ABSTRACT
Vaccines are biological products that stimulate the immune system to generate specific responses and immune memory. Faced with the magnitude of the problem caused by the Covid-19 pandemic, there is an urgent need to find an effective and safe preventive intervention. The race to find the ideal vaccine against this new coronavirus has required optimizing research times on this topic. Currently, more than 200 SARS-CoV-2 vaccine candidates are in development, 177 in preclinical evaluation, 63 in clinical evaluation and 16 of them in phase 3 of clinical trials. In our country, 3 SARS-CoV-2 vaccines are already authorized for administration, which have demonstrated safety and efficacy in clinical trials. (AU)
Subject(s)
Humans , Male , Female , COVID-19 Vaccines/classification , COVID-19 Vaccines/therapeutic use , COVID-19 Vaccines/historyABSTRACT
Background: Transmitted drug resistance (TDR) occurs in patients with HIV infection who are not exposed to antiretroviral drugs but who are infected with a virus with mutations associated with resistance. Aim: To determine the prevalence of TDR and characterize HIV reverse transcriptase and protease mutation patterns. Material and Methods: HIV infected antiretroviral treatment-naive patients treated in three centers between 2014 and 2018 were studied. A genotyping study was carried out. The HIVdb Program (Stanford University) and the World Health Organization (WHO) TDR surveillance mutation list were used to register resistance-associated mutations. Results: We enrolled 220 patients aged a median of 29 (interquartile range (IQR) 24-34) years, 99% men. Median CD4 count was 365 cells/μL (IQR 250-499 cells/μL) and median viral load was 39.150 copies/mL (IQR 9,270 −120,000). The overall prevalence of RTD was 10.45% (95% CI 6.7-15.2, N = 23/220). The higher frequency of TDR was against non-nucleoside reverse transcriptase inhibitors, reaching 9.0% (95% CI 5.6-13.6), followed by nucleoside reverse transcriptase inhibitors reaching 1.8% (95% CI 0.49-4.5) and protease inhibitors reaching 0.45% (95% CI 0.01-2.5). The mutations in reverse transcriptase were M41L, L210W, D67N, K70E, M184V, K103N (6.36%, 95% CI 3.5-10.4), G190A, E138A, K101E, and I84V in protease. Conclusions: These results should prompt a change in recommendations for starting antiretoviral therapy, especially in first-line regimens that include non-nucleoside reverse transcriptase inhibitors.
Subject(s)
Aged , Female , Humans , Male , HIV Infections , HIV-1 , Anti-HIV Agents , HIV Infections/drug therapy , HIV Infections/epidemiology , Chile/epidemiology , Prevalence , HIV-1/genetics , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/pharmacology , Drug Resistance, Viral/genetics , Genotype , MutationABSTRACT
Resistance to anti-retroviral therapy is one of the main problems in the favorable outcome of treatment in HIV patients, as well as toxicity and adherence to treatment. Resistance has increased in recent years, and it is evaluated through genotyping and phenotypic tests. Information provided by these studies is crucial when deciding the most appropriate treatment. However, genotype interpretation is complex and subject to frequent change, because of the incorporation of new drugs and the appearance of new resistance patterns. This review aims ,understanding the fundamental concepts of antiretroviral resistance (ARV), which examines the general principles, mechanisms and patterns of resistance, both for the traditional family of anti-retrovirals, as well as for the most recently licensed drugs.
La resistencia a la terapia anti-retroviral constituye uno de los problemas fundamentales en el éxito del tratamiento, en los pacientes infectados con virus de la inmunodeficiencia humana, al igual que las toxicidades y los problemas de adherencia. La resistencia ha sido un problema creciente en los últimos años, y se estudia a través de pruebas genotípicas y fenotípicas. La información que proporcionan estos estudios, resulta una herramienta crucial en la clínica a la hora de instaurar el tratamiento más apropiado. Sin embargo, la interpretación del genotipo es compleja y está sujeta a cambios frecuentes, tanto por la incorporación de nuevos fármacos, como también por la actualización en los patrones de resistencia. Esta revisión tiene por objetivo, la comprensión de los aspectos fundamentales de la resistencia a los anti-retrovirales (ARVs), donde se analizan los principios generales, mecanismos y patrones de resistencia, tanto para las familias tradicionales de ARVs, como para las nuevas familias.
