Spelling suggestions: "subject:"antiretroviral"" "subject:"antirretroviral""
11 |
Mechanisms underlying reductions in mother-to-child transmission of human immunodeficiency virus type-1 by short-course antiretroviralsSchramm, Diana Bettina 14 February 2007 (has links)
Student Number : 8044255 -
PhD thesis -
School of Pathology; Discipline Virology -
Faculty of Health Sciences / Knowledge of the timing of mother-to-child transmission (MTCT) of HIV-1 is an important issue in reducing the risk of infant infection. Prior to giving birth therefore an HIV-1 positive mother should be provided with anti-HIV-1 drugs (antiretrovirals) during the shortest time possible to ensure both efficacy and minimal toxicity of the antiretrovirals to the newborn. However, in the absence of timeous administration of nevirapine (NVP) or zidovudine (AZT) to the mother at the onset of labour, infants are given post-exposure prophylaxis (PEP). Despite antiviral prophylaxis some infants still become infected. In an attempt to mimic the in vivo scenario we investigated, in Chapter Three, the replication ability of a primary isolate (M502L) in peripheral blood mononuclear cells (PBMC) isolated from healthy donors exposed to different concentrations of NVP or AZT either prior to or post-infection, but that reflected mean neonatal plasma concentrations measured following maternal dosing. In phytohaemagglutinin (PHA) stimulated cultures M502L exhibited some growth. Maintaining NVP and AZT in the culture medium resulted in decreased viral growth over time. In contrast to that expected certain donors demonstrated elevated p24 antigen levels in the presence of HIV-1 and NVP or AZT. This suggested that cells were more conducive to HIV-1 replication either because of cellular activation or due to cellular production of cytokines/chemokines. The in vitro study highlighted (i) the differential permissiveness of cells from different donors for HIV-1 infection, (ii) different abilities of antiretrovirals (ART) to circumvent infection in different individuals and (iii) immunomodulatory effects of ART in vitro.
Commencing in Chapter Four we elected to investigate, in vivo, the immunomodulatory consequences of HIV-1 exposure and infection in two groups of HIV-1-exposed newborns whose mothers either received NVP at the onset of labour or who only received NVP as PEP within 72 hours of birth. Short-course antiretroviral drug regimens are known to reduce the risk of MTCT of HIV-1 but mechanisms affording protection of such interventions remain poorly defined. Since T-cell activation is an important factor in productive HIV-1 infection, we tested the hypothesis that single-dose NVP reduces immune activation, which in turn reduces the likelihood of transmission. We compared concentrations of cord and maternal blood plasma immune activation markers, neopterin, β2-microglobulin (β2-m) and soluble L-selectin (sL-selectin) in the two groups of HIV-1-exposed newborns and among HIV-unexposed controls. In utero exposure of the infant to HIV-1, regardless of NVP exposure, led to demonstrable increases in levels of immune activation markers, this being most notable in the presence of pre-existing infection. Contrary to what was hypothesized, immune activation was increased by pre-birth exposure to single-dose NVP, with this effect being enhanced in infants already infected at birth. Our data suggest that reductions in immune activation do not explain transmission prevention effects of single-dose NVP. Our data also suggest a biological explanation for why HIV-1 infected infants exposed perinatally to antiretroviral drugs might experience hastened disease progression, namely that the immunological mileau in some HIV-1 infected individuals treated with NVP favours increased HIV-1 replication.
Cytokines and chemokines function to stimulate, or suppress cellular proliferation and differentiation and have unique immunomodulatory properties. Furthermore, they have the potential to protect against HIV-1 infection or to regulate HIV-1 replication. In Chapter Five we therefore questioned whether exposure to HIV-1 or NVP influences cytokine/chemokine levels of infants born to HIV-1 infected mothers. We compared levels of interleukin (IL)-7, IL-10, stromal cell-derived factor: SDF-1α (CXCL12), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage inflammatory protein-1α: MIP-1α (CCL3), macrophage inflammatory protein-1β: MIP-1β (CCL4) and regulated upon activation, normal T-cell expressed and secreted: RANTES (CCL5) of the two groups of HIV-1-exposed newborns and among the HIV-unexposed controls. HIV-1 exposure in the absence of single-dose NVP was not found to impact significantly on the levels of IL-7, IL-10, GM-CSF, CXCL12, CCL3, CCL4 or CCL5 and single-dose NVP had no appreciable effect on these cytokine/chemokine levels. Cord blood plasma levels of IL-7, CXCL12 and GM-CSF were found to be independent of mothers’ levels. Single-dose NVP reduced the ability of cord blood mononuclear cell (CBMC) to produce GM-CSF spontaneously. Maternal and infant (HIV-1 exposed NVP unexposed) IL-10 levels were significantly correlated. Significantly elevated levels of IL-10 were associated with pre-existing infection in NVP unexposed newborns. CCL3, CCL4 and CCL5 levels in NVP unexposed uninfected infants were not different from those of control infants but correlated significantly with IL-7 levels.
