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The NCR receptors play a fundamental role in the cytotoxicity mediated by NK cells against tumor cells. In the current study, we investigated possible HIV/AIDS-related changes in the expression of the NCR receptors comparing healthy donors, HIV/AIDS patients, and HIV/AIDS patients with cancer (HIV/AIDSWC). The NCRs were quantified in NK cells (NKdimandNKbright) and T lymphocytes from peripheral blood samples by flow cytometry. We found a significant decrease in the frequency of NK cells expressing NKp46 in HIV/AIDS group (p=0.0012). There was a decrease in the frequency of NK cells expressing NKp46 in the HIV/AIDSWC group; however, this was not statistically significant. We found a significant decrease in the frequency of NK cells expressing NKp30 in the HIV/AIDS group (p=0.0144). There was a decrease in the frequency of NK cells expressing NKp30 and in the HIV/AIDSWC group, but this was not statistically significant. There were no changes in the distribution of NK cells and their subtypes in both groups.

This work aims to elucidate the effects of age and HIV-1 infection on the frequency and function of T cell subsets in response to HIV-specific and non-specific stimuli. As compared with the younger AIDS group, the frequencies of naive and central memory T cells were significantly lower in aged AIDS patients. Although there was also a dramatic loss of classical CD4 + FoxP3 + CD25 + Treg cells in this patient group, high frequencies of IL-10-producing CD4 + FoxP3 − T cells were observed. In our system, the increased production of IL-10 in aged AIDS patients was mainly derived from Env-specific CD4 + FoxP3 − CD152 + T cells. Interestingly, while the blockade of IL-10 activity by monoclonal antibody clearly enhanced the release of IL-6 and IL-1β by Env-stimulated PBMC cultures from aged AIDS patients, this monoclonal antibody enhanced in vitro HIV-1-replication. In conclusion, HIV infection and aging undoubtedly contribute synergistically to a complex immune dysfunction in T cell compartment of HAART-treated older HIV-infected individuals.

The vascular function in HIV-infected persons under HAART and non-HIV-infected persons was investigated.18 HIV-positive patients and 23 HIV-negative subjects (14 younger group and 9 older group) were evaluated for microvascular vasodilatation during postocclusive reactive hyperemia (PORH) and during prolonged local thermal hyperemia; overall microvascular flux increase induced by iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) and large artery stiffness (SI(DVP)).Cutaneous vascular conductance (CVC) responses to ACh were lower in HIV patients compared to both HIV-negative groups (mean [SEM]) (HIV positive: 878.2 [99.5]; older HIV negative: 1129.3 [231.6]; younger HIV negative: 1366.5 [172.6] % baseline). Regarding SNP iontophoresis, HIV-positive and older HIV-negative groups showed lower CVC responses than younger HIV-negative group (HIV positive: 1043.0 [164.6]; older HIV-negative: 980.8 [108.3]; younger HIV-negative: 1757.3 [245.1] % baseline). Vasodilatation induced by thermal hyperemia (HIV positive: 1.63 [0.11]; older HIV negative: 1.48 [0.08]; younger HIV negative: 1.85 [0.27] perfusion units/mm Hg) and PORH (HIV positive: 0.374 [0.025]; older HIV negative: 0.326 [0.025]; younger HIV negative: 0.326 [0.037] PU/mm Hg) were similar between all groups. SIDVP was greater in HIV and older healthy groups than younger healthy group (HIV positive: 9.17 [0.42]; older HIV negative: 8.19 [0.43]; younger HIV negative: 6.42 [0.22] m/s).HIV-infected patients under HAART exhibited slight but nonsignificant lower microvascular reactivity to pharmacological stimuli and increased arterial stiffness compared to age-matched HIV-negative subjects. Comparison of both HIV-positive and older HIV-negative groups with younger HIV-negative subjects suggests that age plays a major role in microvascular reactivity regardless the HIV-infection.

