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The human T-cell lymphotropic virus type I (HTLV-I) may cause HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP), an incapacitating chronic inflammatory disease of the spinal cord. The detection of IgG anti-HTLV-I antibodies in the serum and cerebrospinal fluid (CSF) has been an important parameter for the laboratorial diagnosis of HAM/TSP. OBJECTIVE: critical evaluation of the methods applied to detect the presence and intrathecal production of total antibodies and anti-HTLV-I in the CSF for the diagnosis of HAM/TSP. METHODS: We performed a systematic review of medical articles by using the key words: "cerebrospinal fluid, intrathecal synthesis of antibodies, HTLV-I associated myelopathy, HTLV-I, HAM/TSP". The used databases included: PubMed, Lilacs, Medline and Cochrane Library. RESULTS: A total of 14 articles were selected: five studies were related to the presence of specific IgG antibody in the CSF and nine studied the intrathecal synthesis of total antibodies (IgG or IgG/IgA/IgM) and specific anti-HTLV-I (IgG or IgM). DISCUSSION: The isolated study of the presence of IgG antibody anti-HTLV-I in the CSF does not show the fraction produced in the central nervous system, which represents low specificity (40%) for the diagnosis of HAM/TSP. The demonstration of the intrathecal synthesis of IgG anti-HTLV-I antibodies is more relevant due to its high specificity (89%) and sensibility (83%). According to Reiber & Felgenhauer (1987), the index IgG anti-HTLV-I, which is based on ELISA test with simultaneous CSF and serum analysis, stands out from the other methods applied to evaluate the intrathecal synthesis of specific antibody. Other studies use small samples and do not demonstrate the sensibility and specificity of the test in the CSF. Only one study shows statistical analysis. CONCLUSION: The immunological diagnosis of the CSF in HAM/TSP requires the standardization of methods, which should be based on tests of high sensibility and specificity.

Shifting of hepatitis A virus (HAV) epidemiology from a high towards an intermediate endemicity pattern and use of antiretroviral therapy increased the risk of HIV/HAV coinfection in developing countries. The aim of this study was to investigate the presence of HAV markers in a cohort of HIV-infected patients from 1988 to 2004. The presence of serum anti-HAV antibodies and HAV-RNA by real-time polymerase chain reaction was investigated in 581 patients. Total anti-HAV antibodies was found in 464/581 (79.8%) patients, however, achanging epidemiologic pattern of hepatitis A among HIV-infected patients from 1988 to 2004 was observed. Among patients susceptible to HAV ( n = 117), 5 (4.2%) were co-infected with HAV, all of them had IgM anti-HAV antibodies and were serum HAV-RNA-positive. The high prevalence of anti-HAV antibodies in HIV-infected patients suggests that screening tests for anti-HAV antibodies should be performed before implementation of hepatitis A vaccination, especially in those patients from endemic countries.

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.

The Brazilian AIDS Program offers free and universal access to antiretroviral therapy. This study investigates the influence of sociodemographic, clinical-prophylactic and therapeutic factors on survival, after AIDS diagnosis, in an open cohort of 1,420 patients assisted in a university hospital in the city of Rio de Janeiro (1995 _ 2002). Kaplan-Meier and Cox proportional hazards models were used to estimate the effect of variables in the three dimensions studied. The overall survival time of the upper quartile was 24 months (CI95%= 20.5-27.5), increasing from 14 months, in 1995, to 46 months, in 1998. We found a protective effect of heterosexual behavior against death that could be attributed to the increasing female-to-male sex ratio in the cohort, which coincided with the time of therapy introduction. Low schooling, hospital admission and lack of follow-up were identified as risk factors for death; PCP and Toxoplasmosis prophylaxis were protective. The number of attempts required to consolidate the antiretroviral therapy showed no significant effect on survival. The full model, which includes the number of antiretroviral drugs in the regimen, confirmed the triple therapy as the best regimen. This study brings important information for designing guidelines to deal with different aspects related to the practical management of patients and their behavior, thus contributing to the success of the program of free access to antiretroviral therapy implemented in Brazil.