HIV-1 specific cellular immune responses are elicited in a proportion of infants born to HIV-1 seropositive mothers and have been associated with protection from maternal HIV-1 transmission. In Chapter Six, levels of the immune activation markers neopterin, β2-m, sL-selectin, the immunomodulatory and haematopoietic factors IL-7, CXCL12, GM-CSF and the immunoregulatory cytokine IL-10 were examined amongst the group of newborns, that received NVP as PEP within 72 hours of birth, of which a proportion had specific cellular responses to HIV-1 envelope (Env) peptides. It was our aim to determine in infants that elicit HIV-1 specific cellular immune responses (Env+) and those that lack the specific responses (Env-), whether these factors could predict transmission and whether the former group of infants exhibit unique immune features that might distinguish them from Env- non-responders. Our data suggested that none of the factors tested were predictive of HIV-1 transmission but confirmed that infants with cellular responses to HIV-1 envelope peptides were associated with lack of subsequent infection. In particular, our data demonstrated an association between HIV-1 specific cellular immune responses, lower maternal viral load and lack of infection suggesting that sustained exposure to antigen (reduced maternal viral load) may be responsible for the strong priming effect. Furthermore, an association between reduced GM-CSF levels and the presence of HIV-1 specific responses was demonstrated, which suggested therefore that newborn infants that elicited HIV-1 specific cellular immune responses exhibited different immune capabilities from those without responses.
Finally, in Chapter Seven we looked at how immune activation and priming impact on thymic output of T-cells in newborn infants. Unfortunately, sample volumes of the two groups of HIV-1-exposed newborns used in the previous three Chapters became limited with the result that we chose to address these questions using anonymously collected cord blood samples from infants, some of which were used to supplement the placebo group of the the UNAIDS-sponsored clinical trial of short-course zidovudine-lamivudine (AZT-3TC). At the time the AZT-3TC trial was conducted short-course antiviral prophlyaxis was not the standard of care for the prevention of MTCT of HIV-1. The thymus is known to be essential for establishing diversity of the T-cell pool, and morphological thymic changes and effects on naïve T-cells and T-cell receptor excision circle (TREC) concentrations have been reported in studies of HIV-1 infected children and adults. As it is not known to what extent in utero exposure to HIV-1 and infection affects T-cell division in newborn infants, we elected to determine TREC levels of infants born to HIV-1 seropositive mothers that were not exposed to antiretrovirals. The impact of increased immune activation on TREC levels and the consequence of HIV-1 exposure or infection on circulating levels of IL-7 (raised levels indicative of T-cell depletion) was also investigated. HIV-1 exposure or infection did not result in significant losses of TREC. TREC levels were not affected by immune activation associated with HIV-1 exposure and infection and IL-7 levels were not raised. Infants that elicited HIV-1 specific cellular immune responses exhibit TREC levels that were similar to those of infants without HIV-1 specific responses. These data suggested that newborn infants of HIV-1 seropositive mothers demonstrated no altered thymopoietic ability compared to control infants. Furthermore, HIV-1 specific immune responses, (indicative of post-thymic memory T-cell expansion) did not influence thymic output measured in newborn infants.
In conclusion, the in vitro study demonstrated that there is a high degree of variability between PBMC isolated from different donors with respect to viral replication and drug effectivity which suggests that these phenomena are likely to exist within patient (infant as well as adult) populations. While immune activation is considered central to productive infection we demonstrated that immune activation is increased by HIV-1 exposure and by single-dose NVP. Exposure to HIV-1 alone or with NVP did not influence birth levels of IL-7, IL-10, CXCL12, GM-CSF, CCL3, CCL4 and CCL5. Furthermore, levels of these factors did not predict infection outcome in the infant. Immune activation and haematopoietic growth factors are modulated independently of the mother but maternal factors such as IL-10 and exposure to single-dose NVP, which reduces responsiveness of CBMC, could impact on the infant. HIV-1 specific cellular immune responses at birth, which are elicited in a proportion of infants born to HIV-1 positive mothers, are of immunological significance and can predict lack of subsequent infection. Disturbances in thymic output are not readily detectable at birth when using TREC to assess de novo T-cell synthesis, alternatively there is a homeostatic balance between thymic output and peripheral T-cell proliferation in newborns of HIV-1 infected mothers. Overall our data suggests that (i) there are immune consequences of being born to an HIV-1 positive mother, (ii) short-course antiretroviral prophylaxis does impact on the developing immune system of the infant and (iii) while the direct effects of single-dose NVP are not disputed, there are indirect consequences of NVP exposure on immune cells. Despite the consequences of HIV-1 exposure or the result of being born to a HIV-1 seropositive mother or exposure to single-dose NVP, our data proposes that the immune system of newborn infants is capable of responding as demonstrated by the enhanced immune activation. It remains important to determine the correlates of immune protection for the development of novel immuno-therapeutic and vaccine strategies and maternal-infant transmission of HIV-1 provides a model which can address questions of protective immune processes. Understanding the influence of antiretrovirals on immune processes remains an important component of the drug mechanisms, (aside from their direct antiretroviral activity), that may underlie reductions in maternal-infant transmission of HIV-1. Furthermore, how antiretrovirals influence immune processes and immune development (together with exposure to HIV-1/consequences of being born to an HIV-1 seropositive mother), may impact on subsequent immune responsiveness to infectious organisms or childhood vaccines.
