Pacientes coinfectados com HIV e Hepatite B e /ou C : aspectos clínicos, epidemiológicos, subtipagem do HIV-1 e impacto na evolução clínica para a Aids

Orientadora: Drª. Sonia Mara RaboniDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Medicina Interna. Defesa : Curitiba, 11/06/2014Inclui referênciasÁrea de concentração: Doenças infecciosasResumo: A infecção pelo vírus da imunodeficiência humana tipo 1 (HIV-1) é um processo crônico caracterizado pela replicação viral contínua no hospedeiro. A alta taxa de replicação e elevado tamanho da população viral resulta subpopulações de vírus no mesmo indivíduo infectado denominado de quasispecies. O HIV-1, o vírus da hepatite B (HBV) e a hepatite C (HCV) podem ser diagnosticados em um mesmo paciente, pois compartilham rotas similares de transmissão, induzindo um pior prognóstico, e conduzindo a uma rápida evolução da infecção pelos vírus HBV e HCV. Apesar do seu impacto na qualidade de vida dos pacientes HIV positivo, informações sobre a coinfecção do HIV e hepatite virais no Hospital de Clínicas da Universidade Federal do Paraná são escassas. Este estudo descreveu as características demográficas, o perfil clínico e caracterização do HIV-1 de pacientes coinfectados com HIV e hepatites B ou C. Realizou-se estudo transversal com 93 pacientes HIV positivos nos ambulatórios de referência do HC-UFPR no período de março de 2011 a março de 2013. Dados clínicos, demográficos e epidemiológicos foram pesquisados em revisão de registros médicos, questionário e entrevistas com pacientes, a avaliação dos subtipos do HIV-1 foi feita por caracterização genética das regiões gag e vpu-env do vírus analisado a partir de amostras de sangue periférico pela metodologia de sequenciamento e análise filogenética. Foi encontrada sorologia positiva tanto para o HBV quanto para o HCV em 6,6% dos pacientes monitorados, com predominância do sexo masculino (65%) sendo a média de idade entre os pacientes de 45 anos (IQR 40 a 52). O teste sorológico anti-HCV foi positivo em 79/93 (85%) indivíduos, e a infecção foi confirmada por Reação em cadeia da polimerase (PCR) em 72% dos casos, com uma maior frequência do genótipo 1a/b. Dezoito pacientes (19%) eram HIV/HBV (HBsAg +). A avaliação genotípica do HIV-1 revelou os seguintes subtipos: subtipo B (2), C (8) BC (7) e subtipo BF (1) para a região gag; subtipo B (4), C (7), BC (8) e subtipo BF (8) na região vpu. Entre o pacientes coinfectados, houve uma alta frequência de uso de drogas (50%) e as investigações para a detecção de coinfecção foram tardias com diferença de 4 anos entre o diagnóstico do HIV e das hepatites. Um baixo número de pacientes era elegível para o tratamento e, embora a resposta à terapia antirretroviral tenha sido boa, houve um resposta muito pobre ao tratamento das hepatites. Considerando o aumento da sobrevida de pacientes HIV positivos e da alta frequência de coinfecção com hepatite, estes resultados preliminares indicara a necessidade de protocolos destinados à investigação sistemática de pacientes portadores do HIV, buscando, assim, a detecção precoce e tratamento dos indivíduos coinfectados. Palavras-chave: Vírus da imunodeficiência humana, hepatite B, hepatite C, coinfecção.Abstract: The human immunodeficiency virus type 1 (HIV-1) infection is a chronic process characterized by continuous viral replication in the host. The high replication level and the elevated viral population size results in subpopulation of virus in the infected person, called quasispecies. HIV-1, HBV and HCV coinfection can be diagnosed in the same patient, because these viruses share similar transmission routes, inducing a worst prognostic, leading to a rapid HBV and HCV infection evolution. Despites of its impact in life quality of HIV patients, information about HIV- HBV or HCV coinfection at HC-UFPR is scarce. This study describes the demographic characteristics, the clinical profile and the characterization of HIV-1 subtypes of HIV-HBC or HBV coinfected patients. It was carries out sectional study that icnluded 93 HIV positives out patients from HC-UFPR reference clinics from March 2011 to March 2013. Clinical, demographic and epidemiological data were evaluated by reviewing of medical registers, questionnaire and interviews with patients; HIV-1 subtype evaluation carried out by madenucleotide sequencing of gag and vpu-env viral regions. Positive serology for both HBV and HCVwas found in 6.6% of the patients monitored, with predominance of male (65%) and the average age of the patients was 45 (IQR 40-52). A anti-HCV test was positive in 79/93 (85%) of the individuals and the infection was confirmed by PCR in 72% of the cases, with a higher frequency of genotype 1a/b. Eighteen patients (19%) were HIV/HBV (HBsAg+). The HIV-1 genotypic evaluation revealed the followed subtypes: subtype B (2), C (8) BC (7) and subtype BF (1) for gag region; subtype B (4), C (7), BC (8) and subtype BF (8) for vpu region. Among coinfected patients, there was a high frequency of drug use (50%) and the investigations for detection of coinfection were conducted late with a difference of 4 years between HIV and hepatitis diagnostic. A low number of patients were eligible for the treatment, although the antiretroviral therapy response was adequate; there was a very poor response to hepatitis treatment. Considering the high survival of HIV patients and the high frequency of hepatitis coinfection, our preliminaries results indicate the need of protocols destined to systematic investigation of HIV patients, seeking of an earlier detection and treatment of coinfected patients. Keywords: Human immunodeficiency virus, hepatitis B, hepatitis C, coinfection

