Epidemiological profile of HIV older adults who are patients in a reference center in Aracaju-SE / Perfil epidemiológico dos pacientes idosos com HIV em um centro de referência de Aracaju-SE / Perfil epidemiológico de pacientes ancianos con VIH en un centro de referencia en Aracaju-SE

Background and objectives: Acquired Immunodeficiency Syndrome (AIDS) is a disease caused by HIV. 3% of the people living with HIV/AIDS in Brazil are 60 years old or over. Although older adults correspond to a small percentage, there has been a significant increase in the incidence in this group in recent years. Thus, HIV infection in older adults is a reality, however, literature hardly addresses this topic. The objective is to study the epidemiological clinical profile of older adults living with HIV monitored at a referral center. Methods:This is an observational, descriptive, cross-sectional study with data collection obtained from the medical records of the STI/AIDS outpatient clinic at a reference center. The data were sociodemographic, clinical and laboratory, collected from September 2018 to February 2019. Results:In the reference center, 309 older adults were registered, representing 6.7% of all patients registered in the service. Of these, 75.6% are men, 38% are married, 70% heterosexual and approximately 50% with low education. Comorbidities are associated, with dyslipidemia (54%) being the main one. At the time of diagnosis, 65.8% had detectable viral load and 62% had CD4 + cells <500 cls/mm³ and after therapeutic follow-up, only 20% had detectable viral load. Several therapeutic regimens are used, the main one being Tenofovir, Lamivudine and Efavirenz (35.3%). Conclusion: The epidemiological profile of the population served in the region follows national and global characteristics, with a predominance of men, heterosexuals, married and with low education.(AU)

Justificativa e Objetivos: A Síndrome da Imunodeficiência Adquirida (SIDA) é uma doença causada pelo HIV. Das pessoas vivendo com HIV(PVHIV)no Brasil, 3% apresentam 60 anos ou mais. Apesar dos idosos corresponderem a um pequeno percentual, há aumento significativo da incidência nesse grupo nos últimos anos. Dessa forma, a infecção pelo HIV em idosos é uma realidade, contudo, a literatura pouco aborda esse tema. O objetivo do trabalho é estudar o perfil clínico epidemiológico dos idosos vivendo com HIV acompanhados em um centro de referência. Métodos: Trata-se de um estudo observacional, descritivo, de corte transversal, com coleta de dados obtida através dos prontuários do ambulatório de IST/SIDA de um centro de referência. Os dados sociodemográficos, clínicos e laboratoriais, foram coletados no período setembro de 2018 a fevereiro de 2019. Resultados: No centro de referência, estão cadastrados 309 idosos, representando 6,7% de todos os pacientes matriculados no serviço. Destes, 75,6% são homens, 38% casados, 70% de orientação heterossexual e aproximadamente 50% com baixa escolaridade. Comorbidades estão associadas, sendo a dislipidemia (54%) a principal. No momento do diagnóstico, 65,8% apresentavam carga viral (CV) detectável,62% tinham células CD4+ < 500céls/mm³ e após seguimento terapêutico apenas 20% apresentavam CV detectável. Vários esquemas terapêuticos foram utilizados, sendo o principal Tenofovir, Lamivudina e Efavirenz (35,3%). Conclusão: O perfil epidemiológico da população atendida na região segue as características nacionais e mundiais, com predomínio de homens, heterossexuais, casados e de baixa escolaridade.(AU)

Justificación y Objetivos: El Síndrome de Inmunodeficiencia Adquirido(SIDA) es una enfermedad causada por el VIH. De las personas que viven con el VIH (PVVIH) en Brasil, el 3% tiene 60 años o más. Aunque los adultos mayor es corresponden a un pequeño porcentaje, en los últimos años se ha producido un aumento significativo de la incidencia en este grupo. La infección por VIH en los adultos mayores es una realidad; sin embargo, la literatura aborda poco este tema. El objetivo de este trabajo es estudiar el perfil clínico epidemiológico de adultos mayores que conviven con el VIH y se atienden en un centro de referencia. Métodos: Se trata de un estudio observacional, descriptivo, de corte transversal, con datos obtenidos de los registros de ETS/SIDA de un centro de referencia. Se recogieron datos sociodemográficos, clínicos y de laboratorio desde septiembre de 2018 hasta febrero de 2019. Resultados: En el centro de referencia están registrados309 adultos mayores, que representan el 6,7% de todos los pacientes inscriptos en el servicio. De ellos, el 75,6% es del sexo masculino, el 38%, casado, el 70% con orientación heterosexual y aproximadamente el 50% con baja escolaridad. De las comorbilidades asociadas, la dislipidemia esla principal (54%). En el momento del diagnóstico, el 65,8% tenía una carga viral detectable (CV), el 62%tenía células CD4+<500 células/mm³ y después del seguimiento terapéutico sólo el 20% tenía CV detectable. Se utilizaron varios esquemas terapéuticos, siendo los principales el Tenofovir, la Lamivudina y el Efavirenz (35,3%). Conclusión: El perfil epidemiológico de la población atendida en la región sigue las características nacionales e internacionales, con predominio de hombres heterosexuales, casados y de baja escolaridad.(AU)

Neurochagas: atualização clínica / Neurochagas: clinical update

A doença de Chagas ainda é uma doença tropical muito prevalente no Brasil. Pode apresentar duas fases (aguda e crônica) e exibe grandes repercussões, sobretudo as que envolvem o sistema nervoso periférico e/ou central. Com o aumento do número de pessoas vivendo em estado (transitório ou permanente) de imunossupressão, os casos de manifestações neurológicas por neurochagas aumentaram, e este tornou-se um importante diagnóstico diferencial com outras doenças oportunistas. Este artigo teve como objetivo revisar os principais aspectos clínicos e terapêuticos da doença de Chagas no sistema nervoso central.

