Fernando Samuel Sion

Genotypic and phenotypic evidence of different drug-resistance mutation patterns between B and non-B subtype isolates of human immunodeficiency virus type 1 found in Brazilian patients failing HAART.

We have investigated the phenotypic and genotypic susceptibility of 14 HIV-1 strains isolated from individuals failing HAART therapy to protease inhibitors (PI). Proviral and plasma viral pol gene fragment were amplified, sequenced and subtyped. Nine samples clustered with protease subtype B reference strains and the remaining samples were classified as non-B subtype corresponding to subtype F (n=4) and subtype A (n=1). Although all patients were treated with similar PI drug regimen, the non-B subtype isolates did not present the L90M and I84V mutations and used mainly G48V and V82A/F to achieve drug resistance. A strong cross-resistance phenotype among all four PI was associated with the mutation L90M in the subtype-B isolates, and with G48V and V82A/F in the non-B counterparts. This observation revealed that the non-B viruses tested had specific genotypic characteristics contrasting with the subtype-B isolates.

Testing Genotypic and Phenotypic Resistance in Human Immunodeficiency Virus Type 1 Isolates of Clade B and Other Clades from Children Failing Antiretroviral Therapy

ABSTRACT The emergence of resistance to antiretroviral drugs is a major obstacle to the successful treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients. In this work, we correlate clinical and virological trends such as viral load (VL) and CD4 counts to genotypic and phenotypic antiretroviral (ARV) resistance profiles of HIV-1 isolates from the B and non-B subtypes found in vertically infected children failing ARV therapy. Plasma samples were collected from 52 vertically HIV-1-infected children failing different ARV therapies. Samples underwent HIV-1 pol sequencing and phenotyping and were clustered into subtypes by phylogenetic analysis. Clinical data from each patient were analyzed together with the resistance (genotypic and phenotypic) data obtained. Thirty-five samples were from subtype B, 10 samples were non-B (subtypes A, C, and F), and 7 were mosaic samples. There was no significant difference concerning treatment data between B and non-B clades. Prevalence of known drug resistance mutations revealed slightly significant differences among B and non-B subtypes: L10I, 21 and 64%, K20R, 13 and 43%, M36I, 34 and 100%, L63P, 76 and 36%, A71V/T, 24 and 0%, and V77I, 32 and 0%, respectively, in the protease (0.0001 ≤ P ≤ 0.0886), and D67N, 38 and 8%, K70R, 33 and 0%, R211K, 49 and 85%, and K219Q/E, 31 and 0%, respectively, in the reverse transcriptase (0.0256 ≤ P ≤ 0.0704). Significant differences were found only in secondary resistance mutations and did not reflect significant phenotypic variation between clade B and non-B.

Prevalência da co-infecção HIV-sífilis em um hospital universitário da cidade do Rio de Janeiro no ano de 2005

This was a study on the prevalence of HIV-syphilis coinfection among 830 HIV/AIDS patients who were being followed up as outpatients at a hospital in Rio de Janeiro between January and May 2005. The participants underwent laboratory tests at the venereal disease research laboratory (VDRL) consisting of CD4+/CD8+ cell counts and viral load tests. They answered questions about their sociodemographic characteristics and past medical history of syphilis. The prevalence of syphilis was 2.7% (22 patients) and the ratio between men and women with coinfection was approximately 4:1. Homosexual men were the category most affected. We did not find any association between coinfection and age, schooling and the laboratory parameters tested. Out of the total number of patients with syphilis, 73% (16) reported previous treatment; of these, 14 (88%) were reinfected, while two (12%) underwent inappropriate treatment. The presence of HIV-syphilis coinfection among patients undergoing routine follow-up signals the need to advise them to adopt safe sex practices, during their outpatient visits.

Expression levels of the innate response gene RIG-I and its regulators RNF125 and TRIM25 in HIV-1-infected adult and pediatric individuals.

Objective:TLRs (Toll-like receptors) and RLRs (RIG-I-like receptors) mediate innate immune responses by detecting microorganism invasion. RIG-I activation results in the production of interferon (IFN) type 1 and IFN responsive genes (ISGs). As the ubiquitin ligases RNF125 and TRIM25 are involved in regulating RIG-I function, our aim was to assess whether the levels of these three genes vary between healthy and HIV-infected individuals and whether these levels are related to disease progression. Design:Gene expression analyses for RIG-I, RNF125, and TRIM25 were performed for HIV-infected adults and the childrens peripheral blood mononuclear cells (PBMCs). Methods:Reverse transcription-quantitative PCRs (RT-qPCRs) were performed in order to quantify the expression levels of RIG-I, RNF125 and TRIM25 from PBMCs purified from control or HIV-infected individuals. Results:Controls express higher levels of the three genes when compared to HIV-infected patients. These expressions are clearly distinct between healthy and progressors, and are reproduced in adults and children. In controls, RNF125 is the highest expressed gene, whereas in progressors, RIG-I is either the highest expressed gene or is expressed similarly to RNF125 and TRIM25. Conclusion:A pattern of expression of RIG-I, RNF125, and TRIM25 genes in HIV patients is evident. The high expression of RNF125 in healthy individuals reflects the importance of keeping RIG-I function off, inhibiting unnecessary IFN production. Consistent with this assumption, RNF125 levels are lower in HIV patients and importantly, the RNF125/RIG-I ratio is lower in patients who progress to AIDS. Our results might help to predict disease progression and unveil the role of poorly characterized host genes during HIV infection.

