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101. Impact of antiretroviral resistance and virological failure on HIV-1 informational entropy.

Author

Lima, Elidamar Nunes de Carvalho, Piqueira, José Roberto Castilho, Camargo, Michelle, Galinskas, Juliana, Sucupira, Maria Cecilia, and Diaz, Ricardo Sobhie

Subjects
HIV infection genetics, ANTIRETROVIRAL agents, DNA polymerases, DRUG resistance in microorganisms, HIV, HIV infections, GENETIC mutation, PROTEOLYTIC enzymes, T cells, VIRAL load, TREATMENT effectiveness, CD4 lymphocyte count, SEQUENCE analysis
Abstract

Objectives: The present study investigated the relationship between genomic variability and resistance of HIV-1 sequences in protease (PR) and reverse transcriptase (RT) regions of the pol gene. In addition, we analysed the resistance among 651 individuals presenting antiretroviral virological failure, from 2009 to 2011, in the state of São Paulo, Brazil.Methods: The genomic variability was quantified by using informational entropy methods and the relationship between resistance and replicative fitness, as inferred by the residual viral load and CD4+ T cell count.Results: The number of antiretroviral schemes is related to the number of resistance mutations in the HIV-1 PR (α = 0.2511, P = 0.0003, R2 = 0.8672) and the RT (α = 0.7892, P = 0.0001, R2 = 0.9141). Increased informational entropy rate is related to lower levels of HIV-1 viral loads (α = -0.0121, P = 0.0471, R2 = 0.7923), lower levels of CD4+ T cell counts (α = -0.0120, P = 0.0335, R2 = 0.8221) and a higher number of antiretroviral resistance-related mutations.Conclusions: Less organized HIV genomes as inferred by higher levels of informational entropy relate to less competent host immune systems, lower levels of HIV replication and HIV genetic evolution as a consequence of antiretroviral resistance. [ABSTRACT FROM AUTHOR]

Published
2018
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102. The Virological and Immunological Characteristics of the HIV-1-Infected Population in Brazil: From Initial Diagnosis to Impact of Antiretroviral Use

Author

Diaz, Ricardo Sobhie, primary, Inocêncio, Lilian A., additional, Sucupira, Maria Cecilia Araripe, additional, Pereira, Anderson Alvarenga, additional, Hunter, James, additional, Ferreira, João Eduardo, additional, Araújo, Luciano V., additional, Souza, Denise F. C., additional, and Sabino, Ester Cerdeira, additional

Published
2015
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103. Epigenetic Modulations in Activated Cells Early after HIV-1 Infection and Their Possible Functional Consequences

Author

Maricato, Juliana T., primary, Furtado, Maria N., additional, Takenaka, Maisa C., additional, Nunes, Edsel R. M., additional, Fincatti, Patricia, additional, Meliso, Fabiana M., additional, da Silva, Ismael D. C. G., additional, Jasiulionis, Miriam G., additional, Cecília de Araripe Sucupira, Maria, additional, Diaz, Ricardo Sobhie, additional, and Janini, Luiz M. R., additional

Published
2015
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105. Brazilian Journal of Infectious Diseases

Author

Diaz, Ricardo Sobhie, Sucupira, Maria Cecilia A, Vergara, Tania RC, Brites, Carlos, Bianco, Rosana Del, Bonasser Filho, Francisco, and Colares, Geova Keny B

