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1.
J Med Virol ; 86(4): 678-86, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24482297

RESUMEN

Multiple human proteins have been shown to both support and restrict viral replication, and confirmation of virus-associated changes in the expression of these genes is relevant for future therapeutic efforts. In this study a well-characterized panel of 49 individuals either infected with HIV-1 or uninfected was compiled and analyzed for the effect of HIV infection status, viral load, and antiretroviral treatment on specific gene expression. mRNA was extracted and reverse transcribed from purified CD4+ cells, and quantitative real-time PCR was utilized to scrutinize differences in the expression of four host genes that have been demonstrated to either stimulate (HSP90 and LEDGF/p75) or restrict (p21/WAF1 and APOBEC3G) proviral integration. HIV infection status was associated with slight to moderate alterations in the expression of all four genes. After adjusting for age, mRNA expression levels of HSP90, LEDGF/p75 and APOBEC3G were found to all be decreased in infected patients compared to healthy controls by 1.43-, 1.26-, and 4.71-fold, respectively, while p21/WAF1 expression was increased 2.35-fold. Furthermore, individuals receiving raltegravir exhibited a 1.28-fold reduction in LEDGF/p75 compared to those on non-raltegravir antiretroviral treatment. Identification of these and similar HIV-induced changes in gene expression may be valuable for delineating the extent of host cell molecular mechanisms stimulating viral replication.


Asunto(s)
Inhibidor p21 de las Quinasas Dependientes de la Ciclina/biosíntesis , Citidina Desaminasa/biosíntesis , Infecciones por VIH/inmunología , Proteínas HSP90 de Choque Térmico/biosíntesis , Péptidos y Proteínas de Señalización Intercelular/biosíntesis , Desaminasa APOBEC-3G , Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Adulto , Linfocitos T CD4-Positivos/inmunología , Niño , Estudios Transversales , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Citidina Desaminasa/genética , Femenino , Expresión Génica , Regulación de la Expresión Génica , Infecciones por VIH/tratamiento farmacológico , VIH-1/genética , Proteínas HSP90 de Choque Térmico/genética , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , Persona de Mediana Edad , Pirrolidinonas/uso terapéutico , ARN Mensajero/biosíntesis , Raltegravir Potásico , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética , Adulto Joven
2.
J Infect Dis ; 206(3): 421-30, 2012 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-22615311

RESUMEN

BACKGROUND: The safety and immunogenicity of high-dose pandemic H1N1 (pH1N1) vaccination in perinatally human immunodeficiency virus type 1 (HIV-1)-infected children, adolescents, and young adults are unknown. METHODS: Two 30-µg doses of 2009 Novartis pH1N1 monovalent vaccine (Fluvirin) were administered 21-28 days apart to perinatally HIV-1-infected children, adolescents, and young adults. Antibodies were measured by hemagglutination inhibition (HAI) assay at baseline, 21-28 days after first vaccination, 7-13 days after the second vaccination, and 7 months after the first vaccination. RESULTS: Among the 155 participants, 54 were aged 4-8 years, 51 were aged 9-17 years, and 50 were aged 18-24 years. After 2 doses of Fluvirin, seroresponse (≥ 4-fold rise in HAI titers) was demonstrated in 79.6%, 84.8%, and 83% of participants in the aforementioned age groups, respectively, and seroprotection (HAI titers ≥ 40) was shown in 79.6%, 82.6%, and 85.1%, respectively. Of those lacking seroresponse (n = 43) or seroprotection (n = 37) after the first vaccination, 46.5% and 40.5% achieved seroresponse or seroprotection, respectively, after the second vaccination. Among participants who lacked seroprotection at entry, a "complete response" (both seroresponse and seroprotection) after first vaccination was associated with higher baseline log(10) HAI titer and non-Hispanic ethnicity. No serious vaccine-related events occurred. CONCLUSION: Two doses of double-strength pH1N1 vaccine are safe and immunogenic and may provide improved protection against influenza in perinatally HIV-1-infected children and youth. CLINICAL TRIALS REGISTRATION: NCT00992836.