A infeccao pelo HIV e caracterizada pela coexistencia da imunodeficiencia, com deplecao das celulas CD4+ e ativacao cronica sistemica do sistema imune inato e adaptativo. Pacientes com infeccao pelo HIV e/ou AIDS tem o risco elevado de apresentar câncer, sendo o sarcoma de Kaposi (SK) o câncer de maior incidencia e prevalencia em individuos com HIV/AIDS. O objetivo do estudo em questao foi estabelecer a prevalencia de SK em pacientes com AIDS atendidos na Disciplina de Doencas Infecciosas e Parasitarias do HU Pedro Ernesto-UERJ em dois cortes temporais distintos (1985-1994 e 2005-2014). Foram selecionados 81 pacientes com AIDS, adultos de ambos os sexos, com diagnostico de SK. As lesoes de SK foram classificadas como localizadas ou disseminadas. Dos 81 pacientes analisados, a media de idade no momento do diagnostico foi de 36 anos (± desvio-padrao 9,0), com mediana de 34. Quanto ao sexo, dos 81 pacientes, 76 (94%) sao do sexo masculino e cinco (6%) do sexo feminino. O teste estatistico de Mann-Whitney apresentou um p-valor de 0,0029, indicando um maior numero de casos para a decada de 1985 a 1994. O SK na forma disseminada foi predominante em ambos os grupos. Houve uma diminuicao significativa na prevalencia de casos de SK desde o inicio da epidemia do HIV/AIDS ate os dias atuais, provavelmente pelo uso dos antirretrovirais. Houve uma maior frequencia da populacao masculina e de casos de SK na forma disseminada. Descritores: Sindrome de imunodeficiencia adquirida; Sarcoma de Kaposi; Prevalencia. Revista HUPE, Rio de Janeiro, 2015;14(Supl. 1):36-41 doi:10.12957/rhupe.2015.17924

Mutations located in the 109-amino acid fragment of NS5B are typically associated with resistance to interferon (IFN) and ribavirin (RIB) and to new antiviral drugs. The prevalence of these mutations was examined in 69 drug-naive individuals with hepatitis C virus (HCV) infections in Rio de Janeiro, Brazil. Mutations related to non-response to IFN/RIB were observed in all subtypes studied (1a, 1b, 2b, 3a and 4). The most common mutation was Q309R, present in all subtypes, except subtype 2b with frequency above 20%. D244N was detected only in subtype 3a and A333E was detected only in subtype 2b. We did not detect the S282T, S326G or T329I mutations in any of the samples analysed. Of note, the C316N mutation, previously related to a new non-nucleoside compound (HCV796 and AG-021541), was observed in only eight of 33 (24%) samples from subtype 1b. Site 316 was under positive selection in this HCV variant. Our data highlight the presence of previously described resistance mutations in HCV genotypes from drug-naive patients.

CONTEXTUALIZAÇÃO: Os estudos sobre a relação entre prática de exercícios e bem-estar psicológico de pacientes com vírus da imunodeficiência humana (HIV) são raros. OBJETIVO: Investigar a influência de programa de condicionamento físico sobre a satisfação com a própria vida e sobre a função imunológica. MÉTODOS: Para tal análise, 29 pacientes soropositivos (idade: 45±2 anos; índice de massa corporal (IMC): 22,8±1,0 kg/m2; TCD4: 20,5±2,0%), foram divididos em grupo controle (GC, n=10) e grupo experimental (GE, n=19). O GE participou durante 12 semanas de programa de exercícios que combinavam exercícios aeróbios, força e flexibilidade (três vezes/semana; aeróbio-30min: carga em watts equivalente a 150bpm-PWC150; força-50min: três séries de 12 repetições em cinco exercícios a 60-80% 12 RM; flexibilidade-10min: duas séries de 30s na máxima amplitude em oito exercícios). A função imunológica foi avaliada por contagem absoluta e relativa das células TCD4 (citometria de fluxo),e a satisfação de vida, por meio do Índice de Satisfação de Vida (ISV). RESULTADOS: A análise de variância (ANOVA) não identificou alteração significativa para os linfócitos TCD4 em ambos os grupos, apesar da tendência à elevação no GE (16%, p=0,19). Houve melhora significativa no ISV (≈15%, P