Subjects
Virtual phenotype, Antiretroviral resistance, Genotype, Brazil
Abstract

Acesso restrito: Texto completo. p. 489-494. Submitted by JURANDI DE SOUZA SILVA (jssufba@hotmail.com) on 2012-04-19T12:33:56Z No. of bitstreams: 1 __www.scielo.br_pdf_bjid_v14n5_v14n5a11.pdf: 250392 bytes, checksum: 87c0cb8c22fe470219a8e1d807a327b6 (MD5) Made available in DSpace on 2012-04-19T12:33:56Z (GMT). No. of bitstreams: 1 __www.scielo.br_pdf_bjid_v14n5_v14n5a11.pdf: 250392 bytes, checksum: 87c0cb8c22fe470219a8e1d807a327b6 (MD5) Previous issue date: 2010 Objective: To investigates how the use of HIV-1 resistance tests infl uences physician decision-making. Methods: Ten experienced reference physicians from the Brazilian Network for Drug Resistance each received ten patients’ case histories. The selected patients had experienced at least two virological failures. First, reference physicians were asked to empirically select a new regimen for each patient. Second, after genotype report (ViroSeq 2.6) was provided, and physicians were again asked to select a new regimen considering this additional information. Finally, they were asked to select a regimen after receiving a virtual phenotype result (vircoTYPE 3.9.00). Results: In 79% of the cases, physicians changed their empirical choice of regimen after receiving the genotype report, resulting in an increase in the mean number of active drugs from 1.8 to 2.2 (p = 0.0003), while the average number of drugs/regimen remained at 4.0. After receipt of the virtual phenotype report, additional changes were made in 75% of the patient cases, resulting in an increase in the number of active drugs to 2.8 (p < 0.0001), while the average number of drugs/ regimen remained at 4.0. After receipt of the genotype report, 48% of the changes were in NRTIs, 29% were in NNRTIs and 60% were in PIs; after consideration of the virtual phenotype, 61%, 10% and 49% of the changes, respectively, were in these categories of drugs. Fourteen percent of the physicians rated the genotype report as “extremely useful”, whereas 34% rated the subsequent virtual phenotype report as “extremely useful” (p = 0.0003). Conclusions: Resistance testing has a signifi cant impact on physicians’ choices of antiretroviral salvage therapies, and it promotes the selection of more active drugs. Salvador

Published
2010
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107. Genetic Diversity of HIV-1 Gene vif Among Treatment-Naive Brazilians.

Author

Villanova, Fabiola, Barreiros, Marta, Janini, Luiz Mário, Diaz, Ricardo Sobhie, and Leal, Élcio

Abstract

HIV-1 has the Vif protein, which binds to human antiviral proteins APOBEC3 to form complexes to be degraded by cellular proteolysis. To further explore HIV-1 diversity at the population level, we analyzed blood samples from 317 treatment-naive patients in Brazil. In this study, we explored the correlations of Vif polymorphisms with clinical parameters of the patients and found that mutation K22H is associated with low CD4+ cell counts and higher viral loads. Phylogenetic analysis of the vif gene indicated that subtype B was predominant in ∼77% (243/317) of the patients, followed by HIV-1 F ∼18% (56/317), and subtype C ∼4% (12/317); five samples were BF recombinants (∼1% of patients), and one was an AG recombinant. On the basis of the vif gene, we detected the presence of one AG and several previously unknown BF intersubtypes in this population. The global mean diversity, measured by pairwise distances, was 0.0931 ± 0.0006 among sequences of subtype B ( n = 243), whereas the mean diversity of subtype C sequences ( n = 12) was 0.0493 ± 0.001 and that of subtype F ( n = 56) was 0.050 ± 0.001. [ABSTRACT FROM AUTHOR]

Published
2017
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108. In VivoHIV-1 Hypermutation and Viral Loads Among Antiretroviral-Naive Brazilian Patients

Author

de Lima-Stein, Mariana Leão, primary, Alkmim, Wagner Tadeu, additional, Bizinoto, Maria Clara de Souza, additional, Lopez, Luis Fernandez, additional, Burattini, Marcelo Nascimento, additional, Maricato, Juliana Terzi, additional, Giron, Leila, additional, Sucupira, Maria Cecília Araripe, additional, Diaz, Ricardo Sobhie, additional, and Janini, Luiz Mario, additional

Published
2014
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112. Prevalence of Human Leukocyte Antigen HLA-B*5701 in HIV-1 Infected Individuals in Brazil

