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Evolução das mutações de resistência aos inibidores de protease em pacientes infectados pelo HIV-1 subtipo F; Evolution of protease inhibitor resistance mutations in HIV-1 subtype F infected patients

Oliveros, Marcia Perez Resende
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 24/09/2009 PT
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A elevada variabilidade genética do HIV tipo 1 e a seleção de mutações de resistência às drogas antirretrovirais tem representado um enorme desafio para o sucesso dos esquemas terapêuticos. Muitos estudos têm demonstrado que há padrões específicos de mutações para cada um dos subtipos de HIV-1. Os padrões do subtipo B são os mais bem definidos em função de sua presença majoritária nas epidemias da Europa e Estados Unidos. Contudo, a prevalência dos subtipos não-B, assim como a das formas recombinantes, tem aumentado significativamente em várias regiões. No Brasil, onde os subtipos B e F, e em alguns estados, também o C, coexistem, a presença de recombinantes BF vem ganhando destaque. Os objetivos deste trabalho foram comparar a região da protease do recombinante BF e do subtipo F puro quanto à possível presença de substituições diferentes, analisar o perfil mutacional e a covariação de mutações associadas ao tratamento e ao uso de inibidores específicos na protease do HIV-1 subtipo F e avaliar a reversão de mutações que já haviam sido selecionadas e a seleção de novas mutações após a troca do esquema terapêutico; The high genetic variability of HIV type 1 and the selection of antiretroviral resistance mutations have represented an enormous challenge to therapeutic schema success. Many studies have demonstrated that there are specific mutations patterns for each of the HIV-1 subtypes. Subtype B mutation profiles are the best studied due to its high presence in Europe and USA epidemics. However...

Resolução estrutural cristalográfica de proteases de HIV-1 de subtipos brasileiros e estudos estruturais da l-asparginase de Escherichia coli; Crystallographic structure solution of Brazilian subtypes of HIV-1 proteases and structural studies of E. coli L-asparaginase

Matilde Junior, Mario Sanches
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 17/12/2004 PT
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Um dos maiores problemas encontrados em terapias anti-retrovirais contra AIDS é a emergência de variantes virais que exibem resistência aos fármacos disponíveis e subtiposvirais naturalmente mais suscetíveis ao desenvolvimento de falha terapêutica. Neste trabalho nós resolvemos as estruturas cristalográficas de quatro proteases de HIV-1 complexadas com o inibidor universal C2 simétrico TL-3. As proteases utilizadas foram extraídas de pacientes com AIDS, uma do subtipo B selvagem (Bwt), uma do subtipo F selvagem (Fwt), e um mutante de cada um dos subtipos (Bmut e Fmut), esses dois últimos de pacientes apresentando falha terapêutica. As proteínas foram produzidas por expressão heteróloga em bactérias Escherichia coli, purificadas à partir das proteínas dos corpos de inclusão, e reenoveladas. Os dados coletados foram processados à uma resolução de 2.1 A para o complexo Bwt:TL-3, 1.75 A para Bmut:TL-3, 2.1 A para Fwt:TL-3 e 2.8 A para Fmut:TL-3. Esses dados foram inicialmente processados em P6122 e, posteriormente, reprocessados em P6i. As estruturas foram resolvidas por substituição molecular utilizando a estrutura de uma protease de HIV-1 publicada como modelo. A análise dessas quatro estruturas mostrou que o inibidor TL-3 liga-se de maneira muito próxima em todas elas. Nas proteases Bmut e Fmut a mutação V82A causa um reempacotamento do bolsão SI'...

Molecular epidemiology of HIV-1 in Venezuela: high prevalence of HIV-1 subtype B and identification of a B/F recombinant infection

