Dendritic Cell-Based Immunotherapies to Fight HIV: How Far from a Success Story? A Systematic Review and Meta-Analysis.

The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%-51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies.

Mannose binding lectin and mannose binding lectin-associated serine protease-2 genes polymorphisms in human T-lymphotropic virus infection.

Variations in genes involved in the immune response pathways may influence the interaction between viruses (such as Human T-lymphotropic virus, HTLV-1) and the host. The mannose binding lectin (MBL) and its associated serine protease type 2 (MASP-2) promote the activation of the lectin pathway of the complement system. As the interaction of complement system with HTLV-1 is not well understood, the MBL2 promoter/exon 1 polymorphisms and a MASP2 missense polymorphism were examined in a Northeast Brazilian population, looking for a possible relationship between these variations and the susceptibility to HTLV-1 infection. The present study describes an association between a polymorphism in the MASP2 gene and susceptibility to HTLV-1 infection, and provides further evidence of an association between the MBL2 gene and HTLV-1 infection. These findings suggest an important role of the complement system activation, via the lectin pathway, in the susceptibility to HTLV-1 infection.

High polymorphism of the MBL2 gene in patients with atopic dermatitis.

BACKGROUND: Low serum levels of mannose-binding lectin (MBL) are determined mainly by variant alleles of the MBL2 gene and it has been suggested that MBL may play a role in the susceptibility to atopic dermatitis (AD). OBJECTIVE: The aim was to investigate the difference of the frequency of MBL2 variant alleles in AD patients and in a group of individuals without AD, and associate the MBL2 alleles with AD severity. METHODS: MBL2 variant allele's frequency was investigated in 131 children with AD and 165 healthy children/adolescents matched by convenience. The severity of disease was graded according to the SCORing Atopic Dermatitis (SCORAD) index. The first exon variants were called "O" and the wild type "A". The variants in the promoter were H/L at -550 and X/Y at -221, determined by Real Time PCR. RESULTS: Children with AD had higher frequency of allele O and the genotypes related to low or deficient levels of MBL, when compared to the healthy group (p = 0.0012 and p < 0.001, respectively), but not with AD severity. CONCLUSION: Low or deficient MBL serum levels determined genetically may contribute to the predisposition for AD, but not for disease severity.

Frequency of primary resistance to antiretroviral drugs and genetic variability of HIV-1 among infected pregnant women recently diagnosed in Luanda-Angola.

The determination of the prevalence of primary resistance to antiretroviral therapy in different places of the world is of extreme importance in molecular epidemiology monitoring, and it can guide the initial patient therapy in a given geographical area. The frequency of drug resistance mutations (DRM) and the genetic variability of HIV-1 isolates from newly diagnosed HIV-infected pregnant women attending the antenatal clinics of the Lucrecia Paim and Augusto N'Gangula maternities, Luanda-Angola, were determined. Thirty five out of 57 samples (61.4%) were sequenced and one mutation associated with resistance to nucleoside reverse transcriptase inhibitors was detected. Additionally, two mutations associated with resistance to non-nucleoside reverse transcriptase inhibitors were also detected. No primary mutations associated with protease inhibitors (PI) were found. Subtypes A1, C, D, F1, G, H, CRF 13, CRF 37, and other mosaics were detected.

[Human papillomavirus cervical infection: viral genotyping and risk factors for high-grade squamous intraepithelial lesion and cervix cancer]. / Infecção cervical por papilomavírus humano: genotipagem viral e fatores de risco para lesão intraepitelial de alto grau e câncer de colo do útero.

