Showing papers by "Esper G. Kallas published in 2013"

No Evidence of sexual risk compensation in the iPrEx trial of daily oral HIV preexposure prophylaxis

Abstract: Objective Preexposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) reduced HIV acquisition in the iPrEx trial among men who have sex with men and transgender women. Self-reported sexual risk behavior decreased overall, but may be affected by reporting bias. We evaluated potential risk compensation using biomarkers of sexual risk behavior. Design and methods Sexual practices were assessed at baseline and quarterly thereafter; perceived treatment assignment and PrEP efficacy beliefs were assessed at 12 weeks. Among participants with ≥1 follow-up behavioral assessment, sexual behavior, syphilis, and HIV infection were compared by perceived treatment assignment, actual treatment assignment, and perceived PrEP efficacy. Results Overall, acute HIV infection and syphilis decreased during follow-up. Compared with participants believing they were receiving placebo, participants believing they were receiving FTC/TDF reported more receptive anal intercourse partners prior to initiating drug (12.8 vs. 7.7, P = 0.04). Belief in receiving FTC/TDF was not associated with an increase in receptive anal intercourse with no condom (ncRAI) from baseline through follow-up (risk ratio [RR] 0.9, 95% confidence interval [CI]: 0.6–1.4; P = 0.75), nor with a decrease after stopping study drug (RR 0.8, 95% CI: 0.5–1.3; P = 0.46). In the placebo arm, there were trends toward lower HIV incidence among participants believing they were receiving FTC/TDF (incidence rate ratio [IRR] 0.8, 95% CI: 0.4–1.8; P = 0.26) and also believing it was highly effective (IRR 0.5, 95% CI: 0.1–1.7; P = 0.12). Conclusions There was no evidence of sexual risk compensation in iPrEx. Participants believing they were receiving FTC/TDF had more partners prior to initiating drug, suggesting that risk behavior was not a consequence of PrEP use.

IVIg immune reconstitution treatment alleviates the state of persistent immune activation and suppressed CD4 T cell counts in CVID.

Abstract: Common variable immunodeficiency (CVID) is characterized by defective B cell function, impaired antibody production, and increased susceptibility to bacterial infections. Here, we addressed the hypothesis that poor antibody-mediated immune control of infections may result in substantial perturbations in the T cell compartment. Newly diagnosed CVID patients were sampled before, and 6–12 months after, initiation of intravenous immunoglobulin (IVIg) therapy. Treatment-naive CVID patients displayed suppressed CD4 T cell counts and myeloid dendritic cell (mDC) levels, as well as high levels of immune activation in CD8 T cells, CD4 T cells, and invariant natural killer T (iNKT) cells. Expression of co-stimulatory receptors CD80 and CD83 was elevated in mDCs and correlated with T cell activation. Levels of both FoxP3+ T regulatory (Treg) cells and iNKT cells were low, whereas soluble CD14 (sCD14), indicative of monocyte activation, was elevated. Importantly, immune reconstitution treatment with IVIg partially restored the CD4 T cell and mDC compartments. Treatment furthermore reduced the levels of CD8 T cell activation and mDC activation, whereas levels of Treg cells and iNKT cells remained low. Thus, primary deficiency in humoral immunity with impaired control of microbial infections is associated with significant pathological changes in cell-mediated immunity. Furthermore, therapeutic enhancement of humoral immunity with IVIg infusions alleviates several of these defects, indicating a relationship between poor antibody-mediated immune control of infections and the occurrence of abnormalities in the T cell and mDC compartments. These findings help our understanding of the immunopathogenesis of primary immunodeficiency, as well as acquired immunodeficiency caused by HIV-1 infection.

Inter- and Intra-Host Viral Diversity in a Large Seasonal DENV2 Outbreak

Abstract: Background High genetic diversity at both inter- and intra-host level are hallmarks of RNA viruses due to the error-prone nature of their genome replication. Several groups have evaluated the extent of viral variability using different RNA virus deep sequencing methods. Although much of this effort has been dedicated to pathogens that cause chronic infections in humans, few studies investigated arthropod-borne, acute viral infections.