Castro, Erika; Echeverr??a, Gloria; Deibis, Leopoldo; Gonz??lez de Salmen, Beatr??z; Moreira, Aline Dos Santos; Guimar??es, Monick Lindenmeyer; Bastos, Francisco In??cio Pinkusfeld Monteiro; Morgado, Mariza Gon??alves
Fonte: Lippincott Williams & Wilkins, Inc., Philadelphia Publicador: Lippincott Williams & Wilkins, Inc., Philadelphia
Tipo: Artigo de Revista Científica
EN
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1Erika Castro, 2Gloria Echeverr??a, 2Leopoldo Deibis, 3Beatr??z Gonz??lez de Salmen, 1Aline Dos Santos Moreira, 1Monick L. Guimar??es, 4Francisco I. Bastos, and 1Mariza G. Morgado 1Department of Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil; 2Non Governmental Organization, CRIATEII, Porlamar, Margarita Island, Venezuela; 3Immunology Institute, Central University of Venezuela, Caracas, Venezuela; STDs and AIDS Program, State Hospital ???Luis Ortega,??? Porlamar, Margarita Island, Venezuela; and 4Department of Health Information, CICT, FIOCRUZ, Rio de Janeiro, Brazil; Summary: The authors assessed HIV-1 variability in two distinct areas of Venezuela (the capital Caracas and Margarita Island) through the analysis of blood specimens and clinical and epidemiologic data of 72 persons. Proviral DNA was evaluated through heteroduplex mobility assay (HMA) based on the envelope region. Additionally, FOK I restriction enzyme digestion assay was performed in all subtype B ED31/33 amplified products to check the presence of the typical Brazilian subtype B GWGR variant. Sequencing and phylogenetic analysis for C2-V3 region of gp120 was performed in selected cases. The vast majority of samples were found to belong to subtype B...

Retrovirus infections in a sample of injecting drug users in Rio de Janeiro City, Brazil: prevalence of HIV-1 subtypes, and co-infection with HTLV-I/II

Guimar??es, Monick Lindenmeyer; Bastos, Francisco In??cio Pinkusfeld Monteiro; Dias, Paulo Roberto Telles Pires; Castro Filho, Bernardo Galv??o ; Diaz, Ricardo S.; Bongertz, Vera; Morgado, Mariza Gon??alves
Fonte: Elsevier Science B.V. Publicador: Elsevier Science B.V.
Tipo: Artigo de Revista Científica
EN
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Background :Retrovirus infections among injecting drug users (IDUs), a core at-risk population for both HIV-1 and HTLV-I/II infections in Brazil, were assessed within an ongoing cooperative research. Objecti e : The study assessed the seroprevalences of HIV-1 and HTLV-I/II infections, as well as the prevalence of HIV-1 subtypes in a sample of IDUs from Rio de Janeiro, Brazil. An attempt to evaluate HIV incidence was carried out using a dual ???sensitive/less sensitive??? testing strategy. Study design : Cross-sectional evaluation of 175 IDUs. Serostatus for HIV-1 and HTLV-I/II were established by enzyme-linked immunosorbent assays, and confirmed by western blot. The dual testing strategy aimed to estimate HIV-1 incidence rates. Differentiation between HTLV-I and -II was performed by western blot. DNA samples were polymerase chain reaction amplified by a nested protocol, and HIV-1 subtyping was determined by heteroduplex mobility assay. Results : Forty-six and 29 samples were found to be, respectively, positive for HIV-1 and HTLV-I/II, 15 of them co-infected by both viruses. Among HTLV-I/II-infected patients, 75.9% were infected by HTLV-I. Thirty-one HIV samples were identified as B subtype, with seven of them showing the typical ???Brazilian B??? pattern in the gp120 V3 loop...

High prevalence and association of HIV-1 non-B subtype with specific sexual transmission risk among antiretroviral naïve patients in Porto Alegre, RS, Brazil

Dias,Cláudia Fontoura; Nunes,Cynara Carvalho; Freitas,Isabela Osório; Lamego,Isabel Saraiva; Oliveira,Ilda Maria Rodrigues de; Gilli,Sabrina; Rodrigues,Rosângela; Brigido,Luis Fernando
Fonte: Instituto de Medicina Tropical Publicador: Instituto de Medicina Tropical
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/2009 EN
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In South Brazil the circulation of two HIV-1 subtypes with different characteristics represents an important scenario for the study of the impact of HIV-1 diversity on the evolution of the HIV-1 epidemic and AIDS disease. HIV-1 B, the predominant variant in industrialized countries and HIV-1 C, the most prevalent subtype in areas with rapid epidemic growth, are implicated in most infections. We evaluated blood samples from 128 antiretroviral (ARV) naïve patients recruited at entry to the largest HIV outpatient service in Porto Alegre. Based on partial pol region sequencing, HIV-1 C was observed in 29%, HIV-1 B in 22.6% and, the recently identified CRF31_BC, in 23.4% of 128 volunteers. Other variants were HIV-1 F in 10% and other mosaics in 5.5%. In order to evaluate the association of socio-behavioral characteristics and HIV-1 subtypes, interviews and laboratory evaluation were performed at entry. Our data suggest an established epidemic of the three major variants, without any evidence of partitioning in either of the subgroups analyzed. However, anal sex practices were associated with subtype B, which could indicate a greater transmissibility of non-B variants by vaginal intercourse. This study provides baseline information for epidemiologic surveillance of the changes of the molecular characteristics of HIV-1 epidemics in this region.