Asunto(s)
Infecciones por VIH/complicaciones , VIH-1 , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/prevención & control , Vacunas Virales/efectos adversos , Vacunas Virales/inmunología , Adolescente , Niño , Preescolar , Relación Dosis-Respuesta Inmunológica , Infecciones por VIH/inmunología , Humanos , Esquemas de Inmunización , Transmisión Vertical de Enfermedad Infecciosa , Pandemias , Vacunas Virales/administración & dosificación , Adulto Joven
3.
Animals (Basel) ; 13(14)2023 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-37508168

RESUMEN

Farmers are continually looking for new, reliable, objective, and non-invasive methods for evaluating the conditions of ewes. Live weight (LW) and body condition score (BCS) are used by farmers as a basis to determine the condition of the animal. Body composition is an important aspect of monitoring animal condition. The body composition is the amount of fat, muscle, and bone; knowing the amount of each is important because the information can be used for better strategic management interventions. Experiments were conducted to establish the relationship between body composition and body parameters at key life stages (weaning and pre-mating), using measurements automatically determined by an image processing application for 88 Coopworth ewes. Computerized tomography technology was used to determine the body composition. Multivariate linear regression (MLR), artificial neural network (ANN), and regression tree (RT) statistical analysis methods were used to develop a relationship between the body parameters and the body composition. A subset of data was used to validate the predicted model. The results showed a correlation between fat, muscle, and bone determined by CT and the fat, muscle, and bone weight estimated by the live weight and body parameters calculated using the image processing application, with r2 values of 0.90 for fat, 0.72 for muscle, and 0.50 for bone using ANN. From these results, farmers can utilize these measurements to enhance nutritional and management practices.

4.
Microbiol Spectr ; 11(1): e0370922, 2023 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-36688648

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binding antibody (Ab) levels following vaccination or natural infection could be used as a surrogate for immune protection if results of serological assays were standardized to yield quantitative results using an international standard. Using a bead-based serological assay (Luminex xMAP), anti-receptor binding domain (anti-RBD) Ab levels were determined for 1,450 participants enrolled in the Los Angeles Pandemic Surveillance Cohort (LAPSC) study. For 123 participants, SARS-CoV-2 binding antibody unit (BAU) levels were also quantified using WHO standards and then compared to the semiquantitative results. Samples were chosen to represent the range of results and time from vaccination. Antibody levels and decay rates were then compared using unadjusted and adjusted linear regression models. The linear range of the assay used in this study was determined to be 300 to 5,000 mean fluorescence intensity units (MFI). Among the fully vaccinated groups (vaccinated only and vaccinated with past infection), 84.8% had anti-RBD MFI values above the linear range of >5,000 MFI, and 33.8% had values of >15,000 MFI. Among vaccinated participants with past infection (hybrid immunity), 97% had anti-RBD values of >5,000 MFI and 70% (120/171) had anti-RBD values of >15,000 MFI. In the subgroup quantified using the WHO control, BAU levels were significantly higher than the semiquantitative MFI results. In vaccinated participants, Ab decay levels were similar between infected and noninfected groups (P = 0.337). These results demonstrate that accurate quantitation is possible if standardized with an international standard. BAU can then be compared over time or between subjects and would be useful in clinical decision making. IMPORTANCE Accurate quantification of SARS-CoV-2-specific antibodies can be achieved using a universal standard with sample dilution within the linear range. With hybrid immunity being now common, it is critical to use protocols adapted to high Ab levels to standardize serological results. We validated this approach with the Los Angeles Pandemic Surveillance Cohort by comparing the antibody decay rates in vaccinated participants and vaccinated infected participants.


Asunto(s)
COVID-19 , Vacunas , Humanos , SARS-CoV-2 , COVID-19/prevención & control , Anticuerpos Antivirales , Vacunación , Organización Mundial de la Salud
5.
J Gerontol Nurs ; 38(3): 18-27; quiz 28-9, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22329392

RESUMEN

Protein calorie malnutrition (PCM) is common and often undiagnosed in older adults. Left untreated, PCM carries both clinical and financial risks, including decreased quality of life, declining functionality, the inability to live independently, and increased health care costs. The prevalence of PCM in older adults calls for a systematic and standardized approach to nutrition screening that includes the use of a validated screening tool. Recommended by international organizations, the Mini Nutritional Assessment® (MNA) is highly specific and reliable and the most well-validated nutrition screening tool for adults 65 and older. Simple, noninvasive, inexpensive, and easy for nurses and other clinicians to use, the newest MNA-short form (MNA-SF) can quickly and easily identify older adults who are at risk for malnutrition or malnourished. Nurses are key players in successful malnutrition screening in hospitals, long-term care, home care, and community settings. It is strongly recommended that nurses incorporate the newest MNA-SF into all practice settings where older adults receive care.