|
12 |
Avaliação in vitro da solubilidade e da permeabilidade da lamivudina e da zidovudina. Aplicações na classificação biofarmacêutica / Solubility and permeability evaluation of lamivudine and zidovudine. Biopharmaceutical classification.Dezani, Andre Bersani 21 October 2010 (has links)
A biodisponibilidade é o fator determinante da eficácia clínica de um fármaco e depende diretamente das propriedades de solubilidade e permeabilidade da substância ativa. O Sistema de Classificação Biofarmacêutica (SCB), baseado nestas características, consolidou-se nos últimos anos como ferramenta de auxílio na predição da biodisponibilidade de fármacos. O SCB tem sido empregado no desenvolvimento de formas farmacêuticas, contendo novos fármacos ou não, e no registro de medicamentos genéricos, por conta das limitações técnicas, econômicas e éticas para a realização dos ensaios diretos de biodisponibilidade. Assim, a avaliação das propriedades de solubilidade e permeabilidade dos fármacos, embora indiretamente, oferece objetivas indicações sobre a eficácia dos medicamentos, com vantagem de consolidar modelos in vitro, mais facilmente reprodutíveis, sem trazer riscos a voluntários sadios. Dentre os estudos de solubilidade destaca-se o método do equilíbrio que emprega a técnica de shake-flask. Para a determinação da permeabilidade in vitro, diferentes técnicas têm sido empregadas, dentre as quais destacam-se modelos que empregam tecido intestinal de animais. O presente trabalho teve como objetivos a avaliação da solubilidade e da permeabilidade de fármacos antirretrovirais (lamivudina e zidovudina) e o desenvolvimento de protocolo para determinação da permeabilidade em segmentos de intestino de ratos, por meio de modelo in vitro em ensaios com células de Franz. A solubilidade dos fármacos propostos foi caracterizada pela técnica shake-flask e por meio da dissolução intrínseca, sendo que os resultados permitiram concluir que, segundo o SCB, os fármacos zidovudina e lamivudina apresentam alta solubilidade. Os ensaios de permeabilidade demonstram que o método proposto é viável e os valores de permeabilidade da lamivudina e da zidovudina sugerem que ambos os fármacos podem ser classificados como de alta permeabilidade. / Bioavailability is the determinant of the clinical efficacy of a drug and is directly dependent on the properties of solubility and permeability of the active substance. The Biopharmaceutical Classification System (BCS), based on these characteristics, has become in recent years as a tool to aid in predicting the bioavailability of drugs. The BCS has been used in the development of dosage forms, containing new drugs or not, and the registration of generic drugs, since there are technical limitations, economic and ethical guidelines for the testing of direct bioavailability. Thus, the evaluation of the solubility and permeability of the drugs, although indirectly, provides objective indications on the effectiveness of medicines, with the advantages of consolidating in vitro models more easily reproducible without bringing risk to healthy volunteers. Among the solubility studies highlight the shake-flask method, recommended by regulatory agencies. To determine the in vitro permeability, different techniques have been employed, among which stand out models based on intestinal tissue obtained from different animals. This study aims to evaluate the solubility and permeability of antiretroviral drugs (lamivudine and zidovudine), and the development of protocol for the determination of permeability in intestine segments of rats using in vitro model in experimental Franz cells. So far, the solubility of proposed drugs was characterized by shake-flask method and through the intrinsic dissolution. About the solubility, results showed that, according to BCS, the drugs zidovudine and lamivudine has high solubility. About the intrinsic dissolution, results showed agreement with the results of the solubility. Permeability tests showed that the proposed method is feasible and the permeability values of lamivudine and zidovudine suggest that both drugs can be classified as high permeability.
