ABSTRACT
Abstract: The adverse effects of oral pre-exposure prophylaxis (PrEP) using tenofovir disoproxil fumarate are barriers to PrEP initiation and continuation. Although serious effects are rare and predictable, evidence for this assessment among men who have sex with men (MSM) and transgender women (TGW) is still limited. This study assesses the adverse effects of daily oral PrEP in MSM and TGW. This is a systematic review and meta-analysis of clinical trials and cohort studies on the use of daily oral PrEP selected from the PubMed/MEDLINE, Embase, LILACS, and Cochrane CENTRAL databases. Data extraction included adverse effects and changes in renal and hepatic markers. Random effects models were used to summarize the risk of adverse effects throughout the study. Heterogeneity was assessed using the Cochran's Q test and the inconsistency test (I2). The risk of bias and the certainty of the evidence were assessed using the Cochrane Collaboration recommendations. The search identified 653 references. Of these, 10 were selected. All studies assessed the eligibility of renal and hepatic markers. The use of daily oral PrEP was not associated with grade 3 or 4 adverse events (RR = 0.99; 95%CI: 0.83-1.18; I2 = 26.1%), any serious adverse event (RR = 1.04; 95%CI: 0.58-1.87; I2 = 88.4%), grade 3+4 creatinine level (RR = 0.66; 95%CI: 0.24-1.84; I2 = 79.9%), and grade 3 or 4 hypophosphatemia (RR = 0.56; 95%CI: 0.15-2.10). The certainty of the evidence ranged from high to moderate for the outcomes analyzed. Daily oral PrEP is safe and well tolerated by MSM and TGW. Adverse effects were minimal and evenly distributed between intervention and control.
Resumo: Os efeitos adversos da profilaxia pré-exposição (PrEP) oral com fumarato de tenofovir desoproxila são barreiras para o início e a continuidade da PrEP. Embora os efeitos graves sejam raros e previsíveis, as evidências dessa avaliação entre homens que fazem sexo com homens (HSH) e mulheres transgênero (MTG) ainda são limitadas. Este estudo avalia os efeitos adversos da PrEP oral diária em HSH e MTG. Trata-se de uma revisão sistemática e metanálise de ensaios clínicos e coortes que demonstram o uso de PrEP oral diária selecionados nas bases de dados PubMed/MEDLINE, Embase, LILACS e Cochrane CENTRAL. A extração de dados incluiu os efeitos adversos e alterações nos marcadores renais e hepáticos. Modelos de efeitos aleatórios foram usados para resumir o risco de efeitos adversos ao longo do estudo. A heterogeneidade foi avaliada pelo teste Q de Cochran e inconsistência (I2). O risco de viés e a certeza da evidência foram avaliados por meio das recomendações da Colaboração Cochrane. Foram identificadas 653 referências. Destes, dez foram selecionadas. Todos os estudos avaliaram marcadores renais de elegibilidade e marcadores hepáticos. O uso diário de PrEP oral não foi associado a eventos de grau 3 ou 4 (RR = 0,99; IC95%: 0,83-1,18; I2 = 26,1%), a qualquer evento adverso grave (RR = 1,04; IC95%: 0,58-1,87; I2 =88,4%), à creatinina grau 3 ou 4 (RR = 0,66; IC95%: 0,24-1,84; I2 = 79,9%) e à hipofosfatemia grau 3 ou 4 (RR = 0,56; IC95%: 0,15-2,10). A certeza das evidências variou de alta a moderada para os desfechos analisados. A PrEP oral diária é segura e bem tolerada por HSH e MTG. Os efeitos adversos foram mínimos e distribuídos uniformemente entre a intervenção e o controle.