THE INFLUENCE OF HIV-1 SUBTYPES C, CRF31_BC AND B ON DISEASE PROGRESSION AND INITIAL VIROLOGIC RESPONSE TO HAART IN A SOUTHERN BRAZILIAN COHORT

Nunes,Cynara Carvalho; Matte,Maria Cristina Cotta; Dias,Claudia Fontoura; Araújo,Leonardo Augusto Luvison; Guimarães,Luciano Santos Pinto; Almeida,Sabrina; Brígido,Luis Fernando Macedo
Fonte: Instituto de Medicina Tropical Publicador: Instituto de Medicina Tropical
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2014 EN
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Background: Although most HIV-1 infections in Brazil are due to subtype B, Southern Brazil has a high prevalence of subtype C and recombinant forms, such as CRF31_BC. This study assessed the impact of viral diversity on clinical progression in a cohort of newly diagnosed HIV-positive patients. Methods: From July/2004 to December/2005, 135 HIV-infected patients were recruited. The partial pol region was subtyped by phylogeny. A generalized estimating equation (GEE) model was used to examine the relationship between viral subtype, CD4+ T cell count and viral load levels before antiretroviral therapy. Hazard ratio (Cox regression) was used to evaluate factors associated with viral suppression (viral load < 50 copies/mL at six months). Results: Main HIV-1 subtypes included B (29.4%), C (28.2%), and CRF31_BC (23.5%). Subtypes B and C showed a similar trend in CD4+ T cell decline. Comparison of non-B (C and CRF31_BC) and B subtypes revealed no significant difference in the proportion of patients with viral suppression at six months (week 24). Higher CD4+ T cell count and lower viral load were independently associated with viral suppression. Conclusion: No significant differences were found between subtypes; however, lower viral load and higher CD4+ T cell count before therapy were associated with better response.

Human immunodeficiency virus type 1 (HIV-1) genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy

Couto-Fernandez,JC; Silva-de-Jesus,C; Veloso,VG; Rachid,M; Gracie,RSG; Chequer-Fernandez,SL; Oliveira,SM; Arakaki-Sanchez,D; Chequer,PJN; Morgado,MG
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/2005 EN
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In order to assess the human immunodeficiency virus type 1 (HIV-1) drug resistance mutation profiles and evaluate the distribution of the genetic subtypes in the state of Rio de Janeiro, Brazil, blood samples from 547 HIV-1 infected patients failing antiretroviral (ARV) therapy, were collected during the years 2002 and 2003 to perform the viral resistance genotyping at the Renageno Laboratory from Rio de Janeiro (Oswaldo Cruz Foundation). Viral resistance genotyping was performed using ViroSeqTM Genotyping System (Celera Diagnostic-Abbott, US). The HIV-1 subtyping based on polymerase (pol) gene sequences (protease and reverse transcriptase-RT regions) was as follows: subtype B (91.2%), subtype F (4.9%), and B/F viral recombinant forms (3.3%). The subtype C was identified in two patients (0.4%) and the recombinant CRF_02/AG virus was found infecting one patient (0.2%). The HIV-1 genotyping profile associated to the reverse transcriptase inhibitors has shown a high frequency of the M184V mutation followed by the timidine-associated mutations. The K103N mutation was the most prevalent to the non-nucleoside RT inhibitor and the resistance associated to protease inhibitor showed the minor mutations L63P, L10F/R, and A71V as the more prevalent. A large proportion of subtype B was observed in HIV-1 treated patients from Rio de Janeiro. In addition...

HIV-1 subtypes among intravenous drug users from two neighboring cities in São Paulo State, Brazil

Rossini,M.A.A.; Diaz,R.S.; Caseiro,M.; Turcato,G.; Accetturi,C.A.; Sabino,E.C.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2001 EN
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In order to assess the molecular epidemiology of HIV-1 in two neighboring cities located near the epicenter of the HIV-1 epidemics in Brazil (Santos and São Paulo), we investigated 83 HIV-1 strains obtained from samples collected in 1995 from intravenous drug users. The V3 through V5 region of the envelope of gp 120 was analyzed by heteroduplex mobility analysis. Of the 95 samples, 12 (12.6%) were PCR negative (6 samples from each group); low DNA concentration was the reason for non-amplification in half of these cases. Of the 42 typed cases from São Paulo, 34 (81%, 95% confidence limits 74.9 to 87.0%) were B and 8 (19%, 95% confidence limits 12.9 to 25.0%) were F, whereas of the 41 typed cases from Santos, 39 (95%, 95% confidence limits 91.6 to 98.4%) were B and 2 (5%, 95% confidence limits 1.6 to 8.4%) were C. We therefore confirm the relationship between clade F and intravenous drug use in São Paulo, and the presence of clade C in Santos. The fact that different genetic subtypes of HIV-1 are co-circulating indicates a need for continuous surveillance for these subtypes as well as for recombinant viruses in Brazil.