|
13 |
Collaborative and partnership opportunities in the area of research and development for paediatric antiretroviral drugs for low income countriesMartin, Gregory 28 June 2011 (has links)
This research was motivated by the urgent need for global health institutions like the World Health Organization and UNITAID to adopt an informed, market based approach to engaging with the research and development pipeline for drugs that treat children infected with the HIV virus. As the market size for these products declines over the next decade, the usual incentives for pharmaceutical and biotech companies to invest in the development of new drugs and new formulations of existing drugs is likely to dwindle. Innovated solutions are needed if a business case is to be made that addresses this important public health need. The objectives of the research include firstly, describing the public health need for research and development into paediatric Antiretroviral drugs; secondly describing the various stakeholders and their interests; and finally exploring and indentifying potential collaborative / partnership opportunities that can be employed to address the existing public health need while satisfying the various stakeholder interests at play.
|
14 |
The role of family support and HIV/AIDS stigma on adherence and non-adherence to antiretrovirals at Nzhelele in Limpopo Province, South AfricaMathivha, Tshifularo Maud January 2012 (has links)
Thesis (M.PH.) --University of Limpopo, 2012 / Objectives: To determine the level of adherence of people who are on ARVs
and to determine the influence of HIV and AIDS stigma and family support on adherence and non-adherence to antiretrovirals.
Methods: A descriptive cross sectional study involving 175 HIV/AIDS adult patients attending Siloam hospital was conducted. These patients were on ARV drugs. They were investigated for the level of adherence and the influence of HIV and AIDS stigma and family support on adherence and non-adherence to antiretrovirals. Data were collected from respondents through self-administered questionnaires which were distributed to 175 randomly selected participants. The key variables were demographic information and social support and disclosure, current use of ARVs and personal experience of living with HIV/AIDS. Data were analyzed using descriptive statistics, numerical summaries, tables, graphs, ANOVA, Pearson chi-square test and statistical package for social sciences (SPSS).
Results: Forty comma eight percent (40,8%) of the respondents on ARVs were males and 28, 8 % females aged between 23-35 years; 23, 9% males and 40, 4% females ranged between 36-45 years; 35, 2% males and 30, 8% were 46 years old and above. The most commonly cited reasons for missing doses were: Social grant, forgetting, side effects and stigma. The most cited reasons for taking medication were: respondents wanted to feel better; to increase the CD4 count; and they feared death. The majority of the adhering participants, 68, 9% and 55, 8% of the non- adhering group never experienced negative reactions from their families after disclosure. There was no significant difference between the adhering and the non adhering group (P =0.250). A substantial number of ARV users of the adhering group 92, 2% participants disclosed that they were receiving support which included emotional/psychological support, financial support, physical care support as well as reminders to ensure that they took their medications on time. There was no significant difference between the adhering and the non adhering group on the general satisfaction with the overall support they received from their family (p= 0.976).
Conclusion: Patients have a range of reasons for failing to adhere to their antiretroviral therapy and reasons for adhering. Support can improve adherence to therapy and patients can only receive support if they revealed their HIV positive status. It was recommended that the community should be sensitised about the availability of treatment and the importance of adherence
Keywords: Adherence, antiretrovirals, HIV/AIDS, stigma and family support
|
15 |
Perfil de resistência genótica do HIV-1 em pacientes com falha na terapia antirretroviral atendidos pela Rede Nacional de Genotipagem (RENAGENO) na região de Botucatu, SP-Brasil /Munhoz, Lilian da Silva Reis. January 2011 (has links)
Resumo: Os antirretrovirais (ARVs) interferem nas enzimas virais resultando na inibição da replicação do HIV. O uso combinado destas drogas tem demonstrado grande eficácia no controle da progressão da infecção pelo HIV e aumento da sobrevida do paciente. Entretanto estes benefícios podem ser comprometidos pelo desenvolvimento de resistência às drogas, consequência da emergência de mutações nas enzimas virais, representando um grande obstáculo para o sucesso do tratamento de pacientes infectados pelo HIV-1. Os testes de resistência, principalmente de genotipagem do HIV-1, permitem a orientação de novos esquemas, possibilitando o retorno da supressão viral. Este estudo teve como objetivo avaliar o perfil de mutações e a resistência genotípica aos Inibidores da Transcriptase Reversa análogos de Nucleosídeos (ITRN), Inibidores da Transcriptase Reversa Não-análogos de Nucleosídeos (ITRNN) e Inibidores da Protease (IP) em pacientes com falha terapêutica submetidos ao exame de genotipagem, realizado no Laboratório de Rotinas Diagnósticas em Biologia Molecular do Hemocentro da FMB - UNESP ponto executor da RENAGENO (Rede Nacional de Genotipagem do HIV-1). Foram analisadas sequências genômicas da região pol do HIV-1 provenientes de todos os pacientes com exame de genotipagem realizados durante os anos de 2008 e 2009. Dois grupos distintos foram formados: grupo "Adulto" (idade ≥ 18 anos), com 386 indivíduos, e grupo "Pediátrico" (<18 anos), com 45 pacientes, totalizando 431 pacientes. A genotipagem foi realizada pelo kit comercial Trugene HIV-1 Genotyping Kit (Siemens Healthcare Diagnostics). As sequências obtidas foram submetidas ao Algoritmo de Interpretação de Resistência Genotípica da Universidade de Stanford (HIVdb) e a subtipagem foi realizado pelo REGA HIV-1 Subtyping Tool e pelo programa RIP 3.0. O subtipo B foi o mais frequente nos dois grupos estudados... