GBV-C/HGV and HIV-1 coinfection

An interesting interaction pattern has been found between HIV-1 and GBV-C/HGV, resulting in protection against progression to AIDS. The mechanisms involved in this interaction remain to be clarified. We examined the current knowledge concerning this coinfection and developed hypotheses to explain its effects. A better understanding of this interaction could result in new concepts, which may lead to new strategies to control HIV-1 replication and progression to AIDS.Federal University of São PauloPró-Sangue FoundationUNIFESPSciEL

Prevalence, Incidence Density, and Genotype Distribution of GB Virus C Infection in a Cohort of Recently HIV-1-Infected Subjects in São Paulo, Brazil

Background: the results of previous studies elsewhere have indicated that GB virus C (GBV-C) infection is frequent in patients infected with the human immunodeficiency virus type 1 (HIV-1) due to similar transmission routes of both viruses. the aim of this study was to determine the prevalence, incidence density and genotypic characteristics of GBV-C in this population.Methodology/Principal Findings: the study population included 233 patients from a cohort primarily comprised of homosexual men recently infected with HIV-1 in São Paulo, Brazil. the presence of GBV-C RNA was determined in plasma samples by reverse transcriptase-nested polymerase chain reaction and quantified by real-time PCR. GBV-C genotypes were determined by direct sequencing. HIV viral load, CD4+ T lymphocyte and CD8+ T lymphocyte count were also tested in all patients. the overall prevalence of GBV-C infection was 0.23 (95% CI: 0.18 to 0.29) in the study group. There was no significant difference between patients with and without GBV-C infection and Glycoprotein E2 antibody presence regarding age, sex, HIV-1 viral load, CD4+ and CD8+ T cell counts and treatment with antiretroviral drugs. An inverse correlation was observed between GBV-C and HIV-1 loads at enrollment and after one year. Also, a positive but not significant correlation was observed between GBV-C load and CD4+ T lymphocyte. Phylogenetic analysis of the GBV-C isolates revealed the presence of genotype 1 and genotype 2, these sub classified into subtype 2a and 2b.Conclusion/Significance: GBV-C infection is common in recently HIV -1 infected patients in São Paulo, Brazil and the predominant genotype is 2b. This study provides the first report of the GBV-C prevalence at the time of diagnosis of HIV-1 and the incidence density of GBV-C infection in one year.Ministry of HealthSão Paulo City Health DepartmentFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ São Paulo, Div Clin Immunol & Allergy, São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilSão Paulo Blood Bank, São Paulo, BrazilUniv São Paulo, Inst Trop Med, São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilMinistry of Health: 914/BRA/3014-UNESCO/KallasSão Paulo City Health Department: 2004-0.168.922-7/KallasFAPESP: 04/15856-9/Diaz, Sabino KallasFAPESP: 05/01072-9/LeviWeb of Scienc

Variability of HIV-1 Genomes among Children and Adolescents from São Paulo, Brazil

Background: Genetic variability is a major feature of the human immunodeficiency virus type 1 (HIV-1) and considered the key factor to frustrating efforts to halt the virus epidemic. in this study, we aimed to investigate the genetic variability of HIV-1 strains among children and adolescents born from 1992 to 2009 in the state of São Paulo, Brazil.Methodology: Plasma and peripheral blood mononuclear cells (PBMC) were collected from 51 HIV-1-positive children and adolescents on ART followed between September 1992 and July 2009. After extraction, the genetic materials were used in a polymerase chain reaction (PCR) to amplify the viral near full length genomes (NFLGs) from 5 overlapped fragments. NFLGs and partial amplicons were directly sequenced and data were phylogenetically inferred.Results: of the 51 samples studied, the NFLGs and partial fragments of HIV-1 from 42 PBMCs and 25 plasma were successfully subtyped. Results based on proviral DNA revealed that 22 (52.4%) patients were infected with subtype B, 16 (38.1%) were infected with BF1 mosaic variants and 4 (9.5%) were infected with sub-subtype F1. All the BF1 recombinants were unique and distinct from any previously identified unique or circulating recombinant forms in South America. Evidence of dual infections was detected in 3 patients coinfected with the same or distinct HIV-1 subtypes. Ten of the 31 (32.2%) and 12 of the 21 (57.1%) subjects with recovered proviral and plasma, respectively, protease sequences were infected with major mutants resistant to protease inhibitors. the V3 sequences of 14 patients with available sequences from PBMC/or plasma were predicted to be R5-tropic virus except for two patients who harbored an X4 strain.Conclusions: the high proportion of HIV-1 BF1 recombinant, coinfection rate and vertical transmission in Brazil merits urgent attention and effective measures to reduce the transmission of HIV among spouses and sex partners.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)National Institutes of HealthUniv São Paulo, Sch Med, Clin & Res Lab LIM 03, São Paulo, BrazilUniv São Paulo, Inst Trop Med, Virol Lab LIM HCFMUSP 52, São Paulo, BrazilUniv Florida, Miller Sch Med, Story Lab 2, Miami, FL USAUniversidade Federal de São Paulo, Paulista Sch Med, Dept Pediat, São Paulo, BrazilUniv São Paulo, Sch Med, Div Clin Immunol & Allergy, São Paulo, BrazilUniv Calif San Francisco, Dept Med, Div Expt Med, San Francisco, CA USAUniversidade Federal de São Paulo, Paulista Sch Med, Dept Pediat, São Paulo, BrazilFAPESP: 2011/09983-1FAPESP: 2009/540055-5FAPESP: 2009/52381-2FAPESP: 2010/05845-0 2004/15856-9FAPESP: 2006/50096-0CAPES: 2571/2009National Institutes of Health: R01 AI060379Web of Scienc