Chagas disease is still a very prevalent tropical disease in Brazil. It can have two phases - acute and chronic ­ and shows major repercussions, especially those involving the peripheral and/ or central nervous system. With the increase in the number of people living in the (transient or permanent) state of immunosuppression the cases of neurological manifestations of Chagas disease increased and this became an important differential diagnosis with other opportunistic diseases. This article aimed to review the main clinical and therapeutic aspects of central nervous system Chagas disease

Interleukin-6 and Interferon-α Levels in Gingival Crevicular Fluid in HIV-1 Patients with Chronic Periodontitis / Niveles de Interleukin-6 e Interferon-α de Fluido Crevicular Gingival en Pacientes VIH-1 con Periodontitis Crónica

ABSTRACT: The influence of cytokine on the progression of chronic periodontitis in human immunodeficiency virus (HIV) patients is still controversial and poorly investigated. This study aimed to analyze and compare IL-6 and IFN-α levels in the gingival crevicular fluid of HIV-1-positive and HIV-1-negative patients with chronic periodontitis and different grades of tissue destruction and inflammation. Samples from the gingival crevicular sulcus were obtained from 35 HIV-1-positive individuals with chronic periodontitis and 35 seronegative patients with chronic periodontitis. Probing depth and clinical attachment level, as well as the results of the Enzyme-Linked Immunosorbent Assay for confirmation of patient diagnostics, were evaluated. Statistical analyses were performed using Student t, Mann-Whitney and Spearman tests. IL-6 levels were significantly lower, while IFN-α levels were significantly higher in HIV-1 patients. Clinical attachment level was directly associated with IFN-α levels in HIV-1 carriers, connected to probing depth in these patients. Clinical data in association with gingival crevicular fluid cytokine levels may reveal a localized immunological response pattern, which may contribute to the understanding of periodontitis pathogenesis in HIV-1 carriers.

RESUMEN: La influencia de la citocina en la progresión de la periodontitis crónica en pacientes con el virus de la inmunodeficiencia humana (VIH) sigue siendo controvertida y poco investigada. Este estudio tuvo como objetivo analizar y comparar los niveles de interleuquina-6 (IL6) e interferón-α (IFN-α) en el líquido crevicular gingival de pacientes VIH-1-positivos y VIH-1-negativos con periodontitis crónica y diferentes grados de destrucción e inflamación tisular. Se obtuvieron muestras del surco crevicular gingival de 35 individuos VIH-1 positivos con periodontitis crónica y 35 pacientes seronegativos con periodontitis crónica. Se evaluaron la profundidad de sondeo y el nivel de inserción clínica, así como los resultados del Ensayo Inmunoabsorbente Ligado a Enzimas para la confirmación del diagnóstico del paciente. Los análisis estadísticos se realizaron utilizando pruebas t de Student, Mann-Whitney y Spearman. Los niveles de IL-6 fueron significativamente más bajos, mientras que los niveles de IFN-a fueron significativamente más altos en los pacientes con VIH-1. El nivel de inserción clínica se asoció directamente con los niveles de IFN-α en los portadores del VIH1, conectados a la profundidad del sondaje en estos pacientes. Los datos clínicos en asociación con los niveles de citoquinas de los fluidos creviculares gingivales pueden revelar un patrón de respuesta inmunológica localizado, que puede contribuir a la comprensión de la patogénesis de la periodontitis en los portadores del VIH-1.

Social conditions and immune response in human immunodeficiency virus-seropositive pregnant women: a cross-sectional study in Brazil

Abstract INTRODUCTION The functioning of the immune system during pregnancy is altered in both human immunodeficiency virus (HIV)-infected and uninfected women. Unfavorable socioeconomic conditions have been indicative of higher morbidity and mortality and worsening of the immune system. The aim of this study was to correlate social status with levels of interleukin (IL)-10 (non-inflammatory) and interferon-gamma (IFN-γ; inflammatory) cytokines. METHODS A cross-sectional study was conducted with three groups of women: 33 pregnant HIV-infected (G1); 40 non-pregnant, HIV-infected (G2); and 35 pregnant, HIV-uninfected. To measure the social status, a compound indicator called the social status index (SSI), was established using sociodemographic variables (i.e., education level, housing conditions, per capita income, and habitation and sanitary conditions). RESULTS The HIV-infected women had a higher proportion of unfavorable SSI (73% and 75% of G1 and G2, respectively). There were significantly lower IL-10 levels in the G1 group with both unfavorable and favorable SSI than in the other groups. No significant difference in IFN-γ levels was observed among groups. However, the G1 group had higher IFN-γ values among both favorable and unfavorable SSI groups. CONCLUSIONS Higher rates of unfavorable conditions, including lower education levels, IL-10 levels, and a trend for higher IFN-γ levels, were identified among HIV-infected women, pregnant and non-pregnant. These factors may interfere in health care and lead to poor outcomes during pregnancy. Therefore, we suggest that health policies could be created to specifically address these factors in this population.

Role of T. cruzi exposure in the pattern of T cell cytokines among chronically infected HIV and Chagas disease patients

OBJECTIVES: The impact of Chagas disease (CD) in HIV-infected patients is relevant throughout the world. In fact, the characterization of the adaptive immune response in the context of co-infection is important for predicting the need for interventions in areas in which HIV and Chagas disease co-exist. METHODS: We described and compared the frequency of cytokine-producing T cells stimulated with soluble antigen of Trypanosoma cruzi (T. cruzi) using a cytometric assay for the following groups: individuals with chronic Chagas disease (CHR, n=10), those with Chagas disease and HIV infection (CO, n=11), those with only HIV (HIV, n=14) and healthy individuals (C, n=15). RESULTS: We found 1) a constitutively lower frequency of IL-2+ and IFN-γ+ T cells in the CHR group compared with the HIV, CO and healthy groups; 2) a suppressive activity of soluble T. cruzi antigen, which down-regulated IL-2+CD4+ and IFN-γ+CD4+ phenotypes, notably in the healthy group; 3) a down-regulation of inflammatory cytokines on CD8+ T cells in the indeterminate form of Chagas disease; and 4) a significant increase in IL-10+CD8+ cells distinguishing the indeterminate form from the cardiac/digestive form of Chagas disease, even in the presence of HIV infection. CONCLUSIONS: Taken together, our data suggest the presence of an immunoregulatory response in chronic Chagas disease, which seems to be driven by T. cruzi antigens. Our findings provide new insights into immunotherapeutic strategies for people living with HIV/AIDS and Chagas disease.