To the Editor: Dengue viruses (DENVs) belong to the genus Flavivirus (family Flaviviridae) and exist as 4 antigenic types, serotypes 1–4, each with well-defined genotypes. Dengue virus is associated with clinical manifestations that range from asymptomatic infections and relatively mild disease (classic dengue fever) to more severe forms of dengue hemorrhagic fever and dengue shock syndrome. Dengue has become one of the most serious vector-borne diseases in humans. The World Health Organization estimates that 2.5 billion persons live in dengue-endemic areas and >50 million are infected annually (1). In 1986, dengue virus type 1 (DENV-1) caused an outbreak in the state of Rio de Janeiro and has since become a public health concern and threat in Brazil. (2). In 1990, DENV-2 was reported in the state of Rio de Janeiro, where the first severe forms of dengue hemorrhagic fever and fatal cases of dengue shock syndrome were documented. The disease gradually spread to other regions of the country (3). In 2002, DENV-3 caused the most severe dengue outbreak in the country and sporadic outbreaks continued to be documented through 2005 (4). Since 1990, two additional epidemics caused by DENV-2 have occurred (1998 and 2007–2008) in Brazil. A severe DENV-2 epidemic in the state of Rio de Janeiro began in 2007 and continued in 2008; a total of 255,818 cases and 252 deaths were reported (5). This epidemic prompted us to investigate the genetic relatedness of DENV-2 for all of these epidemics. DENV-2 isolates from these epidemic periods were subjected to sequencing and comparison. Gross sequences of DENV-2 isolates from all epidemic periods grouped with sequences from DENV-2 American/Asian genotype; this finding was expected because this genotype is circulating in the Americas (6,7). Sequences of DENV-2 isolates from the 1998 epidemic grouped with sequences of DENV-2 isolates from the 1990 epidemic (data not shown) suggesting that viruses circulating during these 2 epidemic periods belong to the same lineage of the DENV-2 strain originally found in the state of Rio de Janeiro. However, sequences of DENV-2 isolates from 2007/2008 epidemics grouped separately and distinctly from the 1990 and 1998 DENV-2 isolates and represented a monophyletic group in the phylogenetic tree with bootstraps of 98% (Figure). This result shows a temporal circulation of genetically different viruses in Rio de Janeiro that could be a result of local evolution of DENV-2 since its introduction in 1990, or even an introduction of a new lineage of DENV-2 in the region. Figure Neighbor-joining phylogenetic tree of 68 complete envelope (E) gene sequences of dengue virus type 2 (DENV-2). Only bootstrap values >80% are shown. DENV-2 sequences obtained from 21 patients infected during the 1990, 1998, and 2007–2008 ... A study conducted by Aquino et al. (7) showed that Paraguayan DENV-2 strains could be grouped as 2 distinct variants within the American/Asian genotype, thus further supporting that the introduction of new DENV-2 variants may likely associate with the shift of dominant serotypes from DENV-3 to DENV-2 in 2005 and might have caused an outbreak of DENV-2. Our results are consistent with this scenario because was a shift of a dominant serotype from DENV-3 to DENV-2 that was observed in 2008 in Rio de Janeiro. However, other factors, such as immunity level to DENV-3 and DENV-2, could explain the shift of dominant serotype besides the circulation of a new viral variant. Because the dengue outbreaks of 2007 and 2008 were the most severe of the dengue infections in Brazil in terms of number of cases and deaths, this genetically distinct DENV-2 could have contributed to this pathogenic profile. Additionally, these samples came from disperse locations in Rio de Janeiro and we do not believe that there is a clustering issue in our sampling. However, again, other factors must be considered as contributors to this scenario because of the intrinsic properties of this distinct virus, host susceptibility, and secondary cases of infection. In addition, detailed examination of amino acid sequences of Brazilian DENV-2 strains isolated in 1998 and 2008 showed 6 aa substitutions in the envelope gene: V129I, L131Q, I170T, E203D, M340T, and I380V. Our results support the notion that aa positions at 129 and 131 in the envelope gene are critical genetic markers for phylogenetic classification of DENV-2 (7–9). Notably, residue 131 in the envelope gene is located within a pH-dependent hinge region at the interface between domains I and II of the envelope protein. Mutations at this region may affect the pH threshold of fusion and the process of conformational changes (10). Our results suggest the circulation of genetically different DENV-2 in Brazil and that these viruses may have a role in severity of dengue diseases. These findings can help to further understand the complex dynamic pathogenic profile of dengue viruses and their circulation in dengue-endemic regions.