Asunto(s)
Enfermería Basada en la Evidencia , Evaluación Geriátrica , Desnutrición , Evaluación Nutricional , Anciano , Educación Continua en Enfermería , Humanos
6.
Lancet HIV ; 9(5): e332-e340, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35489377

RESUMEN

BACKGROUND: Safe and potent antiretroviral medications in child-friendly formulations are needed to treat young children living with HIV-1. We aimed to select dosing for a dispersible tablet formulation of dolutegravir that achieved pharmacokinetic exposures similar to those in adults, and was safe and well tolerated in young children. METHODS: International Maternal Pediatric Adolescent AIDS Clinical Trial (IMPAACT) P1093 is a phase 1-2 ongoing multicentre, open-label, non-comparative study of dolutegravir. A 5 mg dispersible tablet formulation of dolutegravir was studied in children aged 4 weeks to less than 6 years old, weighing at least 3 kg, with HIV RNA of greater than 1000 copies per mL and no previous treatment with integrase strand transfer inhibitor recruited from IMPAACT clinical research sites in Africa, the Americas, and Asia. Doses were selected on the basis of intensive pharmacokinetic evaluation on days 5-10, with safety and tolerability assessed up to 48 weeks. The primary objectives of this study are to evaluate the pharmacokinetics of dolutegravir in combination with optimised background therapy and to establish the dose of dolutegravir that achieves the targeted 24-h trough concentration and 24-h area under the curve for infants, children, and adolescents with HIV-1, to establish the safety and tolerability of dolutegravir at 24 and 48 weeks, and to select a dose that achieves similar exposure to the dolutegravir 50 mg once daily dose in adults. This analysis included participants treated with the proposed dose of dolutegravir dispersible tablets in two stages for each of three age cohorts. This trial is registered at ClinicalTrials.gov (NCT01302847) and is ongoing. FINDINGS: We recruited 181 participants from April 20, 2011, to Feb 19, 2020; of these, 96 received dolutegravir dispersible tablets. This analysis included 73 (35, 48% female) participants who received the final proposed dose with median (range) age of 1 year (0·1 to 6·0), weight (minimum-maximum) of 8·5 kg (3·7 to 18·5), plasma HIV-1 RNA concentration of 4·2 log10 copies per mL (2·1 to 7·0), and CD4% of 24·0% (0·3 to 49·0); 64 (87·7%) were treatment-experienced. The selected dose within each age cohort (≥2 years to <6 years, ≥6 months to <2 years of age and ≥4 weeks to <6 months) achieved geometric mean trough (ng/mL) of 688, 1179, and 1446, and 24 h area-under-the-curve (h·mg/L) of 53, 74, and 65, respectively. No grade 3 or worse adverse events were attributed to dolutegravir. INTERPRETATION: In this study, the proposed once daily dosing of dolutegravir dispersible tablets provided drug exposures similar to those for adults, and was safe and well tolerated. These data support the use of dolutegravir dispersible tablets as first-line or second-line treatment for infants and children aged less than 6 years living with HIV-1. FUNDING: National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Mental Health, and ViiV Healthcare-GlaxoSmithKline.


Asunto(s)
Infecciones por VIH , Inhibidores de Integrasa VIH , Seropositividad para VIH , VIH-1 , Adolescente , Adulto , Antivirales/uso terapéutico , Niño , Preescolar , Femenino , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Seropositividad para VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos , Humanos , Lactante , Masculino , Oxazinas , Piperazinas , Piridonas , ARN/uso terapéutico , Comprimidos
7.
J Pediatric Infect Dis Soc ; 9(2): 159-165, 2020 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-30951600