Vaccine-Induced Gag-Specific T Cells Are Associated With Reduced Viremia After HIV-1 Infection

Abstract: The contribution of host T-cell immunity and HLA class I alleles to the control of human immunodeficiency virus (HIV-1) replication in natural infection is widely recognized. We assessed whether vaccine-induced T-cell immunity, or expression of certain HLA alleles, impacted HIV-1 control after infection in the Step MRKAd5/HIV-1 gag/pol/nef study. Vaccine-induced T cells were associated with reduced plasma viremia, with subjects targeting ≥3 gag peptides presenting with half-log lower mean viral loads than subjects without Gag responses. This effect was stronger in participants infected proximal to vaccination and was independent of our observed association of HLA-B*27, -B*57 and -B*58:01 alleles with lower HIV-1 viremia. These findings support the ability of vaccine-induced T-cell responses to influence postinfection outcome and provide a rationale for the generation of T-cell responses by vaccination to reduce viremia if protection from acquisition is not achieved. Clinical trials identifier: NCT00095576.

Microbial Translocation Is Associated with Extensive Immune Activation in Dengue Virus Infected Patients with Severe Disease

Abstract: Background:Severe dengue virus (DENV) disease is associated with extensive immune activation, characterized by a cytokine storm. Previously, elevated lipopolysaccharide (LPS) levels in dengue were found to correlate with clinical disease severity. In the present cross-sectional study we identified markers of microbial translocation and immune activation, which are associated with severe manifestations of DENV infection.Methods:Serum samples from DENV-infected patients were collected during the outbreak in 2010 in the State of Sao Paulo, Brazil. Levels of LPS, lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and IgM and IgG endotoxin core antibodies were determined by ELISA. Thirty cytokines were quantified using a multiplex luminex system. Patients were classified according to the 2009 WHO classification and the occurrence of plasma leakage/shock and hemorrhage. Moreover, a (non-supervised) cluster analysis based on the expression of the quantified cytokines was applied to identify groups of patients with similar cytokine profiles. Markers of microbial translocation were linked to groups with similar clinical disease severity and clusters with similar cytokine profiles.Results:Cluster analysis indicated that LPS levels were significantly increased in patients with a profound pro-inflammatory cytokine profile. LBP and sCD14 showed significantly increased levels in patients with severe disease in the clinical classification and in patients with severe inflammation in the cluster analysis. With both the clinical classification and the cluster analysis, levels of IL-6, IL-8, sIL-2R, MCP-1, RANTES, HGF, G-CSF and EGF were associated with severe disease.Conclusions:The present study provides evidence that both microbial translocation and extensive immune activation occur during severe DENV infection and may play an important role in the pathogenesis.

Skewed Distribution of Natural Killer Cells in Psoriasis Skin Lesions

Abstract: Psoriasis is a hyper-proliferative disease of the skin in which immunological mechanisms play a direct pathogenetic role. There have been limited studies of natural killer (NK) cells in psoriasis. The aim of this study was to examine the phenotype of NK cells in skin biopsies and peripheral blood mononuclear cells from patients with psoriasis and healthy controls. CD56(+) CD16(-) and CD56(+) CD16(+) NK cells were isolated from lesional skin, unaffected skin and PBMC of psoriasis patients, and normal skin and PBMC from healthy controls. The expression of CD57, NKG2A and NKG2C was assessed by flow cytometry. NK cells in psoriasis skin lesions were skewed in their expression of CD57, a marker of NK cell maturity, with CD57 expression significantly reduced and NKG2A expression increased on NK cells in lesional and unaffected skin compared to controls. These data suggest that in this patient cohort, NK cells could be isolated from psoriasis lesions and exhibit an immature phenotype.