Subject(s)
Humans , Anti-HIV Agents/therapeutic use , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV-1 , Anti-HIV Agents/adverse effects , Genotype , HIV Infections/virology , HIV-1 , Mutation/geneticsABSTRACT
Background: The main cause of virological failure during AIDS treatment is the resistance to antiretroviral medications (ARV). Aim: To search for mutations associated with ARV resistance in recently HIV-1 infected patients naïve to treatment, in Chile. Material and Methods: Patients over 18 years old with HIV-1 infection, naïve to antiretroviral drugs before the study were included. Patients with CD4 cell counts less than 200 cells/mm³, viral load below 2.000 copies/mL or any condition indicative of advanced AIDS were excluded. Criteria for diagnosis of recent infection (< 18 months) were a previous negative test for HIV antibodies or a history of an acute retroviral syndrome in the past 18 months. Resistance to drugs was analyzed using the TRUGENEtm HIV-1 assay from Bayer and the OpenGene DNA sequencing system. Results: Ninety nine percent of patients had at least one mutation, 27 percent had 4 or more mutations, but high level resistance to ARV was found only in 2.7 percent of cases. Point mutations for non nucleoside reverse transcriptase inhibitors (NNRTI) were detected in 4.1 percent of cases (K103N in 1 patient, V179D in 2 patients), for nucleoside reverse transcriptase inhibitors (NRTI) in 8.1 percent of cases (T215S in 1 patient, V118I in 4 patients, M41L in 1 patient) and for protease inhibitors (PI) in 1.3 percent of cases. All mutations detected in the protease gene were secondary. Of these, the most common were L63P/T (38 patients), L10I/V (27 patients) and V77I (26 patients). Resistance to two or more antiretroviral classes was not detected. Conclusions: This study supports that, by now, primary resistance has a low prevalence in Chile. Therefore, a genotyping test before starting antiretroviral therapy is not necessary.
Subject(s)
Adolescent , Adult , Female , Humans , Male , Middle Aged , Young Adult , HIV-1 , Anti-HIV Agents/adverse effects , Drug Resistance, Viral/genetics , HIV Infections/drug therapy , Mutation/genetics , HIV-1 , Anti-HIV Agents/therapeutic use , Chile , HIV Infections/virology , Mutation/drug effectsABSTRACT
Background: Resistance limits the effectiveness of anti-retroviral therapy. In Chile, there is free access to highly active anti-retroviral therapy since 2001, but there is no information about the frequency of mutations associated to drug resistance. Aim: To determine the most common mutations associated to anti-retroviral drug resistance in Chile. Materials and Methods: Retrospective study of 710 genotype analysis coming from 568 patients aged 22 to 70 years (85 percent males) with virological failure. The analysis was performed using a commercially available sequencing kit (Trugene HIV-1 genotypic assay from Bayer S.A). Results: Mean CD4+ cell count and viral load were 154 cells/fil and 228784 RNA copies/ml, respectively. The frequency of resistance to nucleoside RT inhibitors (NRTI), non nucleoside RT inhibitors (NNRTI) and protease inhibitors (PI) was 71 percent, 62 percent and 22 percent, respectively. The most common mutations found were T215Y (46 percent), L10F (44 percent), Ml84V (3896), K103N (35 percent) and M41L (32 percent). Fifty five percent of mutations corresponded to the TAM (thymidine analogue mutations) group. Multiresistance was 47 percent to NNRTI, 7 percent to NRTI, 4 percent to PI and 0.7 percent to all groups. During the four years of the study, there was a significant increase in NNRTI resistance. Conclusions: These data provides important information about the epidemiology of drug resistance mutations and should help to design newHAARTstrategies.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , HIV-1 , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Drug Resistance, Multiple, Viral/genetics , HIV Infections/virology , Mutation/genetics , HIV-1 , Chile , Genotype , HIV Infections/drug therapy , Protease Inhibitors/therapeutic use , RNA, Viral/analysis , Retrospective Studies , Reverse Transcriptase Inhibitors/therapeutic use , Viral LoadABSTRACT
Las úlceras orales recurrentes (UOR), son lesiones inflamatorias frecuentes de la mucosa oral. Generalmente, son redondas u ovaladas, rodeadas por un halo eritematoso de fondo amarillo grisáceo y dolorosas en su mayoría. Las UOR alcanzan una frecuencia de hasta 20% en la población general, afectando a cualquier grupo etario, en especial a adolescentes y adultos jóvenes. La etiopatogenia de las UOR no está completamente dilucidada; algunos factores involucrados incluyen alteraciones inmunológicas, infecciones, déficit nutricional, traumas de la mucosa, alergia alimentaria y de contacto, enfermedades autoinmunes y neo-plasias; junto con factores psiquiátricos, genéticos y medioambientales. En el presente artículo se discuten las características clínicas, factores etiológicos, diagnósticos diferenciales y el estudio de las UOR.