The absence of the human platelet antigen polymorphism effect on fibrosis progression in human immunodeficiency virus-1/hepatitis C virus coinfected patients

Hepatic fibrosis progression in patients with chronic hepatitis C virus infections has been associated with viral and host factors, including genetic polymorphisms. Human platelet antigen polymorphisms are associated with the rapid development of fibrosis in HCV-monoinfected patients. This study aimed to determine whether such an association exists in human immunodeficiency virus-1/hepatitis C virus-coinfected patients.

Social and immunological differences among uninfected Brazilians exposed or unexposed to human immunodeficiency virus-infected partners

Understanding the social conditions and immunological characteristics that allow some human immunodeficiency virus (HIV)-exposed patients to remain uninfected represents an on-going challenge. In this study, the socio-demographic and sexual behaviour characteristics and immune activation profiles of uninfected individuals exposed to HIV-infected partners were investigated. A confidential and detailed questionnaire was administered and venous blood was tested using HIV-1/enzyme immunoassays, plasma HIV-1 RNA levels/bDNA and immunophenotyping/flow cytometry to determine the frequencies of CD4 and CD8 T cells expressing activation markers. The data analysis showed significant differences (p < 0.05) for immune parameters in individuals who were uninfected, albeit exposed to HIV-infected partners, compared with unexposed individuals. In particular, the exposed, uninfected individuals had a higher frequency (median, minimum-maximum) of CD4+HLA-DR+ (4.2, 1.8-6.1), CD8+HLA-DR+ (4.6, 0.9-13.7), CD4+CD45RO+ (27.5, 14.2-46.6), CD4+CD45RO+CD62L+ (46.7, 33.9-67.1), CD8+CD45RA+HLA-DR+ (12.1, 3.4-35.8) and CD8+CD45RO+HLA-DR+ (9.0, 3.2-14.8) cells, a decreased percentage of CD8+CD28+ cells (11.7, 4.5-24.0) and a lower cell-surface expression of Fcγ-R/CD16 on monocytes (56.5, 22.0-130.0). The plasma HIV-1 RNA levels demonstrated detectable RNA virus loads in 57% of the HIV-1+ female partners. These findings demonstrate an activation profile in both CD4 and CD8 peripheral T cells from HIV-1 exposed seronegative individuals of serodiscordant couples from a referral centre in Belo Horizonte, state of Minas Gerais.

Factors associated with a diagnosis of major depression among HIV-infected elderly patients

Introduction Acquired immunodeficiency syndrome (AIDS) is being increasingly reported among the elderly and major depression (MD) may be associated with suboptimal adherence to treatment. Methods Cross-sectional study on factors associated with MD among 72 HIV-infected elderly individuals. Results Twenty (27.7%) patients were found to have MD. The female gender (odds ratio [OR] = 10.65; p = 0.00586), a low CD4 count during the study (OR = 1.005247; p = 0.01539), and current smoking status (OR = 12.89; p = 0.01693) were independently associated with MD. Conclusions Our data underscore the need to attentively search and treat MD among HIV-infected elderly patients. .

A comparative analysis of outpatient costs in HIV treatment programs / Análise comparativa dos custos ambulatoriais em programas de tratamento de pacientes HIV

OBJECTIVE: To analyze the costs of human immunodeficiency virus (HIV) outpatient treatment for individuals with different CD4 cell counts in the Brazilian public health system, and to compare to costs in other national health systems. METHODS: A retrospective survey was conducted in five public outpatient clinics of the Brazilian national HIV program in the city of São Paulo. Data on healthcare services provided for a period of one year of HIV outpatient treatment were gathered from randomly selected medical records. Prices of inputs used were obtained through market research and public sector databases. Information on costs of HIV outpatient treatment in other national health systems were gathered from the literature. Annual costs of HIV outpatient treatment from each country were converted into 2010 U.S. dollars. RESULTS: Annual cost of HIV outpatient treatment for the Brazilian national public program was US$ 2,572.92 in 2006 in São Paulo, ranging from US$ 1,726.19 for patients with CD4 cell count > 500 to US$ 3,693.28 for patients with 51 < CD4 cell count < 200. Antiretrovirals (ARVs) represented approximately 62.0% of annual HIV outpatient costs. Comparing among different health systems during the same period, HIV outpatient treatment presented higher costs in countries where HIV treatment is provided by the private sector. CONCLUSION: The main cost drivers of HIV outpatient treatment in different health systems were: ARVs, other medications, health professional services, and diagnostic exams. Nevertheless, the magnitude of cost drivers varied among HIV outpatient treatment programs due to health system efficiency. The data presented may be a valuable tool for public policy evaluation of HIV treatment programs worldwide.

OBJETIVO: Analisar custos de tratamento ambulatorial de pacientes portadores do vírus da imunodeficiência humana (HIV) com diferentes níveis de CD4 no sistema público de saúde brasileiro e comparar aos custos de outros sistemas de saúde. MÉTODOS: Foi conduzida pesquisa retrospectiva em cinco ambulatórios especializados do programa DST/AIDS no município de São Paulo. Dados referentes à assistência ambulatorial para tratamento de pacientes HIV durante um ano foram obtidos em prontuários médicos selecionados aleatoriamente. Preços dos recursos utilizados foram obtidos via pesquisa de mercado e bancos de dados do setor público. Informações sobre custos do tratamento ambulatorial de pacientes HIV em outros sistemas de saúde foram obtidos na literatura. Os custos anuais de tratamento ambulatorial de pacientes HIV em cada país foram convertidos em dólares norte-americanos no ano base 2010. RESULTADOS: O custo anual de tratamento ambulatorial para pacientes HIV no programa público nacional foi US$ 2.572,92 em 2006 no município de São Paulo, variando entre US$ 1.726,19 para pacientes com CD4 > 500 e US$ 3.693,28 para pacientes com 51 < CD4 < 200. Medicamentos antirretrovirais (ARVs) representaram aproximadamente 62,0% dos custos de tratamento ambulatorial de pacientes HIV. Comparando-se custos entre diferentes sistemas de saúde no mesmo período, o tratamento ambulatorial de pacientes HIV apresentou custos superiores nos países onde a provisão do tratamento é realizada pelo setor privado. CONCLUSÃO: Os principais determinantes dos custos de tratamento ambulatorial de pacientes HIV são: medicamentos ARVs, outros medicamentos, profissionais de saúde e exames diagnósticos. No entanto, a magnitude de participação dos determinantes de custos nos programas de tratamento ambulatorial de pacientes HIV varia em decorrência da eficiência do sistema de saúde. Os dados apresentados constituem importante instrumento para avaliação de políticas públicas de saúde relacionadas ao tratamento de pacientes HIV mundialmente.