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Antiretrovirals (ARV) interfere with viral enzymes resulting in the inhibition of HIV replication. The use of antiretroviral combinations has demonstrated highly effectiveness in controlling of the progression of HIV infection and increased of the patients' survival. However these benefits can be compromised by the development of drug resistance, as consequence of the mutations emergence in viral enzymes, representing a major obstacle to successful treatment of HIV-1 patients infected. Resistance tests, mainly HIV-1 genotyping, allow the orientation of new schemes, enabling the return of viral suppression. This study aimed to evaluate the profile of mutations and genotypic resistance to the Nucleoside Reverse Transcriptase Inhibitors (NRTI), Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI) and Protease Inhibitors (PI) in the patients in therapeutic failure submitted to the genotyping test, performed in Diagnostic Routine Laboratory in Molecular Biology at the Blood Center of FMB - UNESP, part of RENAGENO (National Network of HIV-1 Genotyping). HIV-1 pol region genomic sequences from all patients with genotype test performed during the years 2008 and 2009 were analyzed. The patients were separated in two distinct groups: "Adult group" (age ≥ 18 years), with 386 individuals, and "Pediatric group" (<18 years), with 45 patients, in a total of 431 patients. Genotyping was performed by Trugene HIV-1 Genotyping Kit (Siemens Healthcare Diagnostics). The sequences obtained were submitted to the Genotypic Resistance Interpretation Algorithm of Stanford University (HIVdb) and the subtyping was performed by REGA HIV-1 Subtyping Tool and by RIP 3.0 program. Subtype B was the most frequent in both groups followed by hybrid forms B and F (BF or FB) and subtype F1. Resistance mutations were found in 97.15% of patients in the adult group... (Complete abstract click electronic access below) / Orientador: Rejane Maria Tommasini Grotto / Coorientador: Maria Inês de Moura Campos Pardini / Banca: Dennis Armando Bertolini / Banca: Paulo Inácio da Costa / Mestre
|
16 |
In vitro transport abakaviru přes monovrstvu Caco-2 buněkꓼ interakce s etravirinem a rilpivirinem / In vitro transport of abacavir across the monolayer of Caco-2 cells; interaction with etravirine and rilpivirineMlčochová, Alice January 2018 (has links)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Alice Mlčochová Supervisor: PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: In vitro transport of abacavir across the monolayer of Caco-2 cells; interaction with etravirine and rilpivirine. Abacavir belongs among nucleoside reverse transciptase inhibitors (NRTIs) representing a basic component of combined antiretroviral therapy used in treatment of HIV-positive patients [1]. Etravirine and rilpivirine are newer non-nucleoside reverse transcriptase inhibitors (NNRTIs) combined in cART together with NRTI. ATP-dependent transporters, so called ABC transporters, are able to affect pharmacokinetic properties of drugs, thus they are important site of drug-drug interactions affecting absorption, distribution and excretion level. P-glycoprotein (Pgp, ABCB1) and BCRP (ABCG2) belong among the most clinically important ABC transporters able to cause drug-drug interactions. The aim of this thesis was to introduce and optimize the method for evaluation of drug absorption using monolayers of Caco-2human intestine cell lines, whose integrity was verified by evaluating TEER (transepithelial electrical resistance). This model was also used for abacavir transport studies. Significant...
|
17 |
Desenvolvimento e validação de metodologia por HPLC-PDA para monitoração terapêutica dos níveis plasmáticos de zidovudina e efavirenz / Development and validation of methodology for HPLC-PDA for therapeutic monitoring of plasma levels of zidovudine and efavirenzSOARES, Amanda Queiroz 01 October 2009 (has links)
Made available in DSpace on 2014-07-29T15:29:18Z (GMT). No. of bitstreams: 1
dissertacao amanda.pdf: 733204 bytes, checksum: a454e4fc6823529e279a29fcaea465c3 (MD5)
Previous issue date: 2009-10-01 / The therapeutic drug monitoring is an important tool to predict the
therapeutic efficacy and possible toxicity of antirretroviral agents used to treat
infection by human immunodeficiency virus (HIV). The goals of this study was to
develop and validate a method of analysis and extraction to quantify the
antirretrovirals efavirenz and zidovudine in human plasma, to know the clinical
profile and quantify the drugs efavirenz and zidovudine in plasma of volunteers
using treatment regimen efavirenz / lamivudine / zidovudine. Blood samples
were collected approximately 8 h after administration of AZT and 20 h of the
EFZ, were obtained from adult volunteers HIV positive in clinic monitoring at
Hospital das Clínicas, Universidade Federal de Goiás and therapeutic protocol
EFZ 600 mg once daily and lamivudine 150 mg + zidovudine 300 mg twice a
day. After solid phase extraction using cartridge Strata 18E C 500mg, 3 mL
capacity, the drugs and internal standard (5 - (4-methylphenyl)-5-fenilidantoína -
MPPH) were separated by reversed-phase column ACE 5 C18 100 x 4 6 mm.