Leucemia Linfóide aguda em crianças : revisão histórica, diagnóstico e alternativas de tratamento

Orientadora: Dorly de Freitas BuchiCo-orientadora: Ana Paula Ressetti AbudMonografia (especialização) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Curso de Especialização em Biologia Celular e TecidualInclui referência

Human immunodeficiency virus and hepatitis C virus/hepatitis B virus co-infection in Southern Brazil: clinical and epidemiological evaluation

AbstractHepatitis B virus, hepatitis C virus and human immunodeficiency virus share a similar transmission pathway and are often diagnosed in the same patient. These patients tend to have a faster progression of hepatic fibrosis. This cross-sectional study describes the demographic features and clinical profile of human immunodeficiency virus/hepatitis co-infected patients in Paraná, Southern Brazil. A total of 93 human immunodeficiency virus-infected patients attending a tertiary care academic hospital in Southern Brazil were included. Clinical, demographic and epidemiological data were evaluated. Hepatitis B virus and/or hepatitis C virus positive serology was found in 6.6% of patients. The anti-hepatitis C virus serum test was positive in 85% (79/93) of patients, and the infection was confirmed in 72% of the cases. Eighteen patients (19%) were human immunodeficiency virus/hepatitis B virus positive (detectable HBsAg). Among co-infected patients, there was a high frequency of drug use, and investigations for the detection of co-infection were conducted late. A low number of patients were eligible for treatment and, although the response to antiretroviral therapy was good, there was a very poor response to hepatitis therapy. Our preliminary findings indicate the need for protocols aimed at systematic investigation of hepatitis B virus and hepatitis C virus in human immunodeficiency virus-infected patients, thus allowing for early detection and treatment of co-infected patients

Profile of HIV subtypes in HIV/HBV- and HIV/HCV-coinfected patients in Southern Brazil

Abstract INTRODUCTION: HIV and viral hepatitis infections are major causes of chronic disease worldwide and have some similarities with regard to routes of transmission, epidemiology, front barriers faced during access of treatment, and strategies for a global public health response. The objective was to describe the HIV-1 subtypes, viral tropism and single-nucleotide polymorphisms (SNPs) of interleukin 28B (IL28B) from a case series of HIV/viral hepatitis coinfected patients from southern Brazil. METHODS: Clinical and epidemiological data were evaluated by a review of medical records. Periodic blood draws were taken to determine the viral and host characteristics. RESULTS: This study included 38 patients with HIV/HBV or HIV/HCV coinfection; the median age was 49 years. Thirty-seven (97.4%) were on antiretroviral therapy, 32 (84.2%) had an undetectable viral load, a median CD4+ T-cell count of 452 cells/mm3. HIV-1 subtyping showed 47.4 and 31.6% of patients with subtypes C and B, respectively. Analysis of viral co-receptor usage showed a predominance of the R5 variant (64.7%), with no significant difference between the subtypes. Twenty patients with HIV/HCV coinfection were eligible to receive HCV therapy with pegylated-interferon-alpha plus ribavirin, and 10/20 (50%) of them achieved sustained virological response. SNPs of IL28B were evaluated in 93.3% of patients with HIV/HCV coinfection, and 17 (60.7%) presented the CC genotype. CONCLUSIONS: In the present case series, a higher frequency of HIV subtype C was found in coinfected patients. However such findings need to be prospectively evaluated with the inclusion of data from regional multicenter analyses