Eliminating vertically-transmitted HIV/AIDS while improving access to treatment and care for women, children and adolescents in Jamaica / Eliminando la transmisión vertical del VIH/SIDA mejorando a la par el acceso al tratamiento y el cuidado de las mujeres, los niños y los adolescentes en Jamaica

BACKGROUND AND METHODS: To celebrate Jamaica's 50th birthday after receiving independence from Great Britain, we summarize our collaborative published research in the prevention, treatment and care of paediatric, perinatal and adolescent HIV/AIDS in Jamaica. RESULTS: Public access to antiretroviral therapy (ART) in Jamaica has shown that a "test and treat" strategy associated with "treatment for prevention" works for HIV-infected pregnant women by reducing their HIV-attributable morbidity and mortality and reducing mother-to-child transmission (MTCT) rates to < 2%, islandwide. These women experience significant psychosocial stress and targeted interventions are assisting them to improve their quality of life. HIV-exposed and infected children come from large families with high rates of teen pregnancies and significant financial challenges needing sustained interventions. HIV-exposed but uninfected Jamaican infants have higher rates of community-acquired infections, including lower respiratory tract infections, sepsis and gastroenteritis compared to community controls, although their growth rates are normal. In evaluation of replication capacity, viral control and clinical outcomes after vertical transmission in Jamaican mother-infant pairs, HLA-B57 was found to confer the advantage of restricted HIV replication primarily by driving and maintaining a fitness-attenuating mutation in p-24 Gag. Viral sequences from 52 MTCT Jamaican pairs were compared and 1475 sites of mother-infant amino acid divergence within Nef, Gag and Pol were identified, suggesting modest fitness cost with many CD8 mutations. HIV-infected Jamaican children are surviving into adolescence and adulthood, as a result of increased public access to ART and improved collaborative capacity in ART management. Successful transition of HIV-infected children through adolescence into adulthood requires a strong multidisciplinary team approach, including long-term ART management addressing non-adherence, drug resistance and toxicity, treatment failure and limited options for second line and salvage therapy, while attending to their sexual and reproductive health, psychosocial, educational and vocational issues and palliative care. CONCLUSION: Over the past nine years, Jamaica has made excellent strides to eliminate vertically transmitted HIV/AIDS, while reducing the HIV-attributable morbidity and mortality in pregnant women and in HIV-infected children. Continued successful transition of HIV-infected children through adolescence into adulthood will require a strong multidisciplinary team approach.

ANTECEDENTES Y MÉTODOS: A fin de celebrar el 50 aniversario de Jamaica tras recibir la independencia de Gran Bretaña, resumimos nuestra investigación colaborativa publicada sobre la prevención, tratamiento y cuidado del VIH/SIDA pediátrico, perinatal y juvenil en Jamaica. RESULTADOS: El acceso público a la terapia antiretroviral (TAR) en Jamaica ha mostrado que una estrategia "test and treat" asociada con el "tratamiento para la prevención" funciona de manera efectiva con mujeres embarazadas infectadas por VIH, reduciendo la morbilidad y la mortalidad atribuibles al VIH, y disminuyendo las tasas de transmisión madre a niño (MTCT) a < 2% en toda la isla. Estas mujeres experimentan un estrés psicosocial considerable, y las intervenciones aplicadas están ayudándolas a mejorar su calidad de vida. Los niños expuestos e infectados por el VIH provienen de familias numerosas con altas tasas de embarazos adolescentes y considerables retos financieros. Se trata pues de familias que necesitan intervenciones sostenidas. Los infantes jamaicanos expuestos pero no infectados por el VIH tienen tasas más altas de infecciones adquiridas en la comunidad - incluyendo infecciones de las vías respiratorias bajas, sepsis y gastroenteritis - en comparación con los controles comunitarios, si bien sus tasas de crecimiento eran normales. Al evaluar la capacidad de replicación, el control viral, y los resultados clínicos tras la transmisión vertical en pares madre-infante jamaicanos, se halló que el HLA-B57 confería la ventaja de restringir la replicación del VIH mediante la conducción y mantenimiento de una mutación atenuante de la aptitud adaptativa (fitness) en p-24 gag. Las secuencias virales de 52 pares jamaicanos MTCT fueron comparadas, y se identificaron 1475 sitios de divergencia de aminoácido de madre-infante dentro de nef, gag y pol, lo cual sugiere un costo modesto de aptitud adaptativa con muchas mutaciones de CD8. Los niños jamaicanos infectados por VIH están sobreviviendo hasta llegar a ser adolescentes o adultos, como resultado del aumento del acceso público a la TAR, y al mejoramiento de capacidad colaborativa en el tratamiento de TAR. La transición exitosa de niños infectados con VIH a través de la adolescencia hasta la adultez requiere un enfoque multidisciplinarlo en equipo, incluyendo el tratamiento de TAR a largo plazo. Dicho tratamiento se dirige a la no adherencia, la resistencia a los medicamentos y la toxicidad, el fracaso del tratamiento y opciones limitadas para las terapias de segunda línea y de salvamento, a la par que se atiende a la salud reproductiva y sexual de los pacientes, a los problemas vocacionales, educacionales y psicosociales, y el cuidado paliativo. CONCLUSIÓN: En los últimos nueve años, Jamaica ha dado pasos extraordinarios para eliminar la transmisión vertical del VIH/SIDA, reduciendo la morbilidad y la mortalidad atribuibles al VIH en mujeres embarazadas y en niños infectados por VIH. La transición exitosa continuada de los niños infectados por VIH a través de la adolescencia hasta la adultez requerirá un fuerte enfoque multidisciplinarlo en equipo.