RESUMEN

BACKGROUND: P1093 is an ongoing phase I/II multicenter open-label study of dolutegravir plus an optimized background regimen in age-defined pediatric cohorts; here we report the long-term safety and virologic efficacy outcomes for the oldest cohort. METHODS: The study enrolled human immunodeficiency virus type 1 (HIV-1)-infected treatment-experienced adolescents aged 12 to <18 years, with an HIV-1 RNA level ≥1000 copies/mL . Cumulative safety and HIV-1 RNA outcomes were assessed once the last enrolled participant reached 144 weeks of follow-up. RESULTS: Among 23 adolescents enrolled, 16 remained in the study at least 144 weeks; the median follow-up was 153 weeks (range, 55-193 weeks). Dolutegravir was well tolerated, with grade 3 clinical adverse events in 5 participants, grade 3 laboratory abnormalities in 3, and grade 4 laboratory abnormalities in 1; none of the adverse events or abnormalities were judged to be treatment related. In an-intent-to-treat analysis, an HIV-1 RNA level <400 copies/mL at week 144 was achieved in 43% (10 of 23 participants; 95% confidence interval, 23.2%-65.5%); in addition, 35% (8 of 23; 16.4%-57.3%) had an HIV-1 RNA level <50 copies/mL. Nine participants (39%) discontinued study treatment before 144 weeks, but none because of adverse events or drug intolerance. All participants with sustained virologic control had excellent adherence; most who experienced virologic failure had adherence levels <90%. HIV-1 genotypic drug resistance testing was available at time of failure from 6 participants; 1 had evolution in integrase resistance with E138T, S147G, and R263K mutations at week 192 and phenotypic dolutegravir resistance of a 5.1-fold change. CONCLUSIONS: Dolutegravir plus an optimized background regimen seemed safe, well tolerated, and efficacious in this cohort of treatment-experienced HIV-1-infected adolescents. Adherence remains problematic in this population. CLINICAL TRIALS REGISTRATION: NCT01302847.


Asunto(s)
Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , VIH-1 , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Mutación , Oxazinas/uso terapéutico , Piperazinas/uso terapéutico , Piridonas/uso terapéutico , Adolescente , Antirretrovirales/uso terapéutico , Niño , Quimioterapia Combinada , Femenino , Infecciones por VIH/virología , Inhibidores de Integrasa VIH/efectos adversos , VIH-1/genética , VIH-1/aislamiento & purificación , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Humanos , Masculino , Cumplimiento de la Medicación , Oxazinas/efectos adversos , Piperazinas/efectos adversos , Piridonas/efectos adversos , ARN Viral/sangre , Resultado del Tratamiento , Carga Viral
8.
Lancet HIV ; 7(5): e322-e331, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32386720

RESUMEN

BACKGROUND: Although antiretroviral regimens containing integrase inhibitors rapidly suppress HIV viral load in non-pregnant adults, few published data from randomised controlled trials have compared the safety and efficacy of any integrase inhibitor to efavirenz when initiated during pregnancy. We compared safety and efficacy of antiretroviral therapy with either raltegravir or efavirenz in late pregnancy. METHODS: An open-label, randomised controlled trial was done at 19 hospitals and clinics in Argentina, Brazil, South Africa, Tanzania, Thailand, and the USA. Antiretroviral-naive pregnant women (20-<37 weeks gestation) living with HIV were assigned to antiretroviral regimens containing either raltegravir (400 mg twice daily) or efavirenz (600 mg each night) plus lamivudine 150 mg and zidovudine 300 mg twice daily (or approved alternative backbone regimen), using a web-based, permuted-block randomisation stratified by gestational age and backbone regimen. The primary efficacy outcome was plasma HIV viral load below 200 copies per mL at (or near) delivery. The primary efficacy analysis included all women with a viral load measurement at (or near) delivery who had viral load of at least 200 copies per mL before treatment and no genotypic resistance to any study drugs; secondary analyses eliminated these exclusion criteria. The primary safety analyses included all women who received study drug, and their infants. This trial is registered with Clinicaltrials.gov, number NCT01618305. FINDINGS: From Sep 5, 2013, to Dec 11, 2018, 408 women were enrolled (206 raltegravir, 202 efavirenz) and 394 delivered on-study (200 raltegravir, 194 efavirenz); 307 were included in the primary efficacy analysis (153 raltegravir, 154 efavirenz). 144 (94%) women in the raltegravir group and 129 (84%) in the efavirenz group met the primary efficacy outcome (absolute difference 10%, 95% CI 3-18; p=0·0015); the difference primarily occurred among women enrolling later in pregnancy (interaction p=0·040). Frequencies of severe or life-threatening adverse events were similar among mothers (30% in each group; 61 raltegravir, 59 efavirenz) and infants (25% in each group; 50 raltegravir, 48 efavirenz), with no treatment-related deaths. INTERPRETATION: Our findings support major guidelines. The integrase inhibitor dolutegravir is currently a preferred regimen for the prevention of perinatal HIV transmission with raltegravir recommended as a preferred or alternative integrase inhibitor for pregnant women living with HIV. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development and National Institute of Allergy and Infectious Diseases.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Benzoxazinas/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Raltegravir Potásico/uso terapéutico , Adulto , Alquinos , Fármacos Anti-VIH/efectos adversos , Benzoxazinas/efectos adversos , Ciclopropanos , Quimioterapia Combinada , Femenino , Infecciones por VIH/prevención & control , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Lamivudine/uso terapéutico , Evaluación de Resultado en la Atención de Salud , Embarazo , Raltegravir Potásico/efectos adversos , Carga Viral/efectos de los fármacos , Adulto Joven , Zidovudina/uso terapéutico
9.
Nutr Clin Pract ; 23(4): 373-82, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18682588