Retroviral genomes with a high frequency of G→A mutations are thought to originate during reverse transcription (RT). Here we present a case report of an AIDS patient infected with a subtype F variant where extensive G→A hypermutation (G→A Hypm) sequences were found in the protease gene. This patient was failing HAART at the time the hypermutation was found. These sequences were basically encountered in the proviral compartment on two occasions and were persistently absent in the plasma viral population. The patient's viral genotype showed several mutations related to antiretroviral drug resistance in RT (T69N, M184V, T215F, K219Q) and protease (M36I, G48V, I54V, T63L, V82A) genes. The drug regimen was changed and the viral load dropped 0.9 Logs and CD4 count increased by 200 cells/ml. The hypermutation was not found any more in a 1-year follow up. The patient's wife was infected with a similar virus strain and G→A Hypm sequences were also detected in the RT gene. This is the first report of sexual transmitted G→A Hypermutation in HIV-1 and suggest that this phenomenon can be genetically coded by the viral RT molecule.

Development of drug resistance is the inevitable consequence of incomplete suppression of virus plasma levels in HIV-1-infected patients treated with highly active antiretroviral therapy. Resistance mutations previously characterized have been found in B subtype viruses of developed countries. Moreover, mutation profiles for non-B and more divergent B subtype viruses found in developing countries shall be analyzed together with their ex vivo phenotyping in order to establish an exact correlation between the genotyping data and the clinical management counseling for those uncommon virus subtypes. In the present study, we evaluated the mutation profile for individuals infected with B subtype and non-B subtype viruses. Viral DNA fragments corresponding to the RT gene were amplified, sequenced, and subtyped. Phenotyping analysis for reverse transcriptase nucleoside (NRTI) and nonnucleoside inhibitor susceptibility was performed using the recombinant virus assay technology. Brazilian non-B subtypes (subtype F, n = 4, and subtype A, n = 1) isolates showed essentially the same B subtype mutation profile, presenting an NRTI drug resistance with similar MIC50% and MIC90% values for all drugs analyzed regardless of their subtypes. A strong cross-resistance phenotype among AZT, 3TC, and abacavir could be seen in all isolates analyzed. A novel result was that some RT sequences not only revealed the presence of G333D/E mutations but also correlated to the presence of mutation T386I that could abrogate the M184V-surpassing effect of L210W or L210W plus G333D/E. These findings suggest that Brazilian non-B subtype HIV-1 strains use an identical RT drug resistance mutation pattern when compared to B isolates and will contribute to the validation of the genotypic and phenotypic tests in these predominant worldwide-spread viral variants.

Unusually aggressive forms of cutaneous squamous cell carcinoma are being increasingly recognized as a complication of HIV infection. We report the case of a 59-year-old male patient with advanced HIV infection who presented with a highly aggressive SCC lesion over the scalp area with destruction of the underlying parietal bone and fulminant clinical progression.Formas altamente agressivas de carcinoma cutâneo de células escamosas vêm sendo reconhecidas como uma importante complicação da infecção pelo HIV. Descrevemos o caso de um paciente do sexo masculino, de 59 anos, que se apresentou com uma lesão altamente agressiva de SCC na região do couro cabeludo, com destruição do osso parietal subjacente e curso clínico fulminante.

Unusually aggressive forms of cutaneous squamous cell carcinoma are being increasingly recognized as a complication of HIV infection. We report the case of a 59-year-old male patient with advanced HIV infection who presented with a highly aggressive SCC lesion over the scalp area with destruction of the underlying parietal bone and fulminant clinical progression.

Immune reconstitution inflammatory syndrome (IRIS) in HIV-infected subjects initiating antiretroviral therapy most commonly involves new or worsening manifestations of previously subclinical or overt infectious diseases. Reports of non-infectious IRIS are much less common but represent important diagnostic and treatment challenges. We report on a 34-year-old HIV-infected male patient with no history of gout who developed acute gouty arthritis in a single joint one month after initiating highly active antiretroviral therapy.