Twenty-one vertically HIV-1 infected children were assessed for drug resistance genotyping. Eighteen children presented at least one mutation conferring resistance to the nucleoside reverse transcriptase inhibitors, and seven children presented resistance to the non-nucleoside inhibitors. Among them, two children in whom the therapy had been discontinued two to three years before testing presented K101E, K103N, and G190A mutations conferring resistance to all the non-nucleoside drugs available for treatment. Protease gene mutations conferring resistance to at least two to up to twelve drugs were reported in 12 children. Studies in HIV-infected children have a particular meaning, and with antiretroviral therapy becoming more widely available, surveillance of viral resistance regional levels is relevant for treatment guidelines, supporting the rational use of antiretroviral drugs by treatment programs. Additional larger studies are still required to give more information on HIV-1 drug resistance in pediatric patients. DOI: http://dx.doi.org/10.17525/vrr.v14i2.29

Studies related to Human Immunodeficiency Virus type 1-infected children are of a special meaning due to multiple covariates such as timing of transmission, viral phenotypes, immunological patterns, viral dynamics progression and clinical evolution of disease. With antiretroviral therapy becoming more widely available, HIV resistance identification and monitoring of disease remains of great importance in infected children. The major HIV-1 infection markers usually used for monitoring viral infection and disease course are CD4+ T cell counts or percentages and HIV viral load. Both of them are helpful indicating when to start therapy and evaluating its efficacy. Also, their association with genotyping tests identifying viral resistant mutations may help clinicians for the most adequate clinical conduct. In the present study, we assessed HIV-1 viral load and CD4+ and CD8+ T lymphocyte rates for the immunological status evaluation of 25 antiretroviral-treated children or at the beginning of therapy, managing therapeutic regimens according to genotyping results. The management of highly active antiretroviral therapy (HAART) according to viral resistance in our group of pediatric patients allowed an increase in CD4+ T cell counts and/or percentage in almost all children, showing an improvement in their HIV-associated immunodeficiency status. Important viral burden declines were observed in 24 children, most of them multi-drug resistant, with HIV RNA undetectable levels reached in 12 of them. In particular, HAART introduction allowed a more significant viral load reduction for those pediatric patients who were drug treatment-naive, initiating antiretroviral therapy as they were enrolled at this study. DOI: http://dx.doi.org/10.17525/vrr.v14i1.23

The objectives of this study were to determine both the prevalence of microsporidial intestinal infection and the clinical outcome of the disease in a cohort of 40 HIV-infected patients presenting with chronic diarrhea in Rio de Janeiro, Brazil. Each patient, after clinical evaluation, had stools and intestinal fragments examined for viral, bacterial and parasitic pathogens. Microsporidia were found in 11 patients (27.5%) either in stools or in duodenal or ileal biopsies. Microsporidial spores were found more frequently in stools than in biopsy fragments. Samples examined using transmission electron microscopy (n=3) or polymerase chain reaction (n=6) confirmed Enterocytozoon bieneusi as the causative agent. Microsporidia were the only potential enteric pathogens found in 5 of the 11 patients. Other pathogens were also detected in the intestinal tract of 21 patients, but diarrhea remained unexplained in 8. We concluded that microsporidial infection is frequently found in HIV infected persons in Rio de Janeiro, and it seems to be a marker of advanced stage of AIDS.