RESUMEN

There is agreement among international nutrition organizations and healthcare accrediting organizations that nutrition screening is essential to identify patients needing further nutrition assessment to determine appropriate nutrition intervention. Numerous nutrition screening tools are used in hospitals, but many, if not most, have never been validated for the care setting, patient population, or outcome they strive to identify. Thus, it is unclear if they appropriately identify patients who truly need further nutrition assessment and, potentially, intervention. Several nutrition screening tools reported in the literature have been validated in a variety of care settings and patient populations and have been shown to achieve the desired outcome. These tools include the Malnutrition Universal Screening Tool, Nutritional Risk Screening 2002, Mini Nutritional Assessment, Short Nutritional Assessment Questionnaire, Malnutrition Screening Tool, and the Subjective Global Assessment. It is important for clinicians to understand how the tools were validated and for which population and care setting they were developed, and to determine if the tool might be appropriate for use in their institution.


Asunto(s)
Pacientes Internos , Desnutrición/diagnóstico , Tamizaje Masivo/métodos , Evaluación Nutricional , Estado Nutricional , Humanos , Encuestas y Cuestionarios
10.
Nutr Clin Pract ; 23(4): 388-96, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18682590

RESUMEN

In the early 1990s, the Mini Nutritional Assessment (MNA; Nestle Nutrition, Vevey, Switzerland) was developed for nutrition screening in the elderly. Since then, it became the most established and widespread screening tool for older persons and has been translated into many different languages. The MNA shows prognostic relevance with regard to functionality, morbidity, and mortality of the elderly in different settings. This article recalls the development of the MNA with its short form (MNA-SF) and reviews the literature, focusing on the most recent publications. Specific features of the application of the MNA in different settings (community, nursing home, hospital) are considered. Minor shortcomings of the tool, such as the resources and the cooperation necessary for completion of the MNA, are discussed. Future options for the adaptation of this valuable tool are briefly characterized.


Asunto(s)
Evaluación Geriátrica/métodos , Desnutrición/diagnóstico , Tamizaje Masivo/métodos , Tamizaje Masivo/tendencias , Evaluación Nutricional , Encuestas y Cuestionarios , Anciano , Anciano de 80 o más Años , Envejecimiento , Evaluación Geriátrica/historia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Tamizaje Masivo/historia , Persona de Mediana Edad , Estado Nutricional , Encuestas y Cuestionarios/normas
11.
Semin Oncol Nurs ; 34(5): 454-464, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30413356

RESUMEN

OBJECTIVE: To introduce effectiveness of tumor treating fields (TTFields), how to care for the patient with this type of treatment, and the critical role the nurse plays in educating the patient about this innovative treatment. DATA SOURCES: Published research and articles in both nursing and medical journals. CONCLUSION: TTFields are an antimitotic therapy delivered via transducer arrays that are worn on the scalp to treat newly diagnosed and recurrent glioblastoma, the most aggressive primary brain cancer. Oncology nurses are integral in educating and supporting the patient in its use and managing its of treatment. IMPLICATIONS FOR NURSING PRACTICE: Nurses are on the front line of educating the patient, caregivers, and the larger body of clinicians who deliver care to these patients. Education provided by nurses increases the patients' knowledge, and thus compliance, as well as the overall outcome through proper usage of TTFields.