The development of paradoxical clinical worsening following initiation of tuberculosis treatment may complicate the clinical course of both HIV-infected and uninfected patients. We report a severe manifestation of the so called paradoxical reaction to the treatment of tuberculosis that unmasked previously silent meningeal disease in a 34-year-old HIV-infected male patient.O desenvolvimento de piora clínica paradoxal como resposta ao início do tratamento da tuberculose pode complicar a evolução de pacientes com e sem infecção pelo HIV. Apresentamos uma grave manifestação da chamada reação paradoxal ao tratamento da tuberculose, que revelou doença meníngea previamente silenciosa em um paciente HIV-positivo de 34 anos.

Mulher de 32 anos infectada pelo HIV 1, vinha utilizando zidovudina/lamivudina 300/150 mg um comprimido duas vezes ao dia e lopinavir/ritonavir 200/50 mg dois comprimidos duas vezes ao dia e profilaxia com sulfametoxazol-trimetoprim 800/160 mg uma vez ao dia, sem profilaxia com macrolídeos. A paciente apresentou enxaqueca severa com prescrição da associação tartarato de ergotamina 1 mg, cafeína 100 mg, paracetamol 220 mg, sulfato de hiosciamina 87,5 mcg, sulfato de atropina 12,5 mcg, dois comprimidos na crise, seguido de um comprimido a cada 30 minutos, com no máximo seis comprimidos ao dia. A paciente ingeriu seis comprimidos em um dia, surgindo uma dor em tornozelo esquerdo três dias depois, que evoluiu para ergotismo e amputação do pé. A 32-year-old female, was diagnosed in 2004 with a C1 HIV1 infection, using zidovudine/lamivudine 300/150 mg BID and lopinavir/ritonavir 400/100 mg BID, in addition to prophylaxis with trimethoprim-sulfamethoxazole 800/160 mg QD, but no prophylaxis with macrolide antibiotics. The patient presented with a severe headache and was prescribed two capsules of the anti-migraine drug Ormigrein™, which contained ergotamine tartrate 1 mg, caffeine 100 mg, paracetamol 220 mg, hyoscyamine sulfate 87.5 mcg, and atropine sulfate 12.5 mcg. Afterwards she was prescribed one capsule of Ormigrein every 30 minutes for a total of six capsules a day. The patient took the medication as prescribed but developed a pain in her left ankle three days later, which evolved to the need for amputation.

A infecção pelo vírus da imunodeficiência humana atinge o Sistema Nervoso Central nos estágios iniciais, causando manifestações neuropsicológicas. Com o objetivo de estudar o desempenho de indivíduos infectados por este vírus em relação às funções cognitivas, foram avaliados 20 pacientes com contagem de linfócitos CD4+ acima de 200 células/mm³, utilizando-se a Escala de Inteligência Wechsler para Adultos. Destes, cinco (25%) eram do sexo masculino e 15 (75%) do sexo feminino, com média de idade de 39,65 desvio-padrão de 10,15 anos. A contagem média de linfócitos CD4+ foi 467,20 desvio-padrão de 215,45 células/mm?. Dentre quatorze pacientes que fizeram uso de terapia antirretroviral de alta atividade foi observado um caso com desempenho das funções cognitivas atenção e aprendizagem muito abaixo da média; os demais (n=13) tiveram desempenho dentro da média. Por meio da Escala de Inteligência Wechsler para Adultos foi possível detectar desempenho abaixo do nível médio do funcionamento cognitivo em indivíduos com resultado positivo para vírus da imunodeficiência humana, mesmo em vigência de terapia antirretroviral de alta atividade. In its early stages, HIV-1 infection involves the Central Nervous System causing neuropsychological manifestations. With the aim of studying the cognitive functions in HIV-1-infected patients, a total of 20 patients infected with HIV-1 with CD4+ lymphocyte count >200 cells/mm³ were studied in accordance with the Wechsler Adult Intelligence Scale (WAIS-III). The present study comprised 20 patients, 5 (25%) male and 15 (75%) female, with a mean age of 39.65 and standard deviation of 10.15 years. The mean CD4+ lymphocyte count was 467.20 with a standard deviation of 215.45 cells/mm³. Amongst the 14 patients who received highly active anti-retroviral therapy (HAART), we noted 1 case in which the performance of the cognitive functions, attention span and learning, was considered to be very low according to WAIS-III, and the remaining (n=13) patients who were treated with HAART demonstrated a performance that was not considered to be outside of the WAIS-III mean. By using WAIS-III testing, it was possible to detect performance of the cognitive functions considered to be very low in HIV-1 infected individuals, even with those receiving HAART.