The mobile phase consisted of acetonitrile and diethanolamine in water (pH 7.8),
flow rate 0.5 to 2.0 mL/min and detection at wavelength of 249 nm (EFZ), 267
nm (AZT) and 240 nm (MPPH). The method showed linearity at concentration
range of 50 to 5000 ng/mL for both drugs, with recovery of 84 and 92% for EFZ
and AZT, respectively. The limit of quantification (50 ng/mL), precision
(coefficient of variation <15%) and accuracy (relative errors <15%) are in
accordance with requirements of ANVISA. To evaluate the applicability of the
method, we analyzed plasma of volunteers (n = 12) with mean plasma
concentration of 1960 ± 766 ng/ mL to EFZ and 62.12 ± 16.21 ng/mL to AZT.
The method agree analytical parameters suitable for use in therapeutic
monitoring of patients using AZT and EFZ / A monitoração terapêutica de fármacos é uma importante ferramenta
para prever a eficácia terapêutica e a possível toxicidade dos agentes
antirretrovirais utilizados no tratamento da infecção pelo vírus da
imunodeficiência humana (HIV). Os objetivos deste estudo foram desenvolver e
validar uma técnica de análise e extração para quantificar os antirretrovirais
efavirenz e zidovudina no plasma humano, conhecer o perfil clínico e quantificar
os fármacos efavirenz e zidovudina no plasma dos sujeitos da pesquisa em uso
do esquema terapêutico efavirenz/lamivudina/zidovudina. Amostras de sangue,
coletadas aproximadamente 8 h após administração do AZT e 20 h do EFZ,
foram obtidas de sujeitos adultos com diagnóstico HIV positivo em
acompanhamento no Hospital das Clínicas da Universidade Federal de Goiás
com protocolo terapêutico EFZ 600 mg uma vez ao dia e lamivudina 150 mg +
zidovudina 300 mg duas vezes ao dia. Após extração em fase sólida utilizando
cartucho Strata C 18E 500mg, 3mL de capacidade, os fármacos e padrão
interno (5-(4-metilfenil)-5-fenilidantoína MPPH) foram separados em coluna
fase reversa ACE 5, C18 100 x 4,6 mm. A fase móvel utilizada foi composta por
acetonitrila e dietanolamina em água (pH 7,8), vazão de 0,5 a 2,0 mL/min e
detecção no comprimento de onda 249 nm (EFZ), 267 nm (AZT) e 240 nm
(MPPH). A técnica apresentou linearidade no intervalo de 50 a 5000 ng/mL para
ambos os compostos, com recuperação média de 84 e 92% para a AZT e EFZ,
respectivamente. O limite de quantificação (50 ng/mL), precisão (coeficiente de
variação < 15%) e exatidão (erros relativos < 15%) estão de acordo com
exigências da ANVISA. Para avaliar a aplicabilidade da técnica, analisou-se
amostras de plasma de sujeitos (n = 12), obtendo uma concentração plasmática
média de 1960 ± 766 ng/mL para EFZ e 62,12 ± 16,21 ng/mL para o AZT. A
técnica apresentou parâmetros analíticos adequados à sua utilização em
monitoração terapêutica de pacientes em uso de AZT e EFZ
|
18 |
Avaliação in vitro da solubilidade e da permeabilidade da lamivudina e da zidovudina. Aplicações na classificação biofarmacêutica / Solubility and permeability evaluation of lamivudine and zidovudine. Biopharmaceutical classification.Andre Bersani Dezani 21 October 2010 (has links)
A biodisponibilidade é o fator determinante da eficácia clínica de um fármaco e depende diretamente das propriedades de solubilidade e permeabilidade da substância ativa. O Sistema de Classificação Biofarmacêutica (SCB), baseado nestas características, consolidou-se nos últimos anos como ferramenta de auxílio na predição da biodisponibilidade de fármacos. O SCB tem sido empregado no desenvolvimento de formas farmacêuticas, contendo novos fármacos ou não, e no registro de medicamentos genéricos, por conta das limitações técnicas, econômicas e éticas para a realização dos ensaios diretos de biodisponibilidade. Assim, a avaliação das propriedades de solubilidade e permeabilidade dos fármacos, embora indiretamente, oferece objetivas indicações sobre a eficácia dos medicamentos, com vantagem de consolidar modelos in vitro, mais facilmente reprodutíveis, sem trazer riscos a voluntários sadios. Dentre os estudos de solubilidade destaca-se o método do equilíbrio que emprega a técnica de shake-flask. Para a determinação da permeabilidade in vitro, diferentes técnicas têm sido empregadas, dentre as quais destacam-se modelos que empregam tecido intestinal de animais. O presente trabalho teve como objetivos a avaliação da solubilidade e da permeabilidade de fármacos antirretrovirais (lamivudina e