Frequency of subtype B and F1 dual infection in HIV-1 positive, Brazilian men who have sex with men

Introdução: Como varios estudos sobre vacinacao contra HIV estao em progresso, e importante compreender a frequencia na qual ocorrem co/superinfeccoes intra ou intersubtipos em grupos de alto risco. Esse conhecimento auxiliaria no desenvolvimento de programas de prevencao futuros. Nesse estudo transversal, relatamos a frequencia de coinfeccao entre os subtipos B e F1 em uma cohorte clinica de 41 homens que fazem sexo com homens (HSH), recem infectados com HIV-1, em São Paulo, Brasil. Metodologia: O DNA proviral do HIV-1 foi isolado a partir de leucocitos de sangue periferico de sujeitos polimorfonucleares (PMNs), que foram obtidos no momento da inscricao. Cada individuo era conhecidamente infectado por um virus do subtipo B, conforme determinado em estudo anterior. Um pequeno fragmento do gene da integrase (nucleotideo 4255-4478 do HXB2) foi amplificado por PCR utilizando primers especificos para F1. Os resultados da PCR foram confirmados por analise filogenetica. Os dados de carga viral (VL) foram inferidos a partir dos prontuarios de cada paciente. Resultados: Das 41 amostras estudadas, 5 apresentaram DNA proviral do subtipo F1, O que representa uma taxa de 12,2% de coinfeccao. A comparacao entre os valores de carga viral entre os coinfectados e os infectados apenas pelo subtipo B nao foi estatisticamente diferente (p> 0,16). Nos individuos com infeccao dupla a carga viral mediana foi de 5,3 x 104 copias/mL (intervalo de <400 u 12,5 x 104 copias/mL), e nos individuos infectados apenas pelo subtipo B a carga viral mediana foi de 4,3 x 104 copias/mL (intervalo de <400 u 39,9 x 104 copias/mL). Conclusao: Esse estudo indicou que a coinfeccao entre os subtipos B e F1 ocorre com frequencia na populacao de homens que fazem sexo com homens, HIV-1 positivos, como sugerido por um grande numero de virus recombinantes BF1 relatados no Brasil. Na ausencia de uma vacina eficaz contra o HIV-1, o teste para co/superinfeccao e a implantacao de medidas eficazes nos grupos de risco podem ajudar a reduzir a exposicao viral, a transmissao e a recombinacaoBV UNIFESP: Teses e dissertaçõe

Characterization of Partial and Near Full-Length Genomes of HIV-1 Strains Sampled from Recently Infected Individuals in São Paulo, Brazil

Background: Genetic variability is a major feature of human immunodeficiency virus type 1 (HIV-1) and is considered the key factor frustrating efforts to halt the HIV epidemic. A proper understanding of HIV-1 genomic diversity is a fundamental prerequisite for proper epidemiology, genetic diagnosis, and successful drugs and vaccines design. Here, we report on the partial and near full-length genomic (NFLG) variability of HIV-1 isolates from a well-characterized cohort of recently infected patients in Sao Paul, Brazil.Methodology: HIV-1 proviral DNA was extracted from the peripheral blood mononuclear cells of 113 participants. the NFLG and partial fragments were determined by overlapping nested PCR and direct sequencing. the data were phylogenetically analyzed.Results: of the 113 samples (90.3% male; median age 31 years; 79.6% homosexual men) studied, 77 (68.1%) NFLGs and 32 (29.3%) partial fragments were successfully subtyped. of the successfully subtyped sequences, 88 (80.7%) were subtype B sequences, 12 (11%) BF1 recombinants, 3 (2.8%) subtype C sequences, 2 (1.8%) BC recombinants and subclade F1 each, 1 (0.9%) CRF02 AG, and 1 (0.9%) CRF31 BC. Primary drug resistance mutations were observed in 14/101 (13.9%) of samples, with 5.9% being resistant to protease inhibitors and nucleoside reverse transcriptase inhibitors (NRTI) and 4.9% resistant to non-NRTIs. Predictions of viral tropism were determined for 86 individuals. X4 or X4 dual or mixed-tropic viruses (X4/DM) were seen in 26 (30.2%) of subjects. the proportion of X4 viruses in homosexuals was detected in 19/69 (27.5%).Conclusions: Our results confirm the existence of various HIV-1 subtypes circulating in São Paulo, and indicate that subtype B account for the majority of infections. Antiretroviral (ARV) drug resistance is relatively common among recently infected patients. the proportion of X4 viruses in homosexuals was significantly higher than the proportion seen in other study populations.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Fac Med, Div Clin Immunol & Allergy, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Translat Med, São Paulo, BrazilFundacao Pro Sangue, Blood Ctr Sau Paulo, São Paulo, BrazilUniv São Paulo, Dept Infect Dis, São Paulo, BrazilPubl Hlth Dept São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Translat Med, São Paulo, BrazilFAPESP: 04/15856-9FAPESP: 2006/50096-0Web of Scienc

