High Human Herpesvirus 8 (HHV-8) Prevalence, Clinical Correlates and High Incidence among Recently HIV-1-Infected Subjects in Sao Paulo, Brazil

Background: Human herpesvirus 8 (HHV-8) is the etiological agent for Kaposi Sarcoma, which occurs especially in HIV-infected subjects. HHV-8 infection and its clinical correlates have not been well characterized in recently HIV-1-infected subjects, especially men who have sex with men (MSM).Methodology/Principal Findings: We assessed the HHV-8 seroprevalence, clinical correlates, and incidence after one year of follow-up in a cohort of 228 recently HIV-1-infected individuals, of whom 83.6% were MSM, using indirect immunofluorescence assay. the prevalence of HHV-8 infection at the time of cohort enrollment was 25.9% (59/228). in the univariate model, there were significant associations with male gender, black ethnicity, MSM practice, and previous hepatitis B virus and syphilis infections. in the multivariate model we could still demonstrate association with MSM, hepatitis B, and black ethnicity. No differences in mean CD4+ cell counts or HIV viral load according to HHV-8 status were found. in terms of incidence, there were 23/127 (18.1%) seroconversions in the cohort after 1 year.Conclusions: HHV-8 is highly prevalent among recently HIV-1-infected subjects. Correlations with other sexually transmitted infections suggest common transmission routes.Universidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, São Paulo, BrazilWeb 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

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

Description of genotypes of hepatitis B virus in select group of subjects from Assuncion - Paraguay and São Paulo - Brazil

O presente trabalho analisou a infeccao pelo virus da Hepatite B e a distribuicao dos diferentes genotipos em dois grupos de individuos provenientes de Assuncao e São Paulo. Um total de 11492 individuos pertencentes aos grupos de candidatos a doadores de sangue e pacientes submetidos a dialise renal foram pesquisados na presenca do marcador sorologico AgHBs. As amostras positivas (0,47 por cento) e as identificadas como indeterminadas(valores de densidade optica de 1 a 1,9 vezes o valor do nivel de corte) foram analisadas para detectar a presenca do DNA viral pela tecnica de nested PCR com primers especificos para cada genotipo. Pelo metodo utilizado foi possivel amplificar a totalidade das amostras que resultaram positivas na sorologia e as porcentagens de positividade obtidas foram de 0,4 por cento e 0,2 por cento em São Paulo e Assuncao respectivamente. Na analise de genotipagem, observou-se uma distribuicao mais heterogenea no grupo de São Paulo onde foram encontrados os genotipos A (51,2 por cento), D (34,2 por cento) e F (14,6 por cento); em quanto que em Assuncao a distribuicao foi menos variada e os genotipos encontrados foram D(85 por cento) e F (15 por cento). Na populacao de hemodialisados de Assuncao, todos os pacientes apresentaram o genotipo D, sugerindo que a transmissao da infeccao entre eles possa ter acontecido por uma contaminacao ambiental. Os dados obtidos na populacao de doadores de sangue de ambos grupos se correlacionam com as porcentagens de positividade para o AgHBs achados na literatura assim como com as porcentagens maiores na populacao de hemodialisados. Uma pequena proporcao de individuos AgHBs negativos e anti-HBc positivos apresentaram DNA do VHB detectavel por PCR no soro ressaltando a importancia da pesquisa em casos selecionadosBV UNIFESP: Teses e dissertaçõe

GB virus type C infection modulates T-cell activation independently of HIV-1 viral load

Background: Many clinical studies have suggested a beneficial effect of GB virus type C (GBV-C) on the course of HIV-1 infection, but the mechanisms involved in such amelioration are not clear. As recent evidence has implicated cellular activation in HIV-1 pathogenesis, we investigated the effect of GBV-C viremia on T-cell activation in early HIV-1 infection. Methods: Forty-eight recently infected HIV-1 patients (23 GBV-C viremic) were evaluated for T-cell counts, expanded immunophenotyping GBV-C RNA detection, and HIV-1 viral load. Nonparametric univariate and multivariate analyses were carried out to identify variables associated with cellular activation, including GBV-C status, HIV-1 viral load, T lymphocyte counts, and CD38 and chemokine (C-C motif) receptor 5 (CCR5) surface expression. Finding: We not only confirmed the positive correlation between HIV-1 viral load and the percentage of T cells positive for CD38(+)CD8(+) but also observed that GBV-C viremic patients had a lower percentage of T cells positive for CD38(+)CD4(+), CD38(+)CD8(+), CCR5(+)CD4(+), and CCR5(+)CD8(+) compared with HIV-1-infected patients who were not GBV-C viremic. In regression models, GBV-C RNA(+) status was associated with a reduction in the CD38 on CD4(+) or CD8(+) T cells and CCR5(+) on CD8(+) T cells, independent of the HIV-1 viral load or CD4(+) and CD8(+) T-cell counts. These results were also supported by the lower expression of CD69 and CD25 in GBV-C viremic patients. Interpretation: The association between GBV-C replication and lower T-cell activation may be a key mechanism involved in the protection conferred by this virus against HIV-1 disease progression to immunodeficiency in HIV-1-infected patients. (C) 2009 Wolters Kluwer Health | Lippincott Williams & WilkinsBrazilian Program for STD and AIDS, Ministry of Health[914/BRA/3014-UNESCO/Kallas]Sao Paulo City Health Department[2004-0.168.922-7/Kallas]FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[04/15856-9/Diaz]FAPESP Fundacao de Amparo a Pesquisa do Estado de Sao Paulo[05/01072-9/Levi)]Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazilian Ministry of Educatio

Demographic and serologic characteristics of cohort at initial visit.

<p>Demographic and serologic characteristics of cohort at initial visit.</p

Kaplan-Meier survival curves with CD4+ T cell count ≤350 as the outcome.

<p>Legends: green line: HHV-8 negative; blue line: HHV-8 positive green; +: HHV-8 negative censored blue; +: HHV-8 positive censored.</p

Correlates of HHV-8 infection in study cohort.

*<p>OR: odds ratio.</p>**<p>CI: confidence interval.</p