CD57 Expression and Cytokine Production by T Cells in Lesional and Unaffected Skin from Patients with Psoriasis

Abstract: Background: The immunopathogenic mechanisms leading to psoriasis remain unresolved. CD57 is a marker of replicative inability and immunosenescence on CD8+ T cells and the proportion of CD57 expressing CD8+ T cells is increased in a number of inflammatory conditions. Methodology: We examined the expression of CD57 on T cells in the skin of patients affected with psoriasis, comparing lesional and unaffected skin. We also assessed functionality of the T cells by evaluating the secretion of several inflammatory cytokines (IL-17A, IFN-gamma, IL-2, IL-33, TNF-alpha, IL-21, IL-22, and IL-27), from cell-sorted purified CD4+ and CD8+ T cells isolated from lesional and unaffected skin biopsies of psoriasis patients. Principal Findings: We observed that the frequency of CD57+CD4+ and CD57+CD8+ T cells was significantly higher in unaffected skin of psoriasis patients compared to lesional skin. Sorted CD4+ T cells from psoriatic lesional skin produced higher levels of IL-17A, IL-22, and IFN-gamma compared to unaffected skin, while sorted CD8+ T cells from lesional skin produced higher levels of IL-17, IL-22, IFN-gamma, TNF-alpha, and IL-2 compared to unaffected skin. Conclusions/Significance: These findings suggest that T cells in unaffected skin from psoriasis patients exhibit a phenotype compatible with replicative inability. As they have a lower replicative capacity, CD57+ T cells are less frequent in lesional tissue due to the high cellular turnover.

Expansion in CD39⁺ CD4⁺ immunoregulatory t cells and rarity of Th17 cells in HTLV-1 infected patients is associated with neurological complications.

Abstract: HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) It is unclear why a minority of infected subjects develops HAM/TSP CD4+ T cells are the main target of infection and play a pivotal role in regulating immunity to HTLV and are hypothesized to participate in the pathogenesis of HAM/TSP The CD39 ectonucleotidase receptor is expressed on CD4+ T cells and based on co-expression with CD25, marks T cells with distinct regulatory (CD39+CD25+) and effector (CD39+CD25−) function Here, we investigated the expression of CD39 on CD4+ T cells from a cohort of HAM/TSP patients, HTLV-1 asymptomatic carriers (AC), and matched uninfected controls The frequency of CD39+ CD4+ T cells was increased in HTLV-1 infected patients, regardless of clinical status More importantly, the proportion of the immunostimulatory CD39+CD25− CD4+ T-cell subset was significantly elevated in HAM/TSP patients as compared to AC and phenotypically had lower levels of the immunoinhibitory receptor, PD-1 We saw no difference in the frequency of CD39+CD25+ regulatory (Treg) cells between AC and HAM/TSP patients However, these cells transition from being anergic to displaying a polyfunctional cytokine response following HTLV-1 infection CD39−CD25+ T cell subsets predominantly secreted the inflammatory cytokine IL-17 We found that HAM/TSP patients had significantly fewer numbers of IL-17 secreting CD4+ T cells compared to uninfected controls Taken together, we show that the expression of CD39 is upregulated on CD4+ T cells HAM/TSP patients This upregulation may play a role in the development of the proinflammatory milieu through pathways both distinct and separate among the different CD39 T cell subsets CD39 upregulation may therefore serve as a surrogate diagnostic marker of progression and could potentially be a target for interventions to reduce the development of HAM/TSP

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

Abstract: 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 Sao 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.

Early immunologic and virologic predictors of clinical HIV-1 disease progression.