A Imunologia da infecção pelo HIV em pacientes com idade avançada: caracterização fenotípica e funcional da resposta imune mediada pela célula T CD4+ / Immunology of HIV infection in patients with advanced age: phenotypic and functional immune response mediated by CD4+ cell

A proporção de idosos portadores da síndrome da imunodeficiência adquirida (aids) tem aumentado de maneira importante nos últimos anos e, até a presente data, existem poucos estudos que abordam a infecção nessa população especial. As particularidades imunológicas decorrentes do fenômeno da imunossenescência podem acarretar mudanças significativas na evolução da infecção pelo HIV, bem como na resposta ao tratamento. O objetivo maior desta Tese foi avaliar o impacto da idade na recuperação funcional do sistema imune de pacientes com aids acima de 55 anos, quando tratados adequadamente com terapia anti-retroviral, caracterizando a resultante imunológica da idade avançada e da infecção pelo HIV. Para tanto, foram estudados quatro grupos experimentais: indivíduos jovens saudáveis ou com aids, e indivíduos acima de 55 anos saudáveis ou com aids. Todos os pacientes com aids estavam recebendo terapia anti-retroviral, em sucesso terapêutico. No primeiro artigo apresentado, avaliamos resposta linfoproliferativa e produção de citocinas in vitro e resposta humoral in vivo mediante desafio antigênico com toxóide tetânico (TT) em indivíduos previamente vacinados contra o tétano. Os resultados mostraram deficiências imunológicas significativas relacionadas à idade avançada no que diz respeito a produção de IgG anti-TT, resposta linfoproliferativa e produção de IFN-y. Em contrapartida, a produção de IL-10 foi significativamente maior nos indivíduos acima de 55 anos, infectados ou não pelo HIV. No segundo artigo, foram caracterizadas as subpopulações de células T mediante estímulo policlonal ou específico com antígenos do envelope do HIV (Env). Em culturas não-estimuladas de PBMC do grupo com aids e idade avançada, observamos frequência reduzida de células T naive e de memória central, associada a aumento de células T efetoras. Quando estimuladas policlonalmente, essas culturas apresentaram deficiência na produção de IFN-y e hiperprodução de IL-10, como na resposta ao TT...

The proportion of aged persons living with the acquired immunodeficiency syndrome (aids) has importantly increased in recent years and, up to the present moment, there are few studies that address the infection in this particular population. The immunological nuances resulting from the immunosenescence phenomenon may promote significant alterations in the clinical course of HIV infection, as well as in treatment response. The major purpose of this Thesis was to evaluate the impact of age on the functional immune recovery in aids patients aged more than 55 years, when adequately treated with anti-retroviral therapy, characterizing the immunological result of advanced age and HIV infection. Thus, four experimental groups were enrolled: healthy or HIV-infected young adults, and healthy or HIV-infected adults over 55 years old. All the HIV-infected patients had diagnosis of aids and were under anti-retroviral treatment with therapeutic success. In the first presented article, we evaluated the lymphoproliferative response and cytokine production in vitro and humoral response in vivo, after antigenic challenge with tetanus toxoid (TT) in previously immunized individuals against tetanus. The results revealed significant age-related immunological impairments concerning anti-TT IgG production, lymphoproliferative response and production of IFN-y. On the other hand, the production of IL-10 significantly higher in individuals aged more the 55 years, HIV-infected or not. In the second article, T cell subsets were characterized after polyclonal activation or specific stimulus with antigens derived from the HIV envelope (Env). In fresh unstimulated PBMC cultures obtained from the aged aids patients, there was a reduced frequency of naïve and central memory T cells, associated with increased frequency of effector T cells. When polyclonally stimulated, these cultures showed deficient production of IFN-y and hyperproduction of IL-10, like in response to TT...

Fatores associados à evolução em múltiplos estados de saúde depacientes HIV soropositivos / Factors associated with changes in multiple health states depacientes HIV seropositive

Poucos estudos avaliam fatores associados a progressão entre estados m ultiplos de sa ude. Recentemente, modelos de sobrevivência multi-estado tem sido propostos para a avaliação deeventos m ultiplos, o que se torna util no contexto de doenças crônicas, como a infec ção pelo HIV. Diferentemente dos modelos de Cox, os modelos multi-estado permitem a estima ção de diferentes fatores associados a cada transi ção entre esses estados de sa ude. Esta tese pretende avaliar os fatores associados a cada mudan ca dos estados de sa ude na infeçãao pelo HIV, em duas diferentes estrat egias: pela avalia ção do estado imunol ogico e pela ocorrência de doen ças não-relacionadas diretamente a AIDS. A população de estudo consiste de pacientes infectados pelo HIV em pelo menos um per odo de uso de tratamento antirretroviral altamente potente (HAART), atendidos num centro de referência em doen cas infecciosas no Rio de Janeiro. No primeiro artigo, 722 pacientes atendidos entre 2006 e 2008 foram analisados quanto aos fatores associados, incluindo adesão ao antirretroviral, a mudan ca entre estados imune. O segundo artigo discute a teoria dos modelos multi-estado e descreve aplicação no software livre R, utilizando os mesmos 722 pacientes. O terceiro artigo investiga os diferentes fatores associados a cada mudan ca entre estados de gravidade, em 1135 pacientes atendidos entre 1996 e 2010, determinados por comorbidades relacionadas a ocorrência cardiovascular. (...) A importância dos modelos multi-estado e clara no contexto da progressão de doen ças crônicas e a discussão dessa abordagem tem por objetivo exemplicar sua aplica ção, seja na infec ção pelo HIV ou em outra doen ca crônica, permitindo a ado ção de diferentes estrat egiasde prevenção ao longo do acompanhamento, de acordo com o estado atual do paciente.