Objective Multiple sclerosis (MS) is an inflammatory disease characterized by multifocal areas of central nervous system (CNS) demyelination. Activation of coagulation factors and fibrin deposition are observed around CNS blood vessels in experimental autoimmune encephalomyelitis, an animal model of MS. Antithrombin (AT) is a potent anticoagulant with remarkable anti-inflammatory properties, and its inhibitory effects on coagulation and inflammation may play a role in the pathogenesis and clinical course of MS. We studied the association between plasma AT activity and clinical forms of MS. Patients and methods A total of 69 patients, 37 with relapsing–remitting and 32 with secondary progressive MS, were included in the study. A control group (CG) of 34 normal subjects was also studied. Plasma AT activity (Stachrom ATIII) was quantified using a chromogenic activity assay with normal reference values ranging from 70% to 120% of AT activity. Results We found no difference between plasma AT levels in patients and those in CG. We also found no association of AT levels with activity of disease, duration of disease progression, level of neurological disability, and treatment. Conclusion We found no association between plasma AT activity and RRMS or SPMS. It remains to be studied whether exists or not an association between abnormal plasma AT activity and other MS forms.

Methods We conducted a retrospective, longitudinal study evaluating patients with AR, over the age of three, who were using SCIT with extracts of D pteronyssinus (Dp) and/or B tropicalis (Bt) (FDA Allergenic). Data were collected through interviews and medical records. The classification of the severity of adverse reactions met the criteria established by the Allergen Immunotherapy: a Practice Parameter Third Update (2011).

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.

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.

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.

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.

Background CVID comprises a variety of clinical phenotypes that may influence the prognosis of the disease. Our goal was to investigate the clinical phenotypes and prognosis of a series of patients with CVID. Methods We evaluated 11 patients with CVID, according to the PAGID criteria in long-term clinical follow-up (> 10 years). Most patients were on regular use of intravenous immunoglobulin (IVIg), provided free of charge by the government. Clinical evaluation was performed monthly and exams every 6 months to 1 year, including immunological evaluation, hematologic, biochemical, autoimmune, stool, urine analysis, chest CT, abdominal ultrasound and specific investigations of infectious diseases and malignancies, when needed. Results The average follow-up was 21.9 years (12–34). Among the 11 patients, the mean current age was 39.8 years (16 to 62), 73% were female and 82% white. The age at symptoms onset ranged from 4 to 31 years (mean = 18) and diagnosis occurred between ages 11 and 47 (mean = 28). Most patients (55%) had the phenotype of infectious complications only, 27% had infections and immune thrombocytopenic purpura and 18% had infections and solid neoplasias. The most common infections were recurrent sinusitis (100%), pneumonia (82%), giardiasis (36%) and tuberculosis (18%). None of the patients developed lymphoproliferative and / or inflammatory complications. With regard to immunological changes, we observed that 4 patients (36%) experienced an increase in CD8 T lymphocytes and inversion of CD4/CD8 ratio. Adherence to the use of IVIg was good in 50% of patients, fair in 38% and unsatisfactory in 12%. All patients have good quality of life, performing their routine activities of study, work and leisure. Conclusions In the population studied, the most frequent phenotypes were infectious complications or infectious complications + autoimmunity. Tuberculosis can be an important infectious complication in patients with CVID in endemic areas. The delay in the diagnosis of CVID, around 10 years, indicates the need to improve the diagnosis of PID in our country. With proper clinical management and good adherence to the use of IVIg, patients with CVID in developing countries may have survival and quality of life similar to those described in developed countries.

We retrospectively reviewed the effects on the erythrocyte mean corpuscular volume (MCV) of the use of stavudine-including antiretroviral regimens in both zidovudine-naive and zidovudine-experienced HIV-infected patients. Macrocytosis was commonly observed among patients on stavudine-based regimens although the MCV usually stabilized at a lower level than that observed with zidovudine.

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.

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.