Abstract: OBJECTIVE To identify early determinants of HIV-1 disease progression, which could potentially enable individualized patient treatment, and provide correlates of progression applicable as reference phenotypes to evaluate breakthrough infections in vaccine development. DESIGN High-throughput technologies were employed to interrogate multiple parameters on cryopreserved, retrospective peripheral blood mononuclear cell (PBMC) samples from 51 individuals from Sao Paulo, Brazil, obtained within 1 year of diagnosing early Clade B HIV-1 infection. Fast Progressors, Slow Progressors, and Controllers were identified based on a 2-year clinical follow-up. METHODS Phenotypic and functional T-cell parameters were tested by flow cytometry and qPCR to identify potential early determinants of subsequent HIV-1 disease progression. RESULTS Major differences were observed between Controllers and Progressors, especially in cell-associated viral load (CAVL), the differentiation pattern and CD38 expression of CD8 T cells, and the cytokine pattern and activation phenotype of HIV-1-specific CD8 T cells. Despite remarkably few other differences between the two Progressor groups, the CAVL had predictive power independent of plasma viral load. CONCLUSION Analysis of three parameters (% CD38 CD8 T cells, total CAVL, % CCR5 CD8 T cells) was sufficient to predict subsequent disease progression (P < 0.001). Use of such prognostic correlates may be crucial when early CD4 T-cell counts and plasma viral load levels fail to discriminate among groups with differing subsequent clinical progression.

CD4+ T-cell activation impairs serogroup C Neisseria meningitis vaccine response in HIV-infected children.

Abstract: OBJECTIVE To investigate the influence of CD4 T-cell activation and regulatory populations in HIV-infected children antibody response to vaccination with a conjugate C polysaccharide vaccine. DESIGN CD4 T-cell activation was evaluated by expression of CD38, HLA-DR and CCR5 molecules. Regulatory CD4 T cells (TReg) were characterized as FoxP3CD127CD25 and inducer T cells (TInd) as CD4FoxP3CD25CD39. METHODS All patients (n = 36) were HIV-vertically infected, aged 2-17 years-old and were vaccinated with one vaccine injection. Blood samples were obtained before and after immunization to determine bactericidal antibody titers (SBA), CD4 T-cell activation and frequency of TReg and TInd subsets (multiparametric flow cytometry). RESULTS Children not-responding (n = 18) to MenC vaccine expressed higher frequency of activated CD4 T cells (HLA-DRCD38CCR5) than responders (n = 18), both before and after vaccination (P < 0.05). A significant higher frequency of TReg was detected in responders compared with nonresponders (P = 0.0001). We also detected an inverse correlation between CD4DRCD38CCR5 (P = 0.01) or CD4DRCD38 (P = 0.02) T cells and TReg cell frequency after vaccination. CD4 T-cell activation negatively correlated (P = 0.006) with postvaccination SBA titers but a positive correlation (P = 0.0001) was detected between TReg cells and SBA. TReg and TInd subsets were inversely correlated (P = 0.04). CONCLUSION Our findings suggest that higher CD4 T-cell activation leads to poor vaccine response in children living with HIV, which may be associated with a TReg/TInd disequilibrium.

Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods

Abstract: An estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

From trials to the public health: pre-exposure prophylaxis for HIV prevention

Abstract: Two million two hundred thousand adults were newly HIV-infected in 2011, underscoring the urgent need for new, effective ways to prevent incident infections. Recently, the field of HIV prevention has gathered positive results from different strategies, among different populations, and with varying effect sizes, including the treatment of HIV-positive women and men in discordant couples, male circumcision of HIV-negative men in sub-Saharan Africa, a HIV vaccine evaluated in a community-based trial among HIV-negative men and women in Thailand, the use of vaginal gel formulation of TDF for HIV prevention in women in South Africa, pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) or emtricitabine and TDF (TDF-FTC) among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda, and PrEP with TDF-FTC among heterosexual men and women in Africa. Of these interventions, PrEP is an attractive policy because it does not directly interferes with the sexual intercourse, providing people a choice on HIV prevention regardless of cultural, religious, or social harnesses.