Evaluation of eleven immunochromatographic assays for SARS-CoV-2 detection: investigating the dengue cross-reaction

COVID-19 disease is spread worldwide and diagnostic techniques have been studied in order to contain the pandemic. Immunochromatographic (IC) assays are feasible and a low-cost alternative especially in low and middle-income countries, which lack structure to perform certain diagnostic techniques. Here we evaluate the sensitivity and specificity of eleven different IC tests in 145 serum samples from confirmed cases of COVID-19 using RT-PCR and 100 negative serum samples from blood donors collected in February 2019. We also evaluated the cross-reactivity with dengue using 20 serum samples from patients with confirmed diagnosis for dengue collected in early 2019 through four different tests. We found high sensitivity (92%), specificity (100%) and an almost perfect agreement (Kappa 0.92) of IC assay, especially when we evaluated IgG and IgM combined after 10 days from the onset of symptoms with RT-PCR. However, we detected cross-reactivity between dengue and COVID-19 mainly with IgM antibodies (5 to 20% of cross-reaction) and demonstrated the need for better studies about diagnostic techniques for these diseases

Faster HIV-1 Disease Progression among Brazilian Individuals Recently Infected with CXCR4-Utilizing Strains

Introduction: Primary HIV infection is usually caused by R5 viruses, and there is an association between the emergence of CCXR4-utilizing strains and faster disease progression. We characterized HIV-1 from a cohort of recently infected individuals in Brazil, predicted the virus's co-receptor use based on the env genotype and attempted to correlate virus profiles with disease progression. Methods: A total of 72 recently infected HIV patients were recruited based on the Serologic Testing Algorithm for Recent HIV Seroconversion and were followed every three to four months for up to 78 weeks. The HIV-1 V3 region was characterized by sequencing nine to twelve weeks after enrollment. Disease progression was characterized by CD4+ T-cell count decline to levels consistently below 350 cells/mu L. Results: Twelve out of 72 individuals (17%) were predicted to harbor CXCR4-utilizing strains; a baseline CD4,350 was more frequent among these individuals (p = 0.03). Fifty-seven individuals that were predicted to have CCR5-utilizing viruses and 10 individuals having CXCR4-utilizing strains presented with baseline CD4.350; after 78 weeks, 33 individuals with CCR5 strains and one individual with CXCR4 strains had CD4.350 (p = 0.001). There was no association between CD4 decline and demographic characteristics or HIV-1 subtype. Conclusions: Our findings confirm the presence of strains with higher in vitro pathogenicity during early HIV infection, suggesting that even among recently infected individuals, rapid progression may be a consequence of the early emergence of CXCR4-utilizing strains. Characterizing the HIV-1 V3 region by sequencing may be useful in predicting disease progression and guiding treatment initiation decisions.Brazilian Program for STD and AIDSBrazilian Program for STD and AIDSMinistry of Health [914/BRA/3014-UNESCO/Kallas]Ministry of HealthSao Paulo City Health DepartmentSao Paulo City Health Department [2004-0.168.922-7/Kallas]Fundacao de Amparo a Pesquisa do Estado de Sao PauloFundacao de Amparo a Pesquisa do Estado de Sao Paulo [04/15856-9/Diaz]Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Brazilian Ministry of EducationBrazilian Ministry of Educatio

Lack of evidence to support the association of a single IL28B genotype SNP rs12979860 with the HTLV-1 clinical outcomes and proviral load

Abstract Background The Interleukin 28B (IL28B) rs12979860 polymorphisms was recently reported to be associated with the human T-cell leukemia virus type 1 (HTLV-1) proviral load (PvL) and the development of the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Methods In an attempt to examine this hypothesis, we assessed the association of the rs12979860 genotypes with HTLV-1 PvL levels and clinical status in 112 unrelated Brazilian subjects (81 HTLV-1 asymptomatic carriers, 24 individuals with HAM/TSP and 7 with Adult T cell Leukemia/Lymphoma (ATLL)). Results All 112 samples were successfully genotyped and their PvLs compared. Neither the homozygote TT nor the heterozygote CT mutations nor the combination genotypes (TT/CT) were associated with a greater PvL. We also observed no significant difference in allele distribution between asymptomatic carriers and patients with HTLV-1 associated HAM/TSP. Conclusions Our study failed to support the previously reported positive association between the IL28B rs12979860 polymorphisms and an increased risk of developing HAM/TSP in the Brazilian population.</p