HIV subtype, epidemiological and mutational correlations in patients from Paraná, Brazil

Silva,Monica Maria Gomes da; Telles,Flavio Queiroz; Cunha,Clovis Arns da; Rhame,Frank S
Fonte: Brazilian Society of Infectious Diseases Publicador: Brazilian Society of Infectious Diseases
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/10/2010 EN
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OBJECTIVE: Analyze patients with HIV infection from Curitiba, Paraná, their epidemiological characteristics and HIV RAM. METHODS: Patients regularly followed in an ID Clinic had their medical data evaluated and cases of virological failure were analyzed with genotypic report. RESULTS: Patients with complete medical charts were selected (n = 191). Demographic and clinical characteristics were compared. One hundred thirty two patients presented with subtype B infection (69.1%), 41 subtype C (21.5%), 10 subtype F (5.2%), 7 BF (3.7%) and 1 CF (0.5%). Patients with subtype B infection had been diagnosed earlier than patients with subtype non-B. Also, subtype B infection was more frequent in men who have sex with men, while non-B subtypes occurred more frequently in heterosexuals and women. Patients with previous history of three classes of ARVs (n = 161) intake were selected to evaluate resistance. For RT inhibitors, 41L and 210W were more frequently observed in subtype B than in non-B strains. No differences between subtypes and mutations were observed to NNTRIs. Mutations at 10, 32 and 63 position of protease were more observed in subtype B viruses than non-B, while positions 20 and 36 of showed more amino acid substitutions in subtype non-B viruses. Patients with history of NFV intake were evaluated to resistance pathway. The 90M pathway was more frequent in subtypes B and non-B. Mutations previously reported as common in non-B viruses...

Resistance-Associated Mutations to Etravirine (TMC-125) in Antiretroviral-Naïve Patients Infected with Non-B HIV-1 Subtypes▿

Maïga, Almoustapha Issiaka; Descamps, Diane; Morand-Joubert, Laurence; Malet, Isabelle; Derache, Anne; Cisse, Mamadou; Koita, Victoria; Akonde, Alain; Diarra, Bah; Wirden, Marc; Tounkara, Anatole; Verlinden, Yvan; Katlama, Christine; Costagliola, Dominiq
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
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Susceptibility to etravirine (ETR), an expanded-spectrum nonnucleoside reverse transcriptase inhibitor (NNRTI), is dependent on the type and number of NNRTI resistance-associated mutations (RAMs). Studies have shown that some HIV-1 subtypes may have natural polymorphisms described as ETR RAMs. This study addresses the prevalence of ETR RAMs in treatment-naïve patients infected with HIV-1 non-B subtypes and its potential impact on ETR susceptibility. The prevalence of ETR RAMs in 726 antiretroviral-naïve patients infected with non-B HIV-1 subtypes was studied. ETR genotypic resistance was interpreted according to Agence Nationale de Recherches sur le SIDA and Stanford algorithms. NNRTI phenotypic susceptibilities of samples with at least one ETR RAM were measured. Overall, 75 (10.3%) of 726 sequences harbored at least one ETR RAM: sequences from 72 patients (10%) each had one ETR RAM, and sequences from 3 patients (0.4%) each had two ETR RAMs (V90I and Y181C in one case and V90I and A98G in two cases). None of the viruses had three or more ETR RAMs, and none were consequently classified as resistant to ETR. All sequences with two ETR RAMs belonged to subtype CRF02_AG. The presence of one ETR RAM was statistically more frequent in subtype CRF02_AG than in other non-B subtypes (P = 0.004). Three new mutation profiles (E138A and V179I...