PURPOSE: to analyze the characteristics of viral infection and the risk factors for high-grade squamous intraepithelial lesion and cervical carcinoma in women with cervical HPV infection. METHODS: a case-control study was conducted on women with cervical HPV at a Gynecology reference service enrolled at the Public Health System, located in Recife, Northeastern Brazil. The groups of cases (72 women with high-grade squamous intraepithelial lesion or cervical cancer) and controls (176 women with normal Pap smear or benign alterations) were investigated for six viral genotypes (HPV 16, 18, 31, 33, 6, 11) in ecto- and endocervical material using MY09/MY11 primers. The independent variables were ranked in three levels of determination: distal (sociodemographic), intermediate (behavioral) and proximal (previous Pap smear). The homogeneity of proportions was tested (χ2), unadjusted Odds Ratios (OR) were obtained and hierarchical logistic regression was applied to the final model, with adjustment of the effect of each variable to the outcome based on the variables in the same and previous levels of causality. RESULTS: the viral genotype of cervical infection was identified in 76.6% of the 248 women participating in the study. High-risk HPV genotypes (83.4% of cases and 67.1% of controls) were predominant, especially HPV 16 and 31. The distal risk factors identified were: living in a rural area (OR=2.71, 95%CI: 1.18-6.23), less than three years of study (OR=3.97, 95%CI: 2.09-7.54) and family income below two minimum wages (OR=3.30, 95%CI: 1.04-10.51); intermediate: four or more pregnancies (OR=2.00, 95%CI: 1.06-3.76); and proximal: absence of a previous Pap smear (OR=9.74, 95%CI: 2.48-38.28). CONCLUSIONS: genotypes 16 and 31 of cervical HPV infection are predominant among women assisted by the Public Health System in Northeastern Brazil. Socioeconomic and reproductive factors, as well as the absence of cytological screening, represent risk factors for the progression of infection to high-grade squamous intraepithelial lesion and cervical cancer.

Sensitivity and specificity of BCG scar reading among HIV-infected children.

BCG scar has been used as an indicator of vaccination with BCG in the past, but the validity of scar among HIV-positive children is still unknown. The validity of BCG scar reading among such children was estimated, using three different gold standards. The sensitivity ranged from 81.3% (95%-CI: 78.0-84.2) to 91.6% (95%-CI: 88.4-94.0), when the gold standards were, respectively, information from the adult responsible for the child and the vaccination card. The specificity ranged from 90.5% (95% CI: 81.6-95.5) to 94.1% (95% CI: 87.7-97.4), when the gold standards were, respectively, the vaccination card and information from the adult responsible for the child. Reading of BCG scar was shown to be a good indicator for vaccination in the past, among HIV-infected children.

Multilevel analysis of hepatitis A infection in children and adolescents: a household survey in the Northeast and Central-west regions of Brazil.

BACKGROUND: The objectives were to estimate the prevalence of hepatitis A among children and adolescents from the Northeast and Midwest regions and the Federal District of Brazil and to identify individual-, household- and area-levels factors associated with hepatitis A infection. METHODS: This population-based survey was conducted in 2004-2005 and covered individuals aged between 5 and 19 years. A stratified multistage cluster sampling technique with probability proportional to size was used to select 1937 individuals aged between 5 and 19 years living in the Federal capital and in the State capitals of 12 states in the study regions. The sample was stratified according to age (5-9 and 10- to 19-years-old) and capital within each region. Individual- and household-level data were collected by interview at the home of the individual. Variables related to the area were retrieved from census tract data. The outcome was total antibodies to hepatitis A virus detected using commercial EIA. The age distribution of the susceptible population was estimated using a simple catalytic model. The associations between HAV infection and independent variables were assessed using the odds ratio and corrected for the random design effect and sampling weight. Multilevel analysis was performed by GLLAMM using Stata 9.2. RESULTS: The prevalence of hepatitis A infection in the 5-9 and 10-19 age-group was 41.5 and 57.4%, respectively for the Northeast, 32.3 and 56.0%, respectively for the Midwest and 33.8 and 65.1% for the Federal District. A trend for the prevalence of HAV infection to increase according to age was detected in all sites. By the age of 5, 31.5% of the children had already been infected with HAV in the Northeast region compared with 20.0% in the other sites. By the age of 19 years, seropositivity was approximately 70% in all areas. The curves of susceptible populations differed from one area to another. Multilevel modeling showed that variables relating to different levels of education were associated with HAV infection in all sites. CONCLUSION: The study sites were classified as areas with intermediate endemicity area for hepatitis A infection. Differences in age trends of infection were detected among settings. This multilevel model allowed for quantification of contextual predictors of hepatitis A infection in urban areas.