Co-infection Trypanosoma cruzi/HIV: systematic review (1980 - 2010) / Coinfecção Trypanosoma cruzi/HIV: revisão sistemática (1980 - 2010)

INTRODUCTION: The co-infection Trypanosoma cruzi/HIV has been described as a clinical event of great relevance. The objective of this study wasto describe clinical and epidemiological aspects published in literature. METHODS: It is a systematic review of a descriptive nature from the databases Medline, Lilacs, SciELO, Scopus, from 1980 to 2010. RESULTS: There were 83 articles (2.8 articles/year) with a total of 291 cases. The co-infection was described in 1980 and this situation has become the defining AIDS clinical event in Brazil. This is the country with the highest number of publication (51.8 percent) followed by Argentina (27.7 percent). The majority of cases are amongst adult men (65.3 percent) native or from endemic regions with serological diagnosis in the chronic stage (97.9 percent) and indeterminate form (50.8 percent). Both diseases follow the normal course, but in 41 percent the reactivation of the Chagas disease occurs. The most severe form is the meningoencephalitis, with 100 percent of mortality without specific and early treatment of the T. cruzi. The medication of choice was the benznidazole on doses and duration normally used for the acute phase. The high parasitemia detected by direct or indirect quantitative methods indicated reactivation and its elevation is the most important predictive factor. The lower survival rate was related to the reactivation of the Chagas disease and the natural complications of both diseases. The role of the antiretroviral treatment on the co-infection cannot yet be defined by the knowledge currently existent. CONCLUSIONS: Despite the relevance of this clinical event there are still gaps to be filled.

INTRODUÇÃO: A coinfecção Trypanosoma cruzi/HIV vem sendo sistematicamente descrita como um evento clínico de grande relevância. O objetivo deste estudo foi descrever aspectos clínicos e epidemiológicos publicados na literatura científica. MÉTODOS: Trata-se de revisão sistemática, de natureza descritiva, a partir da busca nas bases Medline, Lilacs, SciELO, Scopus, de 1980 a 2010. RESULTADOS: Identificou-se 83 artigos (2,8 artigos/ano), com um total de 291 casos registrados. A coinfecção foi descrita em 1980 e, no Brasil, tornou-se evento clínico definidor de AIDS. Este é o país com maior número de publicações (51,8 por cento), seguido pela Argentina (27,7 por cento). A maioria dos casos é de homens adultos (65,3 por cento), naturais ou procedentes de regiões endêmicas, com diagnóstico sorológico, na fase crônica (97,9 por cento) e na forma indeterminada (50,8 por cento). As duas doenças evoluem naturalmente, mas em 41 por cento dos casos ocorreu reativação da doença de Chagas. A forma mais grave é a meningoencefalite, com 100 por cento de letalidade nos casos sem tratamento específico e precoce do T. cruzi. O medicamento indicado foi benznidazole, nas doses e duração utilizadas na fase aguda em imunocompetentes. O diagnóstico da reativação foi comprovado por alta parasitemia, detectada por métodos diretos ou indiretos quantitativos, sendo a sua elevação considerada fator preditivo para reativação. A menor sobrevida nacoinfecção esteve relacionada à reativação da doença de Chagas e às complicações naturais de ambas as doenças. O papel do tratamento antirretroviral sobre a evolução da coinfecção ainda não pode ser definido pelo conhecimento existente. CONCLUSÕES: Apesar da relevância deste evento clínico, ainda persistem lacunas a serem preenchidas.

Prevalence and risk factors for cervical intraepithelial neoplasia in HIV-infected women in Salvador, Bahia, Brazil / Prevalência e fatores de risco para neoplasia intraepitelial cervical em mulheres infectadas pelo HIV em Salvador, Bahia, Brasil

CONTEXT AND OBJECTIVE: The human immunodeficiency virus (HIV) is frequently associated with high-grade intraepithelial neoplasia. Immunosuppression and high HIV viral load are the main risk factors for cervical intraepithelial neoplasia (CIN). The aim of this study was to determine the prevalence of CIN in HIV-infected women in Salvador, Bahia, Brazil, and to describe the risk factors in comparison with non-infected women. DESIGN AND SETTING: Cross-sectional study at the AIDS Reference Center of Bahia and the Gynecological Outpatient Clinic of Fundação Bahiana para o Desenvolvimento da Ciência, in Salvador, Bahia, Brazil. METHODS: Sixty-four HIV-infected women and 76 uninfected women from Salvador were enrolled between May 2006 and May 2007. Associations between CIN and presence of HIV infection, HIV viral load, proportion of T CD4+ lymphocytes and risk factors were evaluated. The independence of the risk factors was investigated using logistic regression. RESULTS: CIN was more prevalent among HIV-infected women than in the control group (26.6 percent versus 6.6 percent; P = 0.01). The odds ratio for CIN among HIV-infected women was 3.7 (95 percent confidence interval, CI: 1.23-11; P = 0.01), after adjusting for the following variables: age at first sexual intercourse, number of partners, number of deliveries and previous history of sexually transmitted disease. CONCLUSION: The prevalence of CIN among HIV-infected women was significantly higher than among women without HIV infection. HIV infection was the most important risk factor associated with the development of cervical lesions.