Sequencing and Phylogenetic Analysis of Near Full-Length HIV-1 Subtypes A, B, G and Unique Recombinant AC and AD Viral Strains Identified in South Africa

Wilkinson, Eduan; Holzmayer, Vera; Jacobs, Graeme B.; de Oliveira, Tulio; Brennan, Catherine A.; Hackett, John; van Rensburg, Estrelita Janse; Engelbrecht, Susan
Fonte: Mary Ann Liebert, Inc. Publicador: Mary Ann Liebert, Inc.
Tipo: Artigo de Revista Científica
Publicado em 01/04/2015 EN
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By the end of 2012, more than 6.1 million people were infected with HIV-1 in South Africa. Subtype C was responsible for the majority of these infections and more than 300 near full-length genomes (NFLGs) have been published. Currently very few non-subtype C isolates have been identified and characterized within the country, particularly full genome non-C isolates. Seven patients from the Tygerberg Virology (TV) cohort were previously identified as possible non-C subtypes and were selected for further analyses. RNA was isolated from five individuals (TV047, TV096, TV101, TV218, and TV546) and DNA from TV016 and TV1057. The NFLGs of these samples were amplified in overlapping fragments and sequenced. Online subtyping tools REGA version 3 and jpHMM were used to screen for subtypes and recombinants. Maximum likelihood (ML) phylogenetic analysis (phyML) was used to infer subtypes and SimPlot was used to confirm possible intersubtype recombinants. We identified three subtype B (TV016, TV047, and TV1057) isolates, one subtype A1 (TV096), one subtype G (TV546), one unique AD (TV101), and one unique AC (TV218) recombinant form. This is the first NFLG of subtype G that has been described in South Africa. The subtype B sequences described also increased the NFLG subtype B sequences in Africa from three to six. There is a need for more NFLG sequences...

Resistência natural ao T-20 em gestantes infectadas pelo HIV-1 do estado de Goiás; Natural resistance to T-20 among pregnant women infected with HIV-1 from central western Brazil

Reis, Mônica Nogueira da Guarda
Fonte: Universidade Federal de Goiás; Brasil; UFG; Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP); Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG) Publicador: Universidade Federal de Goiás; Brasil; UFG; Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP); Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
Tipo: Dissertação Formato: application/pdf
POR
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Among pregnant women infected with HIV-1, drug resistance mutations to antiretroviral drugs (ARV) represent a challenge for the prevention to HIV-1 mother-to child-transmission (MTCT) and for future maternal treatment options. The goal of this study was to assess the presence of mutations in gp41 associated with natural resistance to the fusion inhibitor T-20, polymorphisms and HIV-1 subtypes among pregnant women never treated with T-20 and under different exposure levels to other ARV. A total of 153 pregnant women infected with HIV-1 (ARV naive, under MTCT prophylaxis or under ARV treatment/HAART) was recruited from june/2008-june/2010. The env gene gp41 fragment of 766 bp (FP, HR1, HR2, TM regions) was amplified by “nested”-PCR from cDNA and sequenced among 110 patients (Big Dye Terminator Sequencing v. 3.1, Applied Biosystems, EUA; ABI Prism 3130). HIV-1 subtypes were assigned by REGA tool and by phylogenetic analyses (Neighbor-Joining, Kimura 2-P). T-20 resistance mutations were analyzed according to the IAS/USA, Stanford online HIV Drug Resistance Database and other sources. The median age of pregnant women (n=110) was 26 years (16-42 years), 16% were AIDS cases. The frequency of natural resistance (N42D, L44M and R46M) to T-20 was 5.4% (6/110). All resistance mutations were identified in HIV-1 subtype B isolates within the HR1 region of the gp41 fragment. The prevalence of compensatory mutations in HR2 region of gp41 was 20.9% (23/110): S138A (n=11)...

Resistência transmitida a antirretrovirais e diversidade genética do HIV-1 em pacientes dos estados do Maranhão e do Piauí; HIV-1 transmitted drug resistance and genetic diversity among patients from Maranhão and Piauí States