Resumen: Los efectos adversos de la profilaxis preexposición (PrEP) oral con fumarato de disoproxilo de tenofovir son barreras para el inicio y la continuación de la PrEP. Aunque los efectos graves son raros y predecibles, la evidencia de esta evaluación entre hombres que tienen sexo con hombres (HSH) y mujeres transgénero (MTG) sigue siendo limitada. Este estudio evalúa los efectos adversos de la PrEP oral diaria en HSH y MTG. Se trata de una revisión sistemática y un metaanálisis de ensayos clínicos y cohortes que demuestran el uso de la PrEP oral diaria seleccionada de las bases de datos PubMed/MEDLINE, Embase, LILACS y Cochrane CENTRAL. La recolección de datos incluyó efectos adversos y cambios en los marcadores renales y hepáticos. Se utilizaron modelos de efectos aleatorios para resumir el riesgo de efectos adversos a lo largo del estudio. La heterogeneidad se evaluó mediante la prueba Q de Cochran y la inconsistencia (I2). El riesgo de sesgo y la certeza de la evidencia se evaluaron utilizando las recomendaciones de la Colaboración Cochrane. Se identificaron 653 referencias. De estas, se seleccionaron diez. Todos los estudios evaluaron los marcadores renales de elegibilidad y los marcadores hepáticos. El uso diario de la PrEP oral no se asoció con eventos de grado 3 o 4 (RR = 0,99; IC95%: 0,83-1,18; I2 = 26,1%), con ningún evento adverso grave (RR = 1,04; IC95%: 0,58-1,87; I2 = 88,4%), con creatinina de grado 3 o 4 (RR = 0,66; IC95%: 0,24-1,84; I2 = 79,9%) y con hipofosfatemia de grado 3 o 4 (RR = 0,56, IC95%: 0,15-2,10). La certeza de la evidencia varió de alta a moderada para los resultados analizados. La PrEP oral diaria es segura y bien tolerada por HSH y MTG. Los efectos adversos fueron mínimos y se distribuyeron uniformemente entre la intervención y el control.
ABSTRACT
Objective@#To explore the efficacy of a combination regimen by Lopinave/Litonawe (LPV/r), emtricitabine and tenofovir alafenamide fumarate (FTC/TAF) for the treatment of novel coronavirus pneumonia (NCP).@*Methods@#We design the protocol as a real world study, which includes two groups: prospective intervention cohort (T1) and historical control group (T2). For T1 group, ninety patients will be enrolled who are diagnosed as NCP. All patients in T1 group will receive standard therapies following the recommendation in the guidelines of National Commission of Health, and they will be administered an anti-virus regimen includes LPV/r and FTC/TAF. The T2 group will enroll patients who have received single regimen includes LPV/r. The major outcome is the survival rate of patients. Secondary outcomes are the time of seroconversion of RNA, ARDS progression rate and length of hospital stay.@*Conclusions@#The results of this real world study might provide clinical practitioners a high efficiency and fast antivirus regimen for NCP. In addition, the conduction of this study will accelerate screening for other new effective therapeutic method.
ABSTRACT
Abstract: A simple, rapid, accurate and economical method has been developed for thesimultaneous estimation of Emtricitabine and Tenofovir Alafenamide in tablet dosage form.The linearity of the method was found to be in the range of 10.8µg/ml- 12.8µg/ml forTenofovir Alafenamide and 86.4µg/ml-102.4µg/ml for Emtricitabine. From the developedmethod the drugs showed maximum absorbance at 263 and 281nm for Tenofovir Alafenamideand Emtricitabine respectively. The percentage purity of the drugs was found as 96.8 and97.6%w/w for Tenofovir Alafenamide and Emtricitabine respectively. The method was alsofound to be accurate, precise, robust and rugged. The limit of detection and the limit ofquantification were found to be 0.234µg/ml and 0.710µg/ml for Tenofovir Alafenamide and2.25µg/ml and 6.83µg/ml for Emtricitabine respectively..
ABSTRACT
Abstract Introduction: Initial treatment of the HIV is based on the use of three drugs, two of which are nucleoside analog reverse-transcriptase inhibitors. There are three combinations of these drugs which have been approved by different guidelines, each with divergent results in terms of efficacy and safety. Objective: To compare the efficacy and safety of these three combinations. Methods: Systematic review and network meta-analysis of randomized clinical trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC). Results: Seven clinical trials met the eligibility criteria. The results suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at 48 weeks. However, there is clinical and statistical heterogeneity. Subgroup analysis were performed by third drug and by level of viral load prior to treatment, and found no differences in virological control. Network meta-analysis could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of patients with virological response, with no differences at 48 weeks nor at 96 weeks. Direct comparisons showed an increased risk of bone marrow suppression of ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC Conclusions: The results did not show differences in effectiveness among the interventions. However, due to the heterogeneity of the third drug and the follow-up time between the included studies, this result is not definitive. The results raise the need for further studies to help improve treatment recommendations in patients infected with HIV.