CONTEXTO E OBJETIVO: O vírus da imunodeficiência humana (HIV) está frequentemente associado à neoplasia intraepitelial de alto grau. Imunossupressão e carga viral do HIV elevada são os principais fatores de risco para neoplasia intra-epitelial cervical (NIC). O objetivo deste estudo foi determinar a prevalência de NIC em mulheres infectadas pelo HIV, em Salvador, Bahia, Brasil e descrever os fatores de risco, comparando-as com mulheres não infectadas. TIPO DE ESTUDO E LOCAL: Estudo transversal no Centro de Referência de Aids da Bahia e Ambulatório de Ginecologia da Fundação Bahiana para o Desenvolvimento da Ciência, em Salvador, Bahia, Brasil. MÉTODOS: Foram incluídas no estudo 64 mulheres infectadas pelo HIV e 76 não infectadas provenientes de Salvador, no período de maio de 2006 a maio de 2007. Foi avaliada a associação entre NIC e presença da infecção pelo HIV, carga viral do HIV, proporção de linfócitos T CD4+ e fatores de risco. A independência dos fatores de risco foi verificada pela regressão logística. RESULTADOS: A prevalência de NIC foi maior nas mulheres infectadas pelo HIV que no grupo controle (26,6 por cento versus 6,6 por cento; P = 0,01). A razão de chances para NIC em mulheres infectadas pelo HIV foi 3,7 (95 por cento intervalo de confiança, IC: 1,23-11; P = 0,01) após ajuste das variáveis: idade da primeira relação sexual, número de parceiros, número de partos e história prévia de doença sexualmente transmissível. CONCLUSÃO: A prevalência de NIC foi significativamente maior em mulheres infectadas pelo HIV que naquelas não infectadas. A infecção pelo HIV foi o fator de risco mais importante associado com o desenvolvimento de lesões cervicais.

Imipramine induced elevation of prolactin levels in patients with HIV/AIDS improved their immune status / La elevación de niveles de prolactina mediante inducción con imipramina mejoró el estatus inmune de pacientes con VIH/SIDA

Prolactin is known to have significant immunomodulatory properties. Imipramine, a monoamine oxidase inhibitor, stimulates prolactin production because it decreases dopamine which inhibits secretion of prolactin. The study objective was to determine if use of imipramine can result in immunological benefits for HIV-positive patients by restoration and preservation of immunological function. A cohort of 19 retroviral positive patients was identified for the prospective study which continued for a 28-week period. Three patients dropped out before the study began. Inclusion criteria accepted only patients on the same highly active antiretroviral therapy (HAART) regimen for a nine-month period and who had reached a plateau with respect to the CD4 cell count and also had no prior history of antidepressant use for a 12-month period. This study had a "before and after" design, patients serving as their own control. The study drug imipramine was prescribed for a 12-week period up to visit 4, and then discontinued for 4-weeks (washout period) at which time blood investigations were done at visit 5. Finally, patients were prescribed the study drug for a further 12-week period to the end of the trial (visit 7). At the 95 per cent probability level, significant differences in average prolactin and CD4 levels from visit 4 to the end of the trial period were recorded. Results showed a trend of prolactin levels decreasing after washout (p = 0.015) and increasing by the end of the trial period once imipramine dispensation had recommenced (p = 0.006). With respect to the CD4 cell count, there was a significant increase after wash-out (p = 0.022). These results indicate a trend to immune boosting in HIV-positive patients who had obtained the maximum response from HAART.

Se sabe que la prolactina posee importantes propiedades inmunomudolatorias. La imipramina, un inhibidor de la monoamino oxidasa, estimula la producción de la prolactina porque disminuye la dopamina, que a su vez inhibe la secreción de prolactina. El objetivo de este estudio fue determinar si el uso de la imipramina puede traer beneficios inmunológicos a los pacientes VIH positivos mediante la restauración y preservación de la función inmunológica. Se identificó una cohorte de 19 pacientes retrovirales positivos, a fin de realizar este estudio prospectivo que continuó por un período de 28 semanas Tres pacientes se retiraron antes de que el estudio comenzara. Los criterios de inclusión aceptaban sólo pacientes que tuvieran el mismo régimen de terapia antiretroviral altamente activa (HAART) por un período de nueve meses, que hubieran alcanzado un nivel de estabilización con respecto al conteo de células CD4, y que no hubieran además tenido con anterioridad una historia de uso de anti-depresantes por espacio de 12 meses. Este estudio tuvo un diseño "antes y después", sirviendo los pacientes como su propio control. La imipramina para el estudio fue prescrita por un período de 12 semanas hasta la visita 4, y luego descontinuada por 4 semanas para un reposo farmacológico (período de lavado), realizándose entonces pruebas de sangre en la visita 5. Finalmente se prescribió el medicamento de estudio a los pacientes por un nuevo período de 12 semanas hasta el final del ensayo (visita 7). En el nivel de probabilidad del 95 por ciento, se registraron diferencias significativas en los niveles promedio de prolactina y CD4 desde la visita 4 hasta el final del período de ensayo. Los resultados mostraron una tendencia de los niveles de prolactina a descender tras el lavado (p = 0.015) y a aumentar hacia el final del período de ensayo, una vez que la dispensación de imipramina hubiese recomenzado (p = 0.006). Con respecto al conteo de células de CD4, hubo un aumento significativo luego del lavado (p = 0.022).

Difficulties reported by hiv-infected patients using antiretroviral therapy in brazil

OBJECTIVE: To describe the degree of difficulty that HIV-infected patients have with therapy treatment. INTRODUCTION: Patients' perceptions about their treatment are a determinant factor for improved adherence and a better quality of life. METHODS: Two cross-sectional analyses were conducted in public AIDS referral centers in Brazil among patients initiating treatment. Patients interviewed at baseline, after one month, and after seven months following the beginning of treatment were asked to classify and justify the degree of difficulty with treatment. Logistic regression was used for analysis. RESULTS: Among 406 patients initiating treatment, 350 (86.2 percent) and 209 (51.5 percent) returned for their first and third visits, respectively. Treatment perceptions ranged from medium to very difficult for 51.4 percent and 37.3 percent on the first and third visits, respectively. The main difficulties reported were adverse reactions to the medication and scheduling. A separate logistic regression indicated that the HIV-seropositive status disclosure, symptoms of anxiety, absence of psychotherapy, higher CD4+ cell count (> 200/mm³) and high (> 4) adverse reaction count reported were independently associated with the degree of difficulty in the first visit, while CDC clinical category A, pill burden (> 7 pills), use of other medications, high (> 4) adverse reaction count reported and low understanding of medical orientation showed independent association for the third visit. CONCLUSIONS: A significant level of difficulty was observed with treatment. Our analyses suggest the need for early assessment of difficulties with treatment, highlighting the importance of modifiable factors that may contribute to better adherence to the treatment protocol.