zidovudina) e o desenvolvimento de protocolo para determinação da permeabilidade em segmentos de intestino de ratos, por meio de modelo in vitro em ensaios com células de Franz. A solubilidade dos fármacos propostos foi caracterizada pela técnica shake-flask e por meio da dissolução intrínseca, sendo que os resultados permitiram concluir que, segundo o SCB, os fármacos zidovudina e lamivudina apresentam alta solubilidade. Os ensaios de permeabilidade demonstram que o método proposto é viável e os valores de permeabilidade da lamivudina e da zidovudina sugerem que ambos os fármacos podem ser classificados como de alta permeabilidade. / Bioavailability is the determinant of the clinical efficacy of a drug and is directly dependent on the properties of solubility and permeability of the active substance. The Biopharmaceutical Classification System (BCS), based on these characteristics, has become in recent years as a tool to aid in predicting the bioavailability of drugs. The BCS has been used in the development of dosage forms, containing new drugs or not, and the registration of generic drugs, since there are technical limitations, economic and ethical guidelines for the testing of direct bioavailability. Thus, the evaluation of the solubility and permeability of the drugs, although indirectly, provides objective indications on the effectiveness of medicines, with the advantages of consolidating in vitro models more easily reproducible without bringing risk to healthy volunteers. Among the solubility studies highlight the shake-flask method, recommended by regulatory agencies. To determine the in vitro permeability, different techniques have been employed, among which stand out models based on intestinal tissue obtained from different animals. This study aims to evaluate the solubility and permeability of antiretroviral drugs (lamivudine and zidovudine), and the development of protocol for the determination of permeability in intestine segments of rats using in vitro model in experimental Franz cells. So far, the solubility of proposed drugs was characterized by shake-flask method and through the intrinsic dissolution. About the solubility, results showed that, according to BCS, the drugs zidovudine and lamivudine has high solubility. About the intrinsic dissolution, results showed agreement with the results of the solubility. Permeability tests showed that the proposed method is feasible and the permeability values of lamivudine and zidovudine suggest that both drugs can be classified as high permeability.
|
19 |
A IMPORTÂNCIA DA ATENÇÃO FARMACÊUTICA NA ADESÃO A TERAPIA ANTIRRETROVIRAL NO HIV/AIDS / THE IMPORTANCE OF PHARMACEUTICAL CARE IN ADHERENCE TO ANTIRETROVIRAL THERAPY ON HIV / AIDSVielmo, Laura 23 July 2013 (has links)
With chronicity of AIDS and the increasing number of patients on Antiretroviral
Therapy (ART) monitoring of adherence to treatment has become a priority in public health,
for maintenance of high rates of adherence depends on the success of treatment.
In front of a situation of chronic disease, challenges arise, determining the need for
new practices related to adherence monitoring of People Living with HIV/AIDS (PLWHA)
and before this context, the Pharmaceutical Care presents itself as an instrument to improve
adherence to TARV, since studies show that the Pharmaceutical Care is able to improve
adherence.
So, the objective was to evaluate the influence of Pharmaceutical Care on adherence to
antiretrovirals in PVHA starting treatment in a Dispenser Unit Antiretroviral Drugs (UDM).
The longitudinal study has been realized with convenience sampling where included
patients starting TARV in naïve patients, were divided into two study groups. The
intervention group received Pharmaceutical care and monitoring, while the control group
followed the routine care of the service. Adherence to treatment was confirmed by self-report,
regular withdrawals of ARV and evolution of viral load.
The profile of PLHA included in this study presented social demographic
characteristics that follow the national epidemiological trends. Adherence to antiretroviral
therapy showed better results in the intervention group. It was found that the highest number
of dropouts in the control group occurred when patients given medical follow-up in public
health services compared with individuals.