Yellow fever vaccine viremia following ablative BM suppression in AML

Abstract: Yellow fever vaccine (YFV) has been used for over 70 years in endemic areas. It is produced from 17D attenuated viral strain and is rarely associated with serious adverse events (SAE), such as anaphylaxis and YFV-associated neurotropic and viscerotropic diseases. Immunosuppressed patients and patients at extremes of age are at higher risk of developing YFV-associated adverse events (AE). The vaccine is not recommended for infants less than six months old or for persons with altered immune status such as thymic disorders, AIDS and immunosuppressive therapies based on a presumed increased risk for YFV-associated SAE. YFV should be deferred in persons with a history of cancer or transplant recipients until immune recovery, as suggested by two reports describing the lack of YFV AE in immune-recovered BM recipients. Mechanisms for YFV-associated neurotropic and viscerotropic diseases are still not completely elucidated. It is likely that immune response may not contain 17D replication, which usually follows the first vaccine dose. Indeed, a low-level viremia has been described in primary recipients, starting 3–7 days after vaccination, persisting for 1–3 days and decreasing as IgM Abs are produced. We report the case of a patient with AML who started chemotherapy just 7 days after yellow fever (YF) vaccination. 17D viral load was monitored by RT-PCR, as well as clinical and laboratory abnormalities. Levels of neutralizing Abs (NA) against 17D were also quantified. The titration of NA against YF was performed at Fiocruz, Rio de Janeiro, using a Plaque Reduction Neutralization Test in serial twofold dilutions starting at 1:5, in 50 mL aliquots of heatinactivated (56 1C for 30 min) serum, in 96-well tissue culture plates. A positive in house monkey serum sample with YF Ab content calibrated by a WHO International Reference Preparation, with 1115 mIU/mL was the reference for each set of tests, and was repeated every 10 samples. After incubation at room temperature for 1 h, a suspension of Vero cells was added and the plates were incubated for 3 h. The medium was then discarded and the cells overlaid with 100 mL of medium containing carboxymethylcellulose. After incubation for 7 days at 37 1C in 5% CO2, cell monolayers were fixed with 10% formalin, stained with 0.04% crystal violet and plaques counted. The mean Ab content at the 50% end point of the standard was calculated through linear regression. The mean titre of the standard sera determined the levels of protection in each sample. Total RNA was extracted from 140mL of plasma using QIAamp RNA Blood Mini Kit (Qiagen, Hilden, Germany) and eluted in 60 mL of elution buffer. cDNA was obtained through a reverse transcriptase reaction using 10 mL of the extracted RNA, 300 ng of random primer (Amersham Biosciences, Piscataway, NJ, USA); 10 U/mL of Super Script TM II reverse transcriptase (Invitrogen, Carlsbad, CA, USA) in a buffer solution with 0.25 U/mL of ribonuclease inhibitor (Invitrogen) and 0.5 mM deoxyribonucleotide triphosphates (Invitrogen), at final volume of 20 mL. The reaction was incubated at 45 1C for 90 min. Five microlitres of cDNA was added to 20mL of TaqMan Master Mix (Applied Biosystems, Foster City, CA, USA) and was amplified by RT-PCR using the following primers and probe: (YF-NS5_F) 50-GCACGG ATGTAACAGACTGAAGA-30; (YF-NS5_R) 50-CCAGGCCGAACCTGTC AT-30 and (YF-NS5Probe) 50-FAM-CGACTGTGTGGTCCGGCCCATC-30TAMRA. The product was amplified using optical detection system layout of BioRad ICycler for 45 cycles at the following settings: 10 min at 95 1C, followed by 45 cycles of 15 s for 94 1C and 60 s for 60 C. An asymptomatic 39 year-old man was diagnosed with AML after routine blood test. BM aspiration demonstrated 76% blasts, urging chemotherapy initiation. He had been vaccinated against YF for the first time 7 days before chemotherapy was started. Detailed clinical and laboratory follow up for possible YFVassociated AE was performed, and 17D viral load was monitored by RT-PCR, daily for the first 19 days after vaccination (Table 1). He remained clinically stable, without any neurological or hepatic abnormalities that could resemble YFV-associated neurotropic or viscerotropic disease. 17D viral load, as measured by RT-PCR, decreased progressively from the first measurement, with undetectable levels on day 16. NA against 17D were measured on day 28 after vaccination, and surprisingly indicated protective levels. This is an unusual case of YF vaccination followed by chemotherapy-induced severe immunosuppression. The 17D viremia was documented for 15 days after vaccination, and was not associated with detectable AE. Surprisingly, protective NA titers were detected 1 month after the vaccine, indicating memory B lymphocytes may have been preserved despite ablative BM suppression. The use of 17D in immunosuppressed patients is a common concern in clinical practice and several points remain unknown. In a recent review, 17D AE in vulnerable populations of children, pregnant women, older persons, HIV positive patients and in individuals taking immunosuppressive medications were described. Although SAE have been identified among older persons and breastfeeding mothers, no change in the current understanding of the risk of 17D SAE could be provided by this comprehensive review. Several inconclusive reports described mutations in 17D that may be associated with SAE. However, a particular strain related to the lack of AE in an immunosuppressed individual has not been described. Host genetic susceptibilities may also have an important role in the development of YFV AE. In previous reports, cases of YFV AE have been associated with high and prolonged 17D viral load, abnormalities in innate immune response and genetic polymorphisms in chemokine receptor CCR5, and its ligand RANTES. Populations of immunosuppressed individuals are likely to increase worldwide, raising concern about the use of live attenuated vaccines and their possible AE. YFV zones have been expanding in recent years in several regions of South America, in order to prevent potential urban outbreaks of the disease. Understanding viral and immune response dynamics following YFV in healthy and immunosuppressed persons is paramount to elucidate the mechanisms for YFV-associated neurotropic and viscerotropic diseases. Moreover, for immunosuppressed patients Bone Marrow Transplantation (2013) 48, 1008–1009 & 2013 Macmillan Publishers Limited All rights reserved 0268-3369/13