Author

Araújo, Claudinéia de, primary, Carvalho, Cristina Valetta de, additional, Souza Freire, Miriam Estela de, additional, Yamaguti, Amanda, additional, Scaff, Ivens Cuiabano, additional, Souza, Fernando José de, additional, Silvestre Silva, Flávia Galindo, additional, Diaz, Ricardo Sobhie, additional, and Guerreiro da Silva, Ismael Dale Cotrim, additional

Published
2014
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113. A specific subtype C of human immunodeficiency virus type 1 circulates in Brazil

Author

Soares, M. A., Oliveira, T. de, Brindeiro, R. M., Diaz, Ricardo Sobhie [UNIFESP], Sabino, E. C., Brigido, L., Pires, I. L., Morgado, M. G., Dantas, M. C., Barreira, D., Teixeira, P. R., Cassol, S., Tanuri, A., Brazilian Network Drug Reistance S, Universidade Federal do Rio de Janeiro (UFRJ), Univ Natal, Universidade Federal de São Paulo (UNIFESP), Universidade de São Paulo (USP), Inst Adolfo Lutz Registro, Inst Biol Exercito, Fdn Inst Oswaldo Cruz, and Minist Saude

Subjects
subtype polymorphism, subtype C, HIV in primary infection, drug resistance mutations, signature sequence
Abstract

Objective: To characterize the subtype C strains of HIV type I that circulate in Brazil, especially those originated from the southern part of the country.Design and methods: One hundred and twelve HIV-1-positive subjects had their plasma viral RNA extracted. Protease (PR) and reverse transcriptase (RT) genomic regions were polymerase chain reaction-amplified and sequenced for subtype determination. Subtype C strains were selected and compared to other strains of this subtype from the database, and specific amino acid signature patterns were searched.Results: Brazilian subtype C viruses form a very strong monophyletic group when compared to subtype C viruses from other countries and presented specific signature amino acids. Recombinants between subtype C and B viruses have been documented in areas of co-circulation. the incidence of primary PR and RT inhibitor resistance mutations in drug-naive subjects was observed. An increasing number of secondary resistance mutations was also seen, some of which are characteristic of subtype C-related sequences.Conclusions: Introduction of subtype C of HIV-1 in Brazil was likely a single event of one or a mixture of similarly related strains. Recombination between subtype C and B viruses is an ongoing process in the country. Primary and secondary drug resistance mutations were observed, although some of the secondary mutations could be associated with subtype C molecular signatures. Subtype-specific polymorphisms of PR and RT sequences found in this subtype C Brazilian variant might influence this emergence and have an impact on HIV treatment and on vaccine development in the country. (C) 2003 Lippincott Williams Wilkins. Univ Fed Rio de Janeiro, Dept Genet, Mol Virol Lab, Ilha Fdn, BR-21944970 Rio de Janeiro, Brazil Univ Natal, Nelson Mandela Sch Med, Africa Ctr, HIV Mol Virol & Bioinformat Unit 1, ZA-4001 Durban, South Africa UNIFESP, Escola Paulista Med, Lab Retrovirol, São Paulo, Brazil Univ São Paulo, Hemoctr São Paulo, Fdn Prosangue, São Paulo, Brazil Inst Adolfo Lutz Registro, Lab Retrovirol, São Paulo, Brazil Inst Biol Exercito, Virol Lab, Rio de Janeiro, Brazil Fdn Inst Oswaldo Cruz, Dept Imunol, BR-20001 Rio de Janeiro, Brazil Minist Saude, CN DST AIDS, Brasilia, DF, Brazil UNIFESP, Escola Paulista Med, Lab Retrovirol, São Paulo, Brazil Web of Science

Published
2003

114. Detection of lamivudine-resistant variants and mutations related to reduced antigenicity of HBsAg in individuals from the cities of Santos and São Paulo, Brazil