Total serum IgE levels and profile sensitization to dust mites in patients with asthma

Background Atopic asthma occurs in a significant percentage of patients in different age groups and the main sensitizing allergens are dust mites. The aim of this study was to assess the levels of total serum IgE, specific IgE to Dermatophagoides pteronyssinus (Dp) and Blomia tropicalis (Bt) in patients with asthma as well as the influence of gender, age and severity of disease in the total serum IgE levels and in the sensitization to mites.

Profile and prognosis of adolescents and adults with primary immunodeficiencies in the public health service in Brazil

Results 33 patients were analyzed: 55% female, 70% Caucasian, 27% Black, and 3% Asian, with ages between 12 and 64 years (mean = 36.7, SD = 11) and length of follow-up between 1 and 17 years (mean = 8.84, SD = 11.29). The profile and frequency of PIDs was as follows: Predominantly antibody deficiencies (55%), Combined immunodeficiencies less profound than generally severe combined immunodeficiency (18%) Combined immunodeficiencies associated with features or syndromic (15%), Complement deficiencies (9%), and Autoinflammatory disorders (3%). The average time between onset of symptoms and diagnosis of PID ranged between 1 and 28 years (mean = 10.83, SD = 7.07). Compliance with treatment was good in 76% of patients, partial in 12% and 12% of treatment dropout. Survival between the onset of clinical manifestations and the end of the study ranged between 1 and 47 years (mean = 21.52, SD =13.79). Throughout the study period, one patient, with Wiskott-Aldrich syndrome and partial adherence to treatment, died due to septicemia and there were two deaths from cardiovascular disease.

Correlation between asthma control and quality of life in patients with moderate and severe asthma

Background The evaluation of the degree of disease control and quality of life of patients with asthma is a challenge for general practitioners and medical specialists. The aim of this study was to assess the degree of disease control and quality of life in patients with moderate and severe asthma in clinical follow-up of Allergy and Immunology clinic as well as comparatively evaluate two instruments for assessing asthma control, versus quality of life evaluation.

Comparative evaluation of the accuracy of skin tests and measurement of mite-specific IgE in patients with allergic rhinitis.

Background The diagnostic investigation of sensitization to dust mites is performed through measurement of specific IgE and cutaneous immediate hypersensitivity tests. The general aim of this study was to comparatively evaluate the diagnostic accuracy of immediate hypersensitivity skin tests and specific IgE for Dermatophagoides pteronyssinus (Dp) and Blomia tropicalis in patients with allergic rhinitis.

Levels of total serum IgE and specific IgE sensitization profile in patients with atopic dermatitis.

Background Atopic dermatitis is a multifactorial disease associated with elevated production of IgE and sensitization to multiple food and inhalant allergens.The aim of this study was to assess the levels of total serum IgE (IgE) and specific IgE (sp IgE ) for Dermatophagoides pteronyssinus (Dp), Blomia tropicalis (Bt), egg white, casein, alpha-lactalbumin and beta-lactoglobulin in patients with atopic dermatitis (AD); and the influence of gender, age and severity of disease in these parameters.

235 Frequency of Patients With Clinical Manifestations of Allergic Rhinitis without Evidence of Systemic Atopy and Specific ige Sensitization.

Background The diagnosis of allergic rhinitis (AR) is based on clinical manifestations and supported by a positive result for skin prick test (SPT) or serum specific immunoglobulin E (sIgE) antibodies to aeroallergens. Our objective was to investigate the frequency of patients with clinical manifestations of AR without evidence of specific IgE sensitization. Methods We evaluated patients with clinical manifestations suggestive of AR, other causes of rhinitis excluded, aged >5 years and who had total serum IgE and SPT or sIgE to aeroallergens measured. Skin tests were performed with extracts of Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blomia tropicalis and Aspergillus fumigatus (FDA Allergenic) and total serum IgE and sIgE, for the same allergens, by ImmunoCAP (Phadia). Patients were subdivided into groups according to the results profile, and comparatively analyzed for association with asthma, severity of rhinitis and age. Results We evaluated 116 patients (64% female) aged between 5 and 79 years, including 34 children (29%) and 63 (54%) with bronchial asthma. The observed profiles and frequencies were: high IgE levels and positivity in the SPT or sIgE –55%; normal IgE levels and SPT or sIgE positivity –9%; high IgE levels and SPT and sIgE negativity –3 %; normal IgE levels and negativity in the SPT and sIgE –23%. Among patients with normal levels of total serum IgE and no evidence of specific IgE sensitization, 14% had asthma, while in the remainder the prevalence of asthma was 34% (P = 0.0009). There was no statistical significance in the influence of the rhinitis severity and age in the absence of markers of atopy and allergen sensitization. Conclusions We observed a significant number of patients with clinical manifestations of AR, without evidence of systemic atopy and specific IgE sensitization, indicating the importance of careful research of local allergic rhinitis, as well as other causes of chronic rhinitis. Local allergic rhinitis appears to be less frequent in patients with rhinitis and asthma. The observation of 13% of patients with elevated levels of total IgE without specific sensitization implies the possibility of sensitization to aeroallergens which were not investigated, such as occupational allergens.