Moura, Maria Edileuza Soares
Fonte: Universidade Federal de Goiás; Brasil; UFG; Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP); Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG) Publicador: Universidade Federal de Goiás; Brasil; UFG; Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP); Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
Tipo: Tese de Doutorado Formato: application/pdf
POR
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In a vast country, like Brazil surveillance of transmitted drug resistance to antiretroviral drugs/TDR should be continuous and extended to different locations and exposure groups. In the last decade significant geographic differences have been reported in the Brazilian AIDS epidemic: reduction in incidence of AIDS cases and related mortality in the southeast region (epicenter of the epidemic) contrasting with significant rise in both parameters in the northeast region. This study describes TDR and HIV-1 subtypes in protease-PR and reverse transcriptase-RT regions among antiretroviral (ARV) naïve patients from Piauí State (n=89) and Maranhão State (n=106), northeast, Brazil recruited between August 2011 and June 2012. HIV-1 pol gene (protease/PR and 2/3 of reverse transcriptase/RT) was sequenced from RNA. TDR was evaluated using the Calibrated Population Resistance (CPR) tool/Stanford HIV-1 Database, HIV-1 subtypes were defined by REGA software and phylogenetic analyses. Among patients from Piauí State (44 females, 45 males, 22 of them were men who have sex with men-MSM), overall TDR rate was 13.5%. TDR rate among MSM was 27.3% while among heterosexual men TDR rate was 10% and 9.1% among females. Single-class mutations to ARV (RT nucleoside and non nucleoside inhibitors NRTI/NNRTI or PR inhibitors/PI) predominated (10/12): M46L/V82F/L90M (PI)...

Étude de la résistance des sous-types non-B du VIH-1 aux antirétroviraux au Mali

Haidara, Alpha
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
FR
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Nous avons effectué ce travail afin d’évaluer l’impact d’une utilisation accrue des antirétroviraux (ARV) sur l’émergence de la résistance dans le cadre d’une cohorte de sujets infectés par le VIH-1, enrôlés au Mali pour recevoir la thérapie antirétrovirale. La première partie de ce travail a évalué la résistance primaire auprès de 101 sujets naïfs aux ARV. Cette étude a démontré que la majorité des sujets (71,3%) étaient infectés par le sous-type CRF02_AG. La prévalence de la résistance primaire était de 9,9%. Ce chiffre dépasse largement la moyenne de 5,5% observée dans les pays en développement et le seuil des 5% fixé par l’OMS dans le cadre de la surveillance de la résistance. Les mutations associées aux analogues de la thymidine ou « Thymidine-associated Mutations » (TAMs): M41L, D67N, L210W, T215A/Y, K219E liées à la résistance aux inhibiteurs nucléosidiques de la transcriptase inverse (INTI) ainsi que les mutations K103N, V108I, V179E et Y181C impliquées dans la résistance aux inhibiteurs non nucléosidiques de la transcriptase inverse (INNTI) étaient majoritairement observées. Ces mutations sont compatibles avec les régimes de traitement de première ligne utilisés au Mali...

HIV non-B subtype distribution: Emerging trends and risk factors for imported and local infections newly diagnosed in South Australia

Hawke, K.; Waddell, R.; Gordon, D.; Ratcliff, R.; Ward, P.; Kaldor, J.
Fonte: Mary Ann Liebert Inc Publ Publicador: Mary Ann Liebert Inc Publ
Tipo: Artigo de Revista Científica
Publicado em //2013 EN
Relevância na Pesquisa
65.86%
Monitoring HIV subtype distribution is important for understanding transmission dynamics. Subtype B has historically been dominant in Australia, but in recent years new clades have appeared. Since 2000, clade data have been collected as part of HIV surveillance in South Australia. The aim of this study was to evaluate the prevalence of and risk factors for HIV-1 non-B subtypes. The study population was composed of newly diagnosed, genotyped HIV subjects in South Australia between 2000 and 2010. We analyzed time trends and subtype patterns in this cohort; notification data were aggregated into three time periods (2000–2003, 2004–2006, and 2007–2010). Main outcome measures were number of new non-B infections by year, exposure route, and other demographic characteristics. There were 513 new HIV diagnoses; 425 had information on subtype. The majority (262/425) were in men who have sex with men (MSM), predominantly subtype B and acquired in Australia. Infections acquired in Australia decreased from 77% (2000–2003) to 64% (2007–2010) (p=0.007) and correspondingly the proportion of subtype B declined from 85% to 68% (p=0.002). Non-B infections were predominantly (83%) heterosexual contacts, mostly acquired overseas (74%). The majority (68%) of non-B patients were born outside of Australia. There was a nonsignificant increase from 1.6% to 4.2% in the proportion of locally transmitted non-B cases (p=0.3). Three non-B subtypes and two circulating recombinant forms (CRFs) were identified: CRF_AE (n=41)...