Asunto(s)
Neoplasias Encefálicas/terapia , División Celular/efectos de la radiación , Terapia por Estimulación Eléctrica/métodos , Glioblastoma/terapia , Glioma/terapia , Recurrencia Local de Neoplasia/terapia , Enfermería Oncológica/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad
12.
J Neurosci Nurs ; 50(3): 124-128, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29727391

RESUMEN

During the past 50 years, there have been more than 100 articles published in the Journal of Neuroscience Nursing covering the topic of neuro-oncology. This article will explore the historical implications and milestones from these articles. The analysis highlights the scope and depth of the many articles as they relate to the advancements in neuro-oncology.


Asunto(s)
Aniversarios y Eventos Especiales , Neoplasias Encefálicas/enfermería , Neoplasias Encefálicas/terapia , Enfermería en Neurociencias/historia , Enfermería Oncológica/historia , Neoplasias Encefálicas/historia , Historia del Siglo XX , Historia del Siglo XXI , Humanos , Neurología/historia
13.
Pediatr Infect Dis J ; 36(1): 53-60, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27749649

RESUMEN

BACKGROUND: Human immunodeficiency virus (HIV)-infected children receiving antiretroviral therapy (ART) have increased prevalence of hyperlipidemia and risk factors for cardiovascular disease. No studies have investigated the efficacy and safety of statins in this population. METHODS: HIV-infected youth 10 to <24 years of age on stable ART with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL for ≥6 months initiated atorvastatin 10 mg once daily. Atorvastatin was increased to 20 mg if LDL-C efficacy criteria (LDL-C < 110 mg/dL or decreased ≥30% from baseline) were not met at week 4. Primary outcomes were safety and efficacy. RESULTS: Twenty-eight youth initiated atorvastatin; 7 were 10-15 years and 21 were 15-24 years. Mean baseline LDL-C was 161 mg/dL (standard deviation 19 mg/dL). Efficacy criteria were met at week 4 by 17 of 27 (63%) participants. Atorvastatin was increased to 20 mg in 10 participants. Mean LDL-C decreased from baseline by 30% (90% confidence interval: 26%, 35%) at week 4, 28% (90% confidence interval: 23%, 33%) at week 24 and 26% (90% confidence interval: 20%, 33%) at week 48. LDL-C was less than 110 mg/dL in 44% at week 4, 42% at week 12 and 46% at weeks 24 and 48. Total cholesterol, non high-density lipoprotein (non-HDL)-C and apolipoprotein B decreased significantly, but IL-6 and high-sensitivity C-reactive protein did not. Two participants in the younger age group discontinued study for toxicities possibly related to atorvastatin. CONCLUSIONS: Atorvastatin lowered total cholesterol, LDL-C, non HDL-C and apolipoprotein B in HIV-infected youth with ART-associated hyperlipidemia. Atorvastatin could be considered for HIV-infected children with hyperlipidemia, but safety monitoring is important particularly in younger children.


Asunto(s)
Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/uso terapéutico , Atorvastatina/efectos adversos , Atorvastatina/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hiperlipidemias/complicaciones , Adolescente , Adulto , Proteína C-Reactiva/análisis , Niño , Femenino , Humanos , Masculino , Adulto Joven
14.
J Acquir Immune Defic Syndr ; 71(2): 172-80, 2016 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-26761519