Enterocytozoon bieneusi is the most prevalent microsporidian parasite that causes gastrointestinal infection in persons with AIDS. Microsporidia are increasingly recognized as important opportunistic pathogens all over the world but in Brazil only few cases have been reported due either to the non awareness of the clinical presentation of the disease or to difficulties in the laboratory diagnosis. We report a 3-year follow-up of a Brazilian HIV-positive patient in whom microsporidial spores were detected in stools and were identified as E. bieneusi using electron microscopy and PCR. The patient presented with chronic diarrhea, CD4 T-lymphocytes count below 100/mm3 and microsporidial spores were consistently detected in stools. Albendazole was given to the patient in several occasions with transient relief of the diarrhea, which reappeared as soon as the drug was discontinued. Nevertheless, a diarrhea-free period with weight gain up to 18 Kg occurred when a combination of nucleoside and protease inhibitors was initiated as part of the antiviral treatment.Enterocytozoon bieneusi é o mais comum microsporídio agente de infecções gastrointestinais que ocorre predominantemente em pessoas com AIDS. Em todo o mundo os microsporídios são reconhecidos como importantes patógenos oportunistas, entretanto poucos casos já foram diagnosticados no Brasil, provavelmente devido ao pouco conhecimento do quadro clínico que os agentes produzem ou a dificuldades no diagnóstico laboratorial. No presente trabalho relatamos o caso de um paciente brasileiro HIV-positivo acompanhado durante 3 anos, em que foram detectados esporos de microsporídios nas fezes, identificados como Enterocytozoon bieneusi por microscopia eletrônica e PCR. O paciente apresentava diarréia crônica, contagem de linfócitos CD4 abaixo de 100/mm3 e fez uso de albendazol em diferentes ocasiões com melhora transitória da diarréia, que reaparecia logo que a droga era suspensa. Entretanto, o paciente apresentou um grande período sem diarréia e com ganho ponderal de até 18 Kg quando foi prescrito como terapêutica antiretroviral uma combinação de nucleosídios e inibidores de protease.

The occurrence of intestinal parasites, its relation with the transmission mechanism of HIV, and the clinical state of the AIDS patients, were analyzed in 99 Group IV patients (CDC, 1986), treated at "Hospital Universitário Pedro Ernesto" (HUPE), between 1986 and 1988. The group consisted of 79 (79.8%) patients whose HIV transmission mechanism took place through sexual contact and of 16 (20.2%) who were infected through blood. Feces samples from each patient were examined by four distincts methods (Faust et al, Kato-Katz, Baermann-Moraes and Baxby et al.). The moste occuring parasites were: Cryptosporidium sp., Entamoeba coli and Endolimax nana (18.2%), Strongyloides stercoralis and Giardia lambia (15.2%). E. histolytica and/or E. hartmanni (13.1%), Ascaris lumbricoides (11.1%) and Isospora belli (10.1%). Furthermore, 74.7% of the patients carried at least one species. Intestinal parasites were found in 78.5% of the patients who acquired the HIV through sexual intercourse and in 56,3% of those infected by blood contamination. The difference, was not statistically significant (p > 0.05). In the group under study, the increase of the occurrence of parasitc infections does not seem to depend on the acquisiton of HIV through sexual contact. It appears that in developing countries, the dependancy is more related to the classic mechanisms of parasites transmission and its endemicity. A ocorrência de parasitas intestinais, sua relação com o mecanismo de transmissão do HIV e a apresentação clínica da AIDS foram analisadas em 99 pacientes do grupo IV (CDC, 1986), atendidos no Hospital Universitário Pedro Ernesto (HUPE) entre 1986 e 1988. O grupo era constituído de 79 (79,9%) pacientes cujo mecanismos de transmssão do HIV se deu por via sexual e de 16 (20,2%) que se infectaram por via sanguínea. Amostras de fezes de cada paciente foram examinadas por quatro métodos distintos (Faust et al., Kato-Katz, Baermann-Moraes e Baxby et al.). Os parasitos mais frqüentemente encontrados foram: Cryptosporidium sp., Entamoeba coli e Endolimax nana (18,2%) seguidos de Strongyloides stercoralis e Giardia lamblia (15,2%), E. histolytica e/ou E. hartmanni (13,1%), Ascaris lumbricoides (11,1%) e Isospora belii (10,1%), sendo que 74,4% dos pacientes com AIDS albergavam pelo menos uma espécie. Observamos que 78,5% dos pacientes que adquiriram o HIV por via sexual e 56,3% dos que foram infectados por via sanguínea albergavam parasitos intestinais, mas a diferença não foi estatisticamente significativa (p>0,05). O mecanisto de infecção por via sexual não parece contribuir de forma importante para o aumento da ocorrência de infecções parasitárias no grupo estudado e sim os mecanismos clássicos de transmissão de parasitos em nosso meio.