Molecular epidemiology of HIV-1 circulating among injecting drug users in the great Lisbon

Sousa, Carina; Videira e Castro, Sandra; Pádua, Elizabeth; Parreira, Ricardo; Esteves, Aida; Piedade, João
Fonte: IHMT Publicador: IHMT
Tipo: Conferência ou Objeto de Conferência
Publicado em 20/04/2013 ENG
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Molecular epidemiology of HIV-1 circulating among injecting drug users in the Greater Lisbon Carina Sousa1; Sandra Videira e Castro1; Elizabeth Pádua3; Ricardo Parreira1,2; Aida Esteves1,2; João Piedade1,2 1Grupo de Virologia, UEI de Microbiologia Médica; 2Unidade de Parasitologia e Microbiologia Médicas (UPMM) Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa Rua da Junqueira nº100, 1349-008 Lisboa, Portugal 3Laboratório de Referência da Sida, Instituto Nacional de Saúde Dr. Ricardo Jorge Avenida Padre Cruz, 1649-016 Lisboa, Portugal Background and Objectives HIV/AIDS is recognized as a public health problem partly because of the high degree of viral genetic diversity that poses a major challenge for diagnosis, prevention by vaccination and treatment. Human immunodeficiency virus type 1 (HIV-1) genetic variants are classified in 4 phylogenetic groups: M, N, O and P. Group M, responsible for the great majority of HIV-1 infections worldwide, can be further subdivided into 9 phylogenetic subtypes (A–D, F–H, J and K) and, at least, 6 sub-subtypes (A1–A4 and F1–F2). Genetic recombination events, during infection with multiple subtypes, continuously give rise to mosaic viruses (unique recombinant forms...

Molecular epidemiology of HIV type 1 infection in Portugal: high prevalence of non-B subtypes

Esteves, A; Parreira, R; Venenno, T; Franco, M; Piedade, J; Sousa, JG; Canas-Ferreira, W
Fonte: Mary Ann Liebert Publicador: Mary Ann Liebert
Tipo: Artigo de Revista Científica
Publicado em //2002 ENG
Relevância na Pesquisa
65.88%
In this study, we have investigated the diversity of current HIV-1 strains circulating in the metropolitan area of Lisbon, Portugal. A total of 217 HIV-1-positive blood samples, collected between October 1998 and December 2000, was genetically characterized in the gp120 C2V3C3 region (n = 205) or part of the gp41 N-terminal segment (n = 12) by heteroduplex mobility assay (HMA) and/or DNA sequencing. The HMA subtyping efficiency (number of samples unambiguously subtyped by HMA divided by the total number of samples subtyped) was 65.9% (143 of 217), with indeterminate migration patterns of subtype A and G strains contributing significantly to this value. On the overall, subtype B was the most prevalent (50.2%), followed by subtypes G (21.7%), A (17.5%), and F (5.5%), whereas subtypes C, D, H, and J accounted altogether for 5.1% of the infections. Non-B subtypes were responsible for 77.4 and 33.1% of the infections among African immigrants and Portuguese subjects, respectively. Angolan individuals (n = 25) were the only ones infected with all the HIV-1 subtypes documented, probably reflecting a high degree of viral genetic diversification in their country of origin. Phylogenetic analysis showed a predominance of IbNG-like viruses among subtype A sequences and two new major subclusters within subtype G (G(P) and G(P)'). The majority of the Portuguese G sequences described formed a well-defined subcluster (G(P))...

Subtype AE HIV-1 DNA and recombinant Fowlpoxvirus vaccines encoding five shared HIV-1 genes: safety and T cell immunogenicity in macaques

De Rose, Robert; Chea, Socheata; Dale, C Jane; Reece, Jeanette; Fernandez, Caroline S; Wilson, Kim M; Thomson, Scott; Ramshaw, Ian; Coupar, Barbara E H; Boyle, David B; Sullivan, Mark T; Kent, Stephen J
Fonte: Elsevier Publicador: Elsevier
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
85.67%
To induce broad T cell immunity to HIV-1, we evaluated the safety, immunogenicity and dose-response relationship of DNA and recombinant Fowlpoxvirus (rFPV) vaccines encoding five shared HIV subtype AE genes (Gag, Pol, Env, Tat, Rev) in pigtail macaques. The DNA (three doses of either 1 mg or 4.5 mg) and rFPV (a single boost of either 5 × 107 or 2 × 108 plaque forming units) vaccines were administered intramuscularly without adjuvants. Broadly reactive HIV-specific T cell immunity was stimulated by all doses of the vaccines administered, without significant differences between the high and low doses studied. The vaccines induced both CD4 and CD8 T cell responses to Gag, Pol, Env and Tat/Rev proteins, with CD4 T cell responses being greater in magnitude than CD8 T cell responses. The vaccine-induced T cell responses had significant cross-recognition of heterologous HIV-1 proteins from non-AE HIV-1 subtypes. In conclusion, these subtype AE HIV-1 DNA and rFPV vaccines were safe, induced broad T-cell immunity in macaques, and are suitable for progression into clinical trials.