RESUMEN

OBJECTIVES: Hepatitis C virus (HCV) infection causes an alteration in T-cell maturation and activation in patients coinfected with human immunodeficiency virus (HIV). Because interleukin 7 (IL-7) is a major cytokine controlling T-cell homeostasis, we analyzed the potential influence of HCV coinfection on circulating IL-7 levels in HIV-infected women before and after highly active antiretroviral therapy (HAART). DESIGN AND METHODS: This prospective study included 56 HIV monoinfected, 55 HIV/HCV coinfected without HCV viremia, 132 HIV/HCV coinfected with HCV viremia, and 61 HIV/HCV-uninfected women for whom plasma levels of IL-7 were determined by enzyme-linked immunosorbent assay at 1 or more follow-up visits before and after HAART. Cross-sectional analyses of the associations between plasma IL-7 levels and HCV infection, demographic, clinical, and immunologic characteristics were evaluated using univariate and multivariate linear regression models before and after HAART. RESULTS: In multivariate models, IL-7 levels were significantly higher in coinfected HCV viremic women than in HIV monoinfected women (multiplicative effect = 1.48; 95% confidence interval: 1.01 to 2.16; P = 0.04) before HAART, but were similar between these two groups among women after HAART. In addition to HCV viremia, higher IL-7 levels were associated with older age (P = 0.02), lower CD4(+) T-cell count (P = 0.0007), and higher natural killer T-cell count (P = 0.02) in women before HAART. Among HAART-treated women, only lower CD4(+) T-cell count was significantly associated with IL-7 level (P = 0.006). CONCLUSIONS: Our data demonstrate that in HIV-infected women, circulating levels of IL-7 are strongly associated with CD4 T-cell depletion both before and after HAART. Our data also demonstrate that HCV viremia increases circulating IL-7 levels before HAART but not after HAART in coinfected women. This suggests that the effect of HCV on lymphopenia is abrogated by HAART.


Asunto(s)
Coinfección , Infecciones por VIH/inmunología , VIH-1/inmunología , Hepacivirus/inmunología , Hepatitis C/inmunología , Interleucina-7/sangre , Adulto , Terapia Antirretroviral Altamente Activa , Linfocitos T CD4-Positivos/inmunología , Estudios Transversales , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/complicaciones , Humanos , Persona de Mediana Edad , Células T Asesinas Naturales , Estudios Prospectivos , Viremia
15.
J Clin Pharmacol ; 55(7): 798-808, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25683232

RESUMEN

Few studies have characterized longitudinal female plasma and genital antiretroviral pharmacokinetics and pharmacodynamics. Among 20 regimen-naive HIV-infected adult women initiating atazanavir-based therapy (n = 9) or efavirenz-based therapy (n = 11), we measured blood CD4+ T lymphocytes, and paired plasma and genital HIV RNA and atazanavir or efavirenz 2 days before starting therapy and 2, 4, 7, 10, 21, 28, 60, 120, and 180 days after. The mean (range) log10 baseline plasma viral load was 4.89 copies/mL (2.64-6.09 copies/mL), and genital was3.30 (1.60-5.00). In the atazanavir and efavirenz groups, mean (SD) days to a 50% decrease in plasma viral load was 8.2 (4.9) versus 9.3 (7.4), P = .7, and in the genital tract it was 7.3 (3.5) versus 9.3 (7.7), P = .5. The median (interquartile range) plasma:genital concentration ratio for atazanavir was 0.11 (0.001-0.46) versus 0.34 (0.05-1.30) for efavirenz, P = .5. Average plasma efavirenz or atazanavir concentrations over time did not affect virologic response. Blood CD4+ percentages increased by +2.3 (P = .06) and +3.0 (P = .003) for every 1 mg/L increase in average plasma and genital drug concentration, respectively. Plasma and genital viral pharmacodynamics were similar between the groups and independent of average concentrations, but blood CD4+ response was related in particular to genital extravascular drug concentrations.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Sulfato de Atazanavir/administración & dosificación , Benzoxazinas/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Adulto , Alquinos , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/farmacología , Sulfato de Atazanavir/farmacocinética , Sulfato de Atazanavir/farmacología , Benzoxazinas/farmacocinética , Benzoxazinas/farmacología , Recuento de Linfocito CD4 , Estudios de Cohortes , Ciclopropanos , Quimioterapia Combinada , Femenino , Humanos , Persona de Mediana Edad , ARN Viral/sangre , Carga Viral/efectos de los fármacos , Adulto Joven
16.
PLoS One ; 10(3): e0120474, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25794163