Comparison of the effectiveness of initial combined antiretroviral therapy with nelfinavir or efavirenz at a university-based outpatient service in Brazil

Since there are some concerns about the effectiveness of highly active antiretroviral therapy in developing countries, we compared the initial combination antiretroviral therapy with zidovudine and lamivudine plus either nelfinavir or efavirenz at a university-based outpatient service in Brazil. This was a retrospective comparative cohort study carried out in a tertiary level hospital. A total of 194 patients receiving either nelfinavir or efavirenz were identified through our electronic database search, but only 126 patients met the inclusion criteria. Patients were included if they were older than 18 years old, naive for antiretroviral therapy, and had at least 1 follow-up visit after starting the antiretroviral regimen. Fifty-one of the included patients were receiving a nelfinavir-based regimen and 75 an efavirenz-based regimen as outpatients. Antiretroviral therapy was prescribed to all patients according to current guidelines. By intention-to-treat (missing/switch = failure), after a 12-month period, 65 percent of the patients in the efavirenz group reached a viral load <400 copies/mL compared to 41 percent of the patients in the nelfinavir group (P = 0.01). The mean CD4 cell count increase after a 12-month period was also greater in the efavirenz group (195 x 10(6) cells/L) than in the nelfinavir group (119 x 10(6) cells/L; P = 0.002). The efavirenz-based regimen was superior compared to the nelfinavir-based regimen. The low response rate in the nelfinavir group might be partially explained by the difficulty of using a regimen requiring a higher patient compliance (12 vs 3 pills a day) in a developing country.

Impacto da Haart na prevalência de otite média crônica em crianças brasileiras infectadas pelo HIV / Haart impact on prevalence of chronic otitis media in Brazilian HIV-infected children

O advento de novas drogas anti-retrovirais como os inibidores de protease provocou mudanças sensíveis na morbidade e mortalidade de pacientes infectados pelo HIV. OBJETIVOS: Avaliar o impacto das novas drogas anti-retrovirais (Highly Active Anti-retroviral Therapy - HAART) na prevalência de otite média crônica em população pediátrica infectada pelo HIV. MÉTODOS: Analisamos os prontuários de 471 crianças com idade entre zero e 12 anos e 11 meses portadoras de HIV atendidas no ambulatório de AIDS de Clínica Otorrinolaringológica do HCFMUSP. As crianças foram divididas em dois grupos, de acordo com a faixa etária: 0 a 5 anos e 11 meses e 6 a 12 anos e 11 meses, e classificadas como portadoras de otite média crônica, baseadas em achados de anamnese, otoscopia, audiometria e imitanciometria. As prevalências de otite média crônica apresentadas e as contagens de linfócitos T CD4+ foram comparadas entre as crianças em uso ou não de HAART. RESULTADOS: Das 459 crianças atendidas, 65 (14,2 por cento) apresentavam otite média crônica. Observamos, nas crianças de 0 a 5 anos e 11 meses que o uso de HAART esteve associado a significante menor prevalência de otite média crônica (p = 0,02), e maior contagem de linfócitos T CD4+ (p < 0,001). CONCLUSÃO: O uso de HAART esteve associado à menor prevalência da forma crônica de otite média entre crianças menores de 6 anos infectadas pelo HIV, provavelmente como conseqüência do aumento promovido na contagem de linfócitos T CD4+.

The advent of new antiretroviral drugs such as protease inhibitors has generated sensible changes in morbity and mortality in HIV-infected patients. OBJECTIVES: To evaluate the impact of Highly Active Antiretroviral Therapy (HAART) on the prevalence of chronic otitis media in HIV-infected pediatric population. METHODS: We analyzed medical charts of 471 children aged zero to 12 years and 11 months with HIV infection from an Ambulatory of ENT and AIDS. Children were divided according to the age: 0 to 5 years and 11 months and 6 to 12 years and 11 months and classified as having chronic otitis media based on history, physical examination, audiologic and tympanometric data. Prevalence of chronic otitis media, as well as CD4+ lymphocyte count were compared between groups in use of HAART and the group without HAART. RESULTS: Out of 459 children, 65 (14.2 percent) had chronic otitis media. We observed that in children aged 0 to 5 years and 11 months who were taking HAART there was significant lower prevalence of chronic otitis media (p = 0.02). The use of HAART was associated to higher mean CD4+ lymphocyte count (p < 0.001). CONCLUSION: The use of HAART was associated to reduction in prevalence of chronic otitis media in HIV infected children, probably due to increase in mean CD4+ lymphocyte count.

Predictors of undetectable plasma viral load in HIV-positive adults receiving antiretroviral therapy in Southern Brazil

Factors associated with undetectable viral load (<80 copies/ml) were investigated among non-pregnant adults in antiretroviral treatment in a specialized service for HIV/AIDS in Southern Brazil. Use of antiretrovirals was investigated in two interviews (one month interval). Clinical data were collected from the clinical records; viral load previous to adherence measurement was defined the viral load previous to the first interview; the final viral load, the viral load subsequent to the second interview (interval between measures approximately 6 months). Undetectable final viral load occurred in 48 of the patients and was positively associated with levels of treatment adherence (p<0.001), being 19 for less than 60 of adherence and about 60 for adherence greater than 80. In the multivariate model, the odds of undetectable final viral load was four times greater for 80-94 and > or =95 of adherence (CI 95 1,80-13,28; CI 95 1,73-9,53), compared with less than 60 adherence; it was greater for less than 6 months in treatment (OR = 3.37; CI 95 1.09-10.46); and smaller for viral load previous to adherence measurement 5.2 log10 (OR = 0.19; CI95 0.06-0.58), adjusted for these variables and sex, age, clinical status, current immune status, group of drugs and interval between the two measurements of viral load. The crude odds were lower for age 16-24 years and use of Nucleoside Analog Reverse Transcriptase Inhibitors only, but these effects were not significant in the multivariate model. There was no evidence of effect of sex, clinical status, current immune status, and changes in treatment regimen. Treatment adherence gave the largest effect. Motivational interventions directed at adherence may improve treatment effectiveness.