Resumen Introducción: El tratamiento inicial de la infección por VIH se basa en el uso de tres medicamentos, dos de ellos inhibidores de transcriptasa reversa análogos de nucleósido. Existen tres combinaciones de estos medicamentos aprobadas por diferentes guías, con resultados divergentes en cuanto a eficacia y seguridad. Objetivo: Comparar la eficacia y seguridad de las 3 combinaciones Métodos: Revisión sistemática y metanálisis en red de ensayos clínicos con asignación aleatoria comparando dosis fijas de Tenofovir Disoproxil Fumarato/Emtricitabina (TDF/FTC), Abacavir/Lamivudina (ABC/3TC) y Zidovudina/Lamivudina (ZDV/3TC). Resultados: Siete ensayos clínicos cumplieron los criterios de elegibilidad. Los resultados sugirieron mayor eficacia con TDF/FTC vs ABC/3TC a 96 semanas y vs. ZDV/3TC a 48 semanas. Sin embargo, existe heterogeneidad clínica y estadística. Se realizó análisis de subgrupos por tercer medicamento y por nivel de carga viral previa al tratamiento, sin encontrar diferencias en control virológico. Se pudo realizar metanálisis en red con TDF/FTC vs ZDV/3TC y proporción de pacientes con respuesta virológica, sin diferencias a las 48 semanas ni 96 semanas. Las comparaciones directas evidenciaron mayor riesgo de supresión de médula ósea de ZDV/3TC vs TDF/FTC y de reacciones de hipersensibilidad de ABC/3TC vs ZDV/3TC. Conclusión: Los resultados no demostraron diferencias en efectividad entre las intervenciones; sin embargo, debido a heterogeneidad en cuanto al tercer medicamento y el tiempo de seguimiento entre los estudios incluidos, dicho resultado no es definitivo. Los resultados plantean la necesidad de realizar nuevos estudios que ayuden a mejorar las recomendaciones de tratamiento en los pacientes infectados por el VIH.
Subject(s)
Humans , HIV Infections/drug therapy , Anti-HIV Agents/administration & dosage , Dideoxynucleosides/administration & dosage , Dideoxynucleosides/adverse effects , Zidovudine/administration & dosage , Zidovudine/adverse effects , Randomized Controlled Trials as Topic , Treatment Outcome , Lamivudine/administration & dosage , Lamivudine/adverse effects , Anti-HIV Agents/adverse effects , Drug Combinations , Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination/administration & dosage , Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination/adverse effects , Network Meta-AnalysisABSTRACT
Stribild is a compound preparation composed of elvitegravir, cobicistat, emtricitabine and tenofovir. As for the first-treated AIDs patients or re-treated patients with creatinine clearance≥70ml·min-1 , it has definite clinical effect. Owing to once a day, stribild can enhance the acceptability of the patients, and as for the patients treated with other regimen complicated with diarrhea, pain in stomach and numbness in hands and feet, it also provides a good option. However, its adverse effects on kidney, liver and bone density in the long term use should be paid attention.
ABSTRACT
The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) were analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naïve and ART-experienced Asian subjects infected with human immunodeficiency virus (HIV)-1. Studies GS-US-236-102 and GS-US-236-103 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naïve subjects, comparing E/C/F/TDF versus efavirenz (EFV)/F/TDF or ritonavir-boosted atazanavir (ATV+RTV) plus emtricitabine/tenofovir DF (F/TDF), respectively. Studies GS-US-236-115 and GS-US-236-121 were randomized, open-label, 96-week long conducted in ART-experienced subjects, who switched to E/C/F/TDF from ritonavir-boosted protease inhibitors (PI+RTV)+F/TDF, or non-nucleoside reverse transcriptase inhibitors (NNRTI)+F/TDF regimens. The E/C/F/TDF appeared to have sustained efficacy and safety and was well tolerated in the small number of ART-naïve and ART-experienced Asian subjects.