HCV viremia drives an increment of CD86 expression by myeloid dendritic cells.

Abstract: The host immune response, including innate and adaptive immunity, plays a critical role in determining the outcome of viral infection. Nevertheless, little is known about the exact reasons for the failure of the host immune system in controlling hepatitis C virus (HCV) infection. Impairment of dendritic cells (DCs) function is probably one of the mechanisms responsible for immune evasion of HCV. In this study, the frequency and phenotype of DCs subsets were analyzed in three groups: HCV-infected individuals who developed viral persistence (1), HCV-infected individuals who spontaneously cleared the virus (2) and HCV-seronegative uninfected subjects (3). The results showed that the frequency of DCs subsets was not statistically significant between groups. Plasmacytoid DCs circulating exhibited an immature phenotype characterized by low expression of CD86. On the other hand, CD86 expression in myeloid DCs was significantly higher in chronic infected individuals compared to healthy controls (P = 0.037). A positive correlation was observed between CD86+ myeloid DC (mDC) and HCV viral load (r = 0.4121, P = 0.0263). These results suggest that HCV did not have an inhibitory effect on mDC maturation and the HCV viremia drives the increase of CD86 expression in mDC. The regulation of DCs maturation and migration lies at the level of intracellular signaling. HCV can activate or block intracellular signaling pathways and alter DC function. In conclusion, the present study suggests that imbalance of DC maturation by the virus represents a mechanism of evasion of the immune system despite the fact that HCV viremia appears to exert a “stimulatory” effect on cell-surface immune phenotype. J Med. Virol. 85:1919–1924, 2013. © 2013 Wiley Periodicals, Inc.

Dados coletados na rotina da Rede Municipal Especializada em DST/Aids de São Paulo utilizados em pesquisa: relato de experiência

Abstract: Com o objetivo de discutir o uso de dados coletados por unidades de saude de DST/AIDS em pesquisas, comparou-se o conteudo e preenchimento de instrumentos de coleta de dados. Observaram-se ausencia de padronizacao, poucas variaveis comuns a todos os formularios e graus de preenchimento diferenciados. 69% dos instrumentos apresentaram completitude superior a 70%. Foram detectadas dificuldades de se obter estatisticas globais, com baixa possibilidade do uso dos dados sem um tratamento previo. E necessaria uma politica de qualidade da informacao, que pode repercutir na melhoria da qualidade da atencao a saude. � �