Author

Mantovani, Nathalia, primary, Cicero, Maira, additional, Santana, Luiz Claudio, additional, Silveira, Carla, additional, do Carmo, Eliane Pereira, additional, Abrão, Paulo Roberto Ferreira, additional, Diaz, Ricardo Sobhie, additional, Caseiro, Marcos Montani, additional, and Komninakis, Shirley Vasconcelos, additional

Published
2013
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116. Codon pairs of the HIV-1 vif gene correlate with CD4+ T cell count

Author

Bizinoto, Maria Clara, primary, Yabe, Shiori, additional, Leal, Élcio, additional, Kishino, Hirohisa, additional, de Oliveira Martins, Leonardo, additional, de Lima, Mariana Leão, additional, Morais, Edsel Renata, additional, Diaz, Ricardo Sobhie, additional, and Janini, Luiz Mário, additional

Published
2013
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120. Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco

Author

Cavalcanti, Ana Maria Salustiano, primary, Brito, Ana Maria de, additional, Salustiano, Daniela Medeiros, additional, Lima, Kledoaldo Oliveira de, additional, Silva, Sirleide Pereira da, additional, Diaz, Ricardo Sobhie, additional, and Lacerda, Heloisa Ramos, additional

Published
2012
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121. Faster HIV-1 Disease Progression among Brazilian Individuals Recently Infected with CXCR4-Utilizing Strains

Author

Sucupira, Maria Cecilia Araripe, primary, Sanabani, Sabri, additional, Cortes, Rodrigo M., additional, Giret, Maria Teresa M., additional, Tomiyama, Helena, additional, Sauer, Mariana M., additional, Sabino, Ester Cerdeira, additional, Janini, Luiz Mario, additional, Kallas, Esper Georges, additional, and Diaz, Ricardo Sobhie, additional

Published
2012
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138. Characterization of the Full-Length Human Immunodeficiency Virus-1 Genome from Recently Infected Subjects in Brazil

Author

Sa-Filho, Dercy, primary, Kallas, Esper G., additional, Sanabani, Sabri, additional, Sabino, Ester, additional, Sucupira, Maria Cecilia, additional, Sanchez-Rosa, Ana Carolina, additional, Tescarollo, Graziela, additional, Tomiyama, Helena, additional, Bassichetto, Katia, additional, Janini, Luis Mario, additional, and Diaz, Ricardo Sobhie, additional

Published
2007
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147. In Vivo HIV-1 Hypermutation and Viral Loads Among Antiretroviral-Naive Brazilian Patients.

Author

de Lima-Stein, Mariana Leão, Alkmim, Wagner Tadeu, Bizinoto, Maria Clara de Souza, Lopez, Luis Fernandez, Burattini, Marcelo Nascimento, Maricato, Juliana Terzi, Giron, Leila, Sucupira, Maria Cecília Araripe, Diaz, Ricardo Sobhie, and Janini, Luiz Mario

Abstract

Hypermutation alludes to an excessive number of specific guanine-to-adenine (G- >A) substitutions in proviral DNA and this phenomenon is attributed to the catalytic activity of cellular APOBECs. Population studies relating hypermutation and the progression of infection by human immunodeficiency virus type 1 (HIV-1) have been performed to elucidate the effect of hypermutation on the natural course of HIV-1 infection. However, the many different approaches employed to assess hypermutation in nucleotide sequences render the comparison of results difficult. This study selected 157 treatment-naive patients and sought to correlate the hypermutation level of the proviral sequences in clinical samples with demographic variables, HIV-1 RNA viral load, and the level of CD4+ T cells. Nested touchdown polymerase chain reaction (PCR) was performed with specific primers to detect hypermutation in the region of HIV-1 integrase, and the amplified sequences were run in agarose gels with HA-Yellow. The analysis of gel migration patterns using the k-means clustering method was validated by its agreement with the results obtained with the software Hypermut. Hypermutation was found in 31.2% of the investigated samples, and a correlation was observed between higher hypermutation levels and higher viral load levels. These findings suggest a high frequency of hypermutation detection in a Brazilian cohort, which can reflect a particular characteristic of this population, but also can result from the method approach by aiming at hypermutation-sensitive sites. Furthermore, we found that hypermutation events are pervasive during HIV-1 infection as a consequence of high viral replication, reflecting its role during disease progression. [ABSTRACT FROM AUTHOR]

Published
2014
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148. A Phase III, randomized study to evaluate the immunogenicity and safety of an MF59®-adjuvanted A/H1N1 pandemic influenza vaccine in HIV-positive adults.