Subject(s)
Humans , Humans , Asian People , Atazanavir Sulfate , HIV , HIV-1 , Protease Inhibitors , Reverse Transcriptase InhibitorsABSTRACT
A rapid, economic and robust stability indicating HPLC method was developed and validated to quantify Tenofovir disoproxil Fumarate (TDF), Emtricitabine (EMT) and Nevirapine (NVP) simultaneously at single wavelength (254 nm) in order to assess the in vitro drug release profile from tablet formulations. Chromatographic separation was performed with a gradient elution of samples on a 4.6 mm x 150 mm, 5 μm, Inertsil ODS-2 column with buffered mobile phase containing solvent A (10 Mm ammonium acetate buffer, pH 4.6) and solvent B ( acetonitrile) at a flow rate of 1.0 mL/min). In dissolution studies, the sink condition was optimized based on quantitative solubility of TDF, EMT and NVP standards in different dissolution medium as recommended by USP. The proposed HPLC method and dissolution test condition were validated as per ICH guidelines. The results obtained meet the regulatory criteria thereby confirming that the method is suitable for routine quality control analysis and in vitro dissolution studies.
ABSTRACT
Human Immunodeficiency Virus (HIV) epidemic continues to represent a major global health issue. Today, there are several tools available to prevent the spread of HIV infection. However, there are several constraints to the current prevention strategies including low condom use, low acceptance of testing, low awareness of vulnerability and more emphasis on treatment. Prevention strategy is redirected towards reducing acquisition of HIV. Pre-exposure prophylaxis or PrEP is the latest groundbreaking innovation in biomedical research in the prevention of HIV transmission. The purpose of this paper is to review preexposure prophylaxis for HIV prevention including the current guidelines in the use of PreP.
El virus de la Inmunodeficiencia Humana (VIH) continúa representando un importante problema de salud mundial. Hoy en día, existen varias herramientas disponibles para evitar la propagación de la infección por el VIH. Sin embargo, existen varias restricciones a las estrategias de prevención actuales, incluyendo el bajo uso del condón, baja aceptación de la prueba, la escasa conciencia de la vulnerabilidad y un mayor énfasis en el tratamiento. La estrategia de prevención se redirige hacia la reducción de la transmisión del VIH. La profilaxis pre-exposición o "PrEP" es la última innovación pionera en la investigación biomédica en la prevención de la transmisión del VIH. El propósito de este trabajo fue revisar la profilaxis de pre-exposición para la prevención del VIH, incluyendo las directrices actuales en el uso de PrEP.
Subject(s)
Humans , HIV , Disease Prevention , AIDS SerodiagnosisABSTRACT
El tratamiento de hepatitis B está en fase de experimentación en espera de obtener medicamentos con mayor eficiencia y menor resistencia. La mayoría de los medicamentos, en experimentación, son análogos de nucleósidos y nucleóticos que inhiben competitivamente la polimerasa HBV. La emtricitrabina es un medicamento que potencialmente se podría utilizar en pacientes coinfectados con HIV con el inconveniente de la resistencia cruzada a lamivudina. El tenofovir es un medicamento prometedor en los pacientes coinfectados con HIV tanto los Hbe Ag negativo como los resistentes a lamivudina. Prodrogas como el pradefovir se visualizan como medicamentos más efectivos y con menos efectos adversos que la droga original. La mayoría de estos medicamentos requieren de más estudios para definir su rol en el tratamiento de la hepatitis B crónica.
Hepatitis B treatment is in the experimentation stage expecting to obtain more effective and less resistant treatments. Most treatments under experimentation are nucleoside and nucleotide analogues that competitively inhibit HBV polymerase. Emtricitabine is a drug that could be used in con-infected HIV patients with the inconvenience of cross-resistance to lamivudine. Tenofovir is a promising drug for co-infected HIV patients, not only for the HbeAg negative but also for those resistant to lamuvidine. Pro-drugs such as pradefovir are considered more effective and with less adverse effects than the original drug. Most of these drugs require more studies to define its role in the treatment of chronic hepatitis B.