A influência dos subtipos C, CRF31_BC e B do vírus HIV-1 na progressão da infecção e resposta virológica inicial a terapia antirretroviral em uma coorte no sul do Brasil; THE INFLUENCE OF HIV-1 SUBTYPES C, CRF31_BC AND B ON DISEASE PROGRESSION AND INITIAL VIROLOGIC RESPONSE TO HAART IN A SOUTHERN BRAZILIAN COHORT

Nunes, Cynara Carvalho; Matte, Maria Cristina Cotta; Dias, Claudia Fontoura; Araújo, Leonardo Augusto Luvison; Guimarães, Luciano Santos Pinto; Almeida, Sabrina; Brígido, Luis Fernando Macedo
Fonte: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo Publicador: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; Formato: application/pdf
Publicado em 01/06/2014 ENG
Relevância na Pesquisa
75.88%
Introdução: Embora a maioria das infecções de HIV-1 no Brasil seja devido ao subtipo B, o Sul do Brasil apresenta uma alta prevalência do subtipo C e formas recombinantes, como CRF31_BC. Este estudo avaliou o impacto da diversidade viral na evolução clínica em uma coorte de pacientes HIV-positivos recém diagnosticados. Métodos: De julho/2004 a dezembro/2005, 135 pacientes anti-HIV reagentes foram recrutados. A região pol parcial foi subtipada por filogenia. Um modelo de equação de estimativa generalizada (GEE) foi utilizado para examinar a relação entre subtipo viral, contagem de células CD4 e níveis de carga viral pré-terapia antirretroviral. Hazard ratio (regressão de Cox) foi utilizada para avaliar os fatores associados à supressão viral (carga viral < 50 cópias/mL em seis meses). Resultados: Os principais subtipos de HIV-1 incluíram B (29,4%), C (28,2%) e CRF31_BC (23,5%). Os subtipos B e C apresentaram uma tendência semelhante no declínio de células CD4. Quando comparados os subtipos não B (C e CRF31_BC) e B, não houve diferença significativa na proporção de pacientes com supressão viral aos seis meses (24 semanas). CD4 mais alto e carga viral mais baixa demonstraram associação independente com supressão viral. Conclusão: Não houve diferença significativa entre os subtipos; entretanto...

Alta prevalência e associação do subtipo não-B do vírus HIV-1 com risco específico de transmissão sexual entre pacientes virgens de tratamento antirretroviral em Porto Alegre, Brasil; High prevalence and association of HIV-1 non-B subtype with specific sexual transmission risk among antiretroviral naïve patients in Porto Alegre, RS, Brazil

Dias, Cláudia Fontoura; Nunes, Cynara Carvalho; Freitas, Isabela Osório; Lamego, Isabel Saraiva; Oliveira, Ilda Maria Rodrigues de; Gilli, Sabrina; Rodrigues, Rosângela; Brigido, Luis Fernando
Fonte: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo Publicador: Universidade de São Paulo. Instituto de Medicina Tropical de São Paulo
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; Formato: application/pdf
Publicado em 01/08/2009 ENG
Relevância na Pesquisa
85.9%
No sul do Brasil a circulação de dois subtipos de HIV-1 com características diferentes representa importante cenário para o estudo do impacto da diversidade do HIV-1 na evolução da epidemia e na AIDS. O HIV-1 B, variante predominante nos países industrializados e o HIV-1 C, o subtipo mais prevalente em áreas com maiores taxas de crescimento da epidemia, estão implicados na maioria das infecções. Avaliamos amostras de sangue de 128 pacientes sem exposição a antirretrovirais, recrutados ao ingressarem no maior serviço ambulatorial de HIV/AIDS de Porto Alegre. Com base no sequenciamento parcial da região pol, o HIV-1 C foi observado em 29%, HIV-1 B em 22,6% e uma forma recombinante recentemente descrita, CRF31_BC, foi observada em 23,4% entre 128 voluntários. Outras variantes encontradas foram HIV-1 F em 10% e outros mosaicos em 5,5%. Para avaliar associações entre características sócio-comportamentais e subtipos do HIV-1 foram realizadas entrevistas e exames laboratoriais na entrada do estudo. Nossos dados sugerem uma epidemia estabelecida dessas três variantes principais, sem evidência de compartilhamento em nenhum subgrupo analisado. Entretanto, prática sexual anal se mostrou associada à transmissão de subtipo B...