Recurrent aphthous stomatitis (RAS), are common inflammatory lesions of the oral mucous, usually round or ovoid, circumscribed by an erytematous haloes with a yellow-grey floor and mostly painful. The RAS has reach an incidence about 20% in general population, present on any aged group, especially adolescents and young adults. Etiopathogenesis of RAS is not entirely understood. Some factors involved include immune system anomalies, infections, nutritional deficiency, mucous traumatism, food or contact allergy, autoimmunity illness and cancer; together with psychiatric, genetic and environment agents. In this article, main clinical features, etiology related factors, differential diagnosis and initial study of patients consulting for RAS are presented.
Subject(s)
Humans , Oral Ulcer , Diagnosis, Differential , Oral Ulcer/diagnosis , Oral Ulcer/etiology , Oral Ulcer/therapy , RecurrenceABSTRACT
Background: Highly active antiretroviral therapy (HAART) in HIV/AIDS infection induces an important reduction of the viral load (VL) and an immune system reconstitution. CD4+ T lymphocyte count is the immunological measurement commonly used for the follow up of HIV/AIDS patients. Aim: To study prospectively the restoration of the innate immune system in patients with HIV/AIDS infection during their first year on HAART. Patients and Methods: 25 naive HIV/AIDS patients, from San José Hospital and University of Chile Clinical Hospital, Santiago, Chile, were studied between years 2002-2003. Every 4 months after HAART initiation, CD3+, CD4+, CD8+ T lymphocytes and CD16/56+ natural killer (NK) cells were quantified by flow cytometry. NK cell cytotoxicity was measured using radioactive chrome liberation (Cr51). Tumor necrosis factor alpha (TNF-a) and interleukin-10 (IL-10) were measured in peripheral blood mononuclear cells and viral load was determined using Amplicor HIV-1 from Roche Diagnostics Systems. Results: Thirteen of the 25 patients continued in the study. They were all males, average age 35 years old (23-50). At baseline average CD4+ count was 146 cells/µL (31-362) and average viral load was 82.000 copies/mL (4.000-290.000). A raise in CD3+, CD4+, CD8+, and CD16/56 cells was noted at months 9-12 of therapy. Viral load became undetectable in the same period. NK cell function was decreased at the beginning of the therapy (1-4 months), reaching its highest values at months 9-12. There was no significant change in IL-10. TNF-a increased in six patients during the study. Conclusions: In this group of patients, innate immunity was restored during HAART. These results should be confirmed in studies with a longer follow up period and also measuring cytokines such as MIP-1a, MIP-1ß and RANTES.