Author

Diaz, Ricardo Sobhie, Tenore, Simone Barros, da Silva, Mônica M. Gomes, and da Cunha, Clovis Arns

Abstract

Background and aims Antibody responses to vaccines are suboptimal in immunosuppressed HIV-positive individuals. This study aimed to evaluate the potential benefits of MF59® adjuvant or a second A/H1N1 influenza vaccine dose in HIV-positive adults. Method HIV-positive adults ( n = 61) and HIV-negative controls ( n = 93) aged 18–60 years received two doses of A/H1N1, either as MF59-adjuvanted A/H1N1 pandemic vaccine, or as part of a unadjuvanted seasonal influenza vaccine containing the pandemic strain. Immunogenicity was assessed against the vaccine strain, A/California/7/2009, by haemagglutination inhibition (HI) assay three weeks after the administration of each vaccine dose. Local and systemic reactions were recorded for three days after each vaccination. Unsolicited adverse events were recorded throughout the six-week study period. Results Both adjuvanted and unadjuvanted vaccines met the European licensure criteria in HIV-positive and HIV-negative study groups after a single dose. Lower antibody titres were observed with both adjuvanted and unadjuvanted vaccine in HIV-positive compared to HIV-negative subjects. A second dose of either vaccine did not compensate for the lower response of HIV-infected subjects. In HIV-positive subjects, CD4 + T cell counts and levels of CD38 expression on CD8 + T cells remained stable throughout the study period. Both vaccine formulations were generally well tolerated, with no increased reactogenicity observed in response to the adjuvanted vaccine. Conclusion Antibody responses in HIV-positive subjects were acceptable but lower than those in healthy control subjects, whether subjects were immunized with one or two doses of adjuvanted or unadjuvanted vaccine. Vaccination did not affect rates of HIV replication, CD4 + T cells counts, or levels of CD38 expression among patients under successful antiretroviral treatment. [ABSTRACT FROM AUTHOR]

Published
2014
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150. Effects of Carbon Nanomaterials and Aloe vera on Melanomas—Where Are We? Recent Updates.

Author

de Carvalho Lima, Elidamar Nunes, Barros Martins, Guilherme Leão, Diaz, Ricardo Sobhie, Schechter, Mauro, Piqueira, José Roberto Castilho, and Justo, João Francisco

Subjects
*ALOE, *NANOSTRUCTURED materials, *ALOE vera, *MELANOMA, *SKIN cancer, *DEATH rate, *CARBON
Abstract

Melanoma is an aggressive skin cancer that affects approximately 140,000 people worldwide each year, with a high fatality rate. Available treatment modalities show limited efficacy in more severe cases. Hence, the search for new treatment modalities, including immunotherapies, for curing, mitigating, and/or preventing cancer is important and urgently needed. Carbon nanoparticles associated with some plant materials, such as Aloe vera, have shown appealing antineoplastic activity, derived mainly from the compounds aloin, aloe-emodin, barbaloin acemannan, and octapeptide, thus representing new possibilities as antitumor agents. This systematic review aims to arouse interest and present the possibilities of using Aloe vera combined with carbon-based nanomaterials as an antineoplastic agent in the treatment and prevention of melanoma. Limitations and advances in melanoma treatment using functionalized carbon nanomaterials are discussed here. Moreover, this review provides the basis for further studies designed to fully explore the potential of carbon nanomaterials associated with Aloe vera in the treatment of various cancers, with a focus on melanoma. [ABSTRACT FROM AUTHOR]

Published
2022
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