RESUMEN

BACKGROUND: We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study. METHODS: Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry. RESULTS: Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets. CONCLUSIONS: In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Coinfección , Infecciones por Citomegalovirus/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Recuento de Linfocitos , Subgrupos de Linfocitos T/inmunología , Adolescente , Antígenos CD/metabolismo , California , Niño , Preescolar , Infecciones por Citomegalovirus/virología , Femenino , Infecciones por VIH/virología , Humanos , Inmunidad Celular , Inmunofenotipificación , Lactante , Activación de Linfocitos/inmunología , Masculino , Resultado del Tratamiento , Carga Viral
17.
Hum Vaccin Immunother ; 9(5): 957-68, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23370281

RESUMEN

HIV-infected individuals have poor responses to inactivated influenza vaccines. To evaluate the potential role of regulatory T (Treg) and B cells (Breg), we analyzed their correlation with humoral and cell-mediated immune (CMI) responses to pandemic influenza (pH1N1) monovalent vaccine in HIV-infected children and youth. Seventy-four HIV-infected, 4- to 25-y old participants in a 2-dose pH1N1 vaccine study had circulating and pH1N1-stimulated Treg and Breg measured by flow cytometry at baseline, post-dose 1 and post-dose 2. Concomitantly, CMI was measured by ELISPOT and flow cytometry; and antibodies by hemagglutination inhibition (HAI). At baseline, most of the participants had pH1N1-specific IFNγ ELISPOT responses, whose magnitude positively correlated with the baseline pH1N1, but not with seasonal H1N1 HAI titers. pH1N1-specific IFNγ ELISPOT responses did not change post-dose 1 and significantly decreased post-dose 2. In contrast, circulating CD4+CD25+% and CD4+FOXP3+% Treg increased after vaccination. The decrease in IFNγ ELISPOT results was marginally associated with higher pH1N1-specific CD19+FOXP3+ and CD4+TGFß+% Breg and Treg, respectively. In contrast, increases in HAI titers post-dose 1 were associated with significantly higher circulating CD19+CD25+% post-dose 1, whereas increases in IFNγ ELISPOT results post-dose 1 were associated with higher circulating CD4+/C8+CD25+FOXP3+%. In conclusion, in HIV-infected children and youth, influenza-specific Treg and Breg may contribute to poor responses to vaccination. However, robust humoral and CMI responses to vaccination may result in increased circulating Treg and/or Breg, establishing a feed-back mechanism.


Asunto(s)
Linfocitos B Reguladores/inmunología , Infecciones por VIH/inmunología , Tolerancia Inmunológica , Subtipo H1N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Linfocitos T Reguladores/inmunología , Adolescente , Anticuerpos Antivirales/sangre , Niño , Preescolar , Ensayo de Immunospot Ligado a Enzimas , Femenino , Citometría de Flujo , Pruebas de Inhibición de Hemaglutinación , Humanos , Inmunofenotipificación , Vacunas contra la Influenza/administración & dosificación , Masculino , Adulto Joven
18.
J Am Geriatr Soc ; 58(9): 1734-8, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20863332

RESUMEN

OBJECTIVES: To provide pooled data on the prevalence of malnutrition in elderly people as evaluated using the Mini Nutritional Assessment (MNA). DESIGN: Retrospective pooled analysis of previously published datasets. SETTING: Hospital, rehabilitation, nursing home, community. PARTICIPANTS: Four thousand five hundred seven people (75.2% female) with a mean age of 82.3. MEASUREMENTS: The prevalence of malnutrition in the combined database and in the four settings was examined. RESULTS: Twenty-four data sets with information on full MNA classification from researchers from 12 countries were submitted. In the combined database, the prevalence of malnutrition was 22.8%, with considerable differences between the settings (rehabilitation, 50.5%; hospital, 38.7%; nursing home, 13.8%; community, 5.8%). In the combined database, the "at risk" group had a prevalence of 46.2%. Consequently, approximately two-thirds of study participants were at nutritional risk or malnourished. CONCLUSION: The MNA has gained worldwide acceptance and shows a high prevalence of malnutrition in different settings, except for the community. Because of its specific geriatric focus, the MNA should be recommended as the basis for nutritional evaluation in older people.


Asunto(s)
Evaluación Geriátrica/métodos , Desnutrición/epidemiología , Evaluación Nutricional , Vigilancia de la Población/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Casas de Salud , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiología
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