Subject(s)
Adult , Humans , Male , Middle Aged , HIV-1 , Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , HIV Infections/immunology , Immunity, Innate , HIV-1 , Acquired Immunodeficiency Syndrome/drug therapy , Acquired Immunodeficiency Syndrome/immunology , Follow-Up Studies , HIV Protease Inhibitors/therapeutic use , /blood , Killer Cells, Natural/radiation effects , Prospective Studies , Reverse Transcriptase Inhibitors/therapeutic use , Time Factors , Tumor Necrosis Factor-alpha/blood , Viral LoadABSTRACT
Background: Resistance to antiretroviral therapy is a determining factor for therapeutic failure in HIV/AIDS. The prevalence of primary resistance (i.e. in those patients that have not received treatment) varies in different parts of the world. Aim: To study the prevalence of primary resistance to antiretroviral drugs in patients living in Northern Santiago. Patients and methods: Viral load, lymphocyte subpopulations by flow cytometry and genotypic resistance testing were assessed in blood samples from 60 HIV-1 infected patients (mean age 37 years, 54 male). Results: Mean CD4 cell count and viral load was 200 cells/ml and 142,840 RNA copies/ml respectively. Ten mutations were identified: V179D, L10I/V, M361, L63P, A71T/V, Y115F, V118I and K20R. None of these mutations is associated to a high degree of resistance to reverse transcriptase inhibitors, nucleoside analogs (NRTI), non nucleoside analogs (NNRTI) or viral protease inhibitors. Conclusions: This is a first approach to study antiretroviral resistance in Chilean patients. This study must be amplified, since the prevalence of resistance may experience changes with time.
Subject(s)
Male , Humans , Female , Middle Aged , HIV-1 , HIV Infections/drug therapy , Antiretroviral Therapy, Highly Active , Chile/epidemiology , MutationABSTRACT
La alergia a b-lactámicos es la primera causa de alergia medicamentosa en el mundo. En nuestro país, el estudio in vivo (pruebas cutááneas) realizado regularmente no se efectúa de acuerdo a patrones internacionales establecidos. Este artículo revisa el diagnóstico y manejo de estas reacciones. Las reacciones alérgicas a b-lactámicos pueden clasificarse, según su perfil temporal, en inmediatas, aceleradas y tardías, lo que se relaciona con las manifestaciones clínicas y mecanismos patogénicos. La mayor parte de las reacciones inmediatas y aceleradas son mediadas por IgE, con expresión clínica de hipersensibilidad inmediata. Entre las reacciones tardías destacan las toxidermias y exantemas máculo-papulares, mediadas probablemente por hipersensibilidad retardada. Los alergenos implicados en las reacciones de hipersensibilidad inmediata a b-lactámicos pueden ser los determinantes mayores (75 por ciento de los casos), determinantes menores o las cadenas laterales de los fármacos sospechosos. El estudio de estos pacientes incluye IgE específicas, pruebas cutáneas y pruebas de provocación. Los objetivos de estos estudios son diagnosticar reactividades cruzadas o monosensibilizaciones, y autorizar o prohibir la utilización de todos los b-lactámicos o sólo algunos de los fármacos del grupo, además de asegurar la tolerancia a fármacos alternativos.
Subject(s)
Humans , Anti-Bacterial Agents , Cross Reactions , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/epidemiology , Drug Hypersensitivity/therapy , Lactams/adverse effects , Lactams/immunology , Lactams/chemistry , Skin Tests/methods , Patch Tests/methods , Immunity, Cellular , Skin/pathology , Risk FactorsABSTRACT
Background: Esophageal candidiasis is associated with conditions that cause an immune depression. It is a defining disease for AIDS, is observed in poorly controlled diabetics, in patients with renal or hepatic failure, in patients with cancer and in subjects using medications causing immunosuppression or broad spectrum antimicrobials. Aim: To report the features of 10 immunocompetent patients with esophageal candidiasis. Patients and methods: Six males and four females aged between 48 and 82 years, without conditions associated with immunosuppression, in whom an esophageal candidiasis was found on an upper gastrointestinal endoscopy. Delayed skin hypersensitivity to eight antigens, Iymphocyte subpopulations, yeast phagocytosis and neutrophil chemotaxis were measured. Results: Six patients had a low CD4 Iymphocyte count and seven had a low CD8 count. Seven patients were anergic on skin hypersensitivity challenge. Yeast phagocytosis was abnormal in one patient and neutrophil chemotaxis was abnormal in two. Humoral immunity was normal in all subjects. All patients were treated with oral fluconazole in doses of 150 mg/day for 14 days, with complete resolution of candidiasis in all. Conclusions: Patients with esophageal candidiasis, have frequent alterations of cellular immunity, that must be diagnosed and treated.