 gr; 95% CI, 726.7 to 4997.7; P = .0090), limb fat (estimated difference 1403.3 gr; 95% CI, 388.4 to 2418.2; P = .0071), and subcutaneous abdominal adipose tissue (estimated difference 28.4 cm(2); 95% CI, 1.9 to 55.0; P = .0362) increased more in the atazanavir/ritonavir arm than in darunavir/ritonavir arm. Body fat changes in the atazanavir/ritonavir arm were associated with higher insulin resistance. CONCLUSIONS: We found no major differences between atazanavir/ritonavir and darunavir/ritonavir in efficacy, clinically relevant side effects, or plasma cholesterol fractions. However, atazanavir/ritonavir led to higher triglycerides and more total and subcutaneous fat than darunavir/ritonavir. Also, fat gains with atazanavir/ritonavir were associated with insulin resistance. Clinical Trials Registration. NCT01274780.
Asunto(s)
Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Composición Corporal/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/efectos adversos , Inhibidores de la Proteasa del VIH/uso terapéutico , Adulto , Femenino , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Carga ViralRESUMEN
OBJECTIVES: Maximizing ART efficiency is of growing interest. This study assessed the efficacy, safety, pharmacokinetics and economics of a darunavir dose-reduction strategy. METHODS: This was a multicentre, randomized, open-label clinical trial in HIV-infected patients with plasma HIV-1 RNA <50 copies/mL while receiving triple ART including 800 mg of darunavir once daily. Participants were randomized to continue 800 mg of darunavir (DRV800) or to 600 mg of darunavir (DRV600), both once daily. Treatment failure was defined as two consecutive HIV-1 RNA determinations >50 copies/mL or discontinuation of study treatment by week 48. The study was registered at https://www.clinicaltrialsregister.eu (trial number 2011-006272-39). RESULTS: Fifty participants were allocated to each arm. The mean (SD) CD4+ T cell count at baseline was 562 (303) cells/mm(3) and HIV-1 RNA had been <50 copies/mL for a median (IQR) of 106.9 (43.4-227.9) weeks before enrolment. At week 48 no treatment failure had occurred in 45/50 (90%) DRV600 patients and in 47/50 (94%) DRV800 patients (difference -4%; 95% CI lower limit, -12.9%). When only patients with virological data were considered, that endpoint was met by 45/48 (94%) in the DRV600 arm and 47/49 (96%) in the DRV800 arm (difference -2.2%; 95% CI lower limit, -9.6%). Darunavir exposure was similar in the two arms. The average reduction in annual cost per successfully treated DRV600-arm patient was US$7273. CONCLUSIONS: The efficacy of a darunavir daily dose of 600 mg seemed to be similar to the efficacy of the standard 800 mg dose in virologically suppressed HIV-infected patients on triple ART. This strategy can potentially translate to substantial savings in the cost of care of HIV-infected patients.
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Antirretrovirales/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , VIH-1/aislamiento & purificación , Quimioterapia de Mantención/métodos , Sulfonamidas/administración & dosificación , Carga Viral , Adulto , Antirretrovirales/efectos adversos , Antirretrovirales/economía , Antirretrovirales/farmacocinética , Darunavir , Femenino , Humanos , Quimioterapia de Mantención/efectos adversos , Quimioterapia de Mantención/economía , Masculino , Persona de Mediana Edad , Plasma/virología , Sulfonamidas/efectos adversos , Sulfonamidas/economía , Sulfonamidas/farmacocinética , Resultado del TratamientoRESUMEN
OBJECTIVES: The aim of this study was to analyse factors associated with progression to AIDS/death in severely immunosuppressed HIV-infected patients receiving ART. METHODS: This study included naive patients from the PISCIS Cohort with CD4 <200 cells/mm(3) at enrolment and who initiated ART consisting of two nucleoside analogues plus either a PI or an NNRTI between 1998 and 2011. The PISCIS Cohort is a multicentre, observational study of HIV-infected individuals aged >18 years followed at 14 participating hospitals in Catalonia and the Balearic Islands (Spain). Clinical and laboratory parameters were assessed every 3-4 months during follow-up. Cox regression models were used to assess the effect of CD4 and viral load on the risk of progression to AIDS/death, adjusting for baseline variables and confounders. RESULTS: 2295 patients were included and, after 5 years, 69.9% reached CD4 ≥200 cells/mm(3), 64.4% had an undetectable viral load and 482 (21%) progressed to AIDS/death. The lowest rate of disease progression was found in patients who reached both immunological and viral responses during follow-up, regardless of their baseline situation (1.9% in baseline CD4 >100 cells/mm(3) and viral load <5 log copies/mL; 2.3% in baseline CD4 ≤100 cells/mm(3) and/or viral load >5 log copies/mL). Achieving a CD4 count ≥200 cells/mm(3) was the main predictor of decreased progression to AIDS/death. In those not reaching this CD4 threshold, virological response reduced disease progression by half. CONCLUSIONS: Even in the worse baseline scenario of CD4 ≤100 cells/mm(3) and high baseline viral loads, positive virological and immunological responses were associated with dramatic decreases in progression.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/patología , Carga Viral , Adulto , Recuento de Linfocito CD4 , Progresión de la Enfermedad , Femenino , Infecciones por VIH/mortalidad , Humanos , Masculino , Persona de Mediana Edad , España , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVES: The objective of this study was to assess whether a lower dose than the currently used one of darunavir/ritonavir might achieve good CSF concentrations and contribute to inhibition of CNS viral replication. PATIENTS AND METHODS: This was a substudy of a randomized, open, multicentre study (eudraCT 2011-006272-39), comparing the efficacy and safety of 800/100 mg of darunavir/ritonavir (darunavir 800) versus 600/100 mg of darunavir/ritonavir (darunavir 600) once daily plus tenofovir/emtricitabine or abacavir/lamivudine in 100 virologically suppressed patients. Paired blood and CSF samples were obtained. Total plasma darunavir concentrations were determined by HPLC, and CSF concentrations by liquid chromatography-tandem MS. Viral load (VL) was determined in plasma and CSF (limit of detectionâ=â40 copies/mL) by PCR. RESULTS: Sixteen patients were enrolled. The median (range) of darunavir CSF concentrations in darunavir 600 (nâ=â8) and darunavir 800 (nâ=â8) patients was 17.08 (5.79-30.19) and 13.23 (3.47-32.98) ng/mL, respectively (Pâ=â0.916). The median (range) darunavir CSF:plasma ratio was 0.010 (0.005-0.022) in darunavir 600 patients and 0.008 (0.004-0.017) in the darunavir 800 arm (Pâ=â0.370). All 16 patients had a VLâ<â40 copies/mL in plasma and 14 had a VLâ<â40 copies/mL in CSF. Of the two patients with detectable CSF VL (280 copies/mL and 159 copies/mL), one was receiving darunavir 600 and the other darunavir 800 plus tenofovir/emtricitabine. Of note, these patients had the lowest CSF darunavir concentrations in their respective groups: 5.79 ng/mL (802 ng/mL in plasma) and 3.47 ng/mL (958 ng/mL in plasma). CONCLUSIONS: Darunavir CSF and plasma concentrations were comparable between the two arms. However, one patient from each group (with the lowest CSF darunavir concentrations in their respective groups) had detectable CSF VL despite undetectable plasma VL.