The results of the study allowed the development of a protocol for application in
Pharmaceutical care routine UDM. / Com a cronicidade da AIDS e o crescente número de pacientes em uso de Terapia
Antirretroviral (TARV) a monitorização da adesão ao tratamento se tornou uma das
prioridades em saúde pública, pois da manutenção de altas taxas de adesão depende o sucesso
do tratamento. Diante do quadro de cronicidade da doença, surgem desafios, determinando a
necessidade de novas práticas relacionadas ao monitoramento da adesão das Pessoas Vivendo
com HIV/AIDS (PVHA) e diante desse contexto, a Atenção Farmacêutica apresenta-se como
um dos instrumentos para melhorar a adesão a TARV, uma vez que estudos mostram que a
Atenção Farmacêutica é capaz de melhorar a adesão. Assim, objetivou-se avaliar a influência
da Atenção Farmacêutica na adesão aos antirretrovirais em PVHA em início de tratamento em
uma Unidade Dispensadora de Medicamentos Antirretrovirais (UDM). Para tal, foi realizado
um estudo longitudinal com amostragem por conveniência onde se incluiu pacientes em início
de TARV virgens de tratamento, alocados em dois grupos de estudo. O grupo intervenção
recebeu Atenção Farmacêutica e acompanhamento, enquanto que, o grupo controle seguiu a
rotina de atendimento do serviço. A adesão ao tratamento foi comprovada através de
autorrelato, regularidade nas retiradas de ARV e evolução da carga viral. O perfil das PVHA
incluídas neste estudo apresentou características sócias demográficas que seguem as
tendências epidemiológicas nacionais. A adesão a TARV apresentou melhores resultados no
grupo de intervenção. Verificou-se que, o maior número de abandonos no grupo controle
ocorreu quando os pacientes recebiam acompanhamento médico nos serviços de saúde
público em comparação com os particulares. Os resultados do estudo permitiram o
desenvolvimento de um Protocolo de Atenção Farmacêutica para aplicação na rotina da
UDM.
|
20 |
Au-delà du traitement du sida : une anthropologie de l’échec thérapeutique au Cameroun / Beyond AIDS treatment : an anthropology of treatment failure in CameroonLaborde-Balen, Gabrièle 19 December 2016 (has links)
Alors que l’accès aux traitements antirétroviraux se généralise dans les pays en développement, l’émergence de résistances virales, liées aux échecs thérapeutiques, constitue une menace sur un plan individuel et collectif. Au Cameroun, la prévention, la détection et la prise en charge des échecs thérapeutiques se heurtent à différentes contraintes. A travers une approche anthropologique, cette thèse explore le contexte et les déterminants des échecs thérapeutiques. Le défaut d’observance est la principale cause de leur survenue. Les équipes médicales et psychosociales font face à l’absence de guides et de procédures adaptées. Aussi l’annonce de l’échec est-elle souvent associée à une culpabilisation des patients, auxquels les soignants attribuent la seule responsabilité de l’échec. L’adaptation des structures est limitée. La prise en charge médicale et psychosociale est focalisée sur le démarrage du traitement et le changement de traitement, mais le suivi à long terme est inexistant. La perception, par les patients, des médicaments antirétroviraux, est perturbée par la survenue de l’échec. L’échec redéfinit les relations de pouvoir et de confiance entre les soignants et les patients. L’attitude des soignants oscille entre compassion et réprobation, alors que l’échec renforce la dépendance des patients. Cette thèse vise à contribuer aux réflexions anthropologiques sur les médicaments, le système de santé et les relations soignants-soignés mais aussi à contribuer à l’amélioration de la prise en charge des patients en échec, pour préserver l’efficacité des thérapies antirétrovirales, sur laquelle repose l’espoir, d’éradiquer un jour l’épidémie. / When antiretroviral treatment becomes widespread in countries in the Global South, the emergence of viral resistance related to treatment failures is a threat for individuals and the general public. In Cameroon, various constraints hinder the prevention, detection and case management of treatment failures. Through an anthropological approach, this dissertation explores the context and determinants of treatment failures. Nonadherence is the main cause of their onset. Medical and psychosocial teams must face a lack of suitable guidelines and procedures. Also, notification of the failure is often associated with placing blame on patients, on whom caregivers assign sole responsibility for the failure. Adaptation in facilities is limited. Medical and psychosocial care is focused on starting treatment and making changes in treatment, but long-term follow-up does not exist. Patients’ perceptions of antiretrovirals are hampered by failures. The failure redefines power relationships and trust between caregivers and patients. Caregivers’ attitudes vacillate between compassion and condemnation, while the failure reinforces the patients’ dependence. This dissertation aims to contribute to the anthropological discussion on medicines, the health system and the caregiver-patient relationship as well as to improve care for patients with treatment failure to ensure the continued effectiveness of antiretroviral therapies that underlie any hopes of one day eradicating the epidemic.
|
Page generated in 0.0627 seconds