Introduction of human gammaherpesvirus 8 genotypes A, B, and C into Brazil from multiple geographic regions

Variations in the open reading frame (ORF) K1 gene sequence of human gammaherpesvirus 8 (HHV-8) has led to the identification of 6 major genotypic clades (A, B, C, D, E, and F) in specimens isolated from around the world. These clades exhibit clear clustering among individuals in different ethnic groups and from different geographic regions. The human population of Brazil varies greatly in ethnicity because of multiple immigration events from Africa, Europe, Asia, and indigenous communities. However, there is scant information about the HHV-8 genotypes currently circulating in Brazil. Here, we describe HHV-8 genotypic diversity in isolates from Brazilian HIV-infected patients living with Kaposi's sarcoma (KS) by analysis of the complete ORF-K1 region. We also identified the most likely geographic origins of these different Brazilian genotypes. We extracted HHV-8 DNA (24 positive samples) from individuals with HIV/KS from the states of São Paulo and Rio de Janeiro, amplified the ORF-K1 gene using nested PCR (about 870 base pairs), performed sequencing and phylogenetic analysis, and then calculated the mean genetic distances of Brazilian sequences from sequences in other regions of the world (523 sequences analyzed). Phylogenetic analysis showed that genotypes C, A, and B were present in 45.8 %, 29.2 % and 25 % of the isolates from Brazil, respectively. These isolates grouped into separate clades, rather than a single monophyletic cluster. Mean genetic distance analyses suggested that these genotypes were introduced into the Brazil multiple times from different geographical regions. HHV-8/A isolates appear to be from Ukraine, Russia, and the Tartar ethnic group; HHV-8/B isolates appear to be from Congo and Democratic Republic of the Congo; and HHV-8/C isolates appear to be from Australia, Algeria, England, and French Guiana. These results contribute to a better understanding of the genetic diversity and origins of HHV-8 strains circulating in Brazil, and will provide a foundation for further epidemiological and evolutionary studies of HHV-8

Prevalência de sarcoma de Kaposi em pacientes com aids e fatores associados, São Paulo-SP, 2003-2010 / Prevalencia de sarcoma de Kaposi en pacientes con SIDA y factores asociados, São Paulo-SP, Brasil, 2003-2010 / Prevalence of Kaposi's sarcoma in patients with AIDS and associated factors, São Paulo-SP, Brazil, 2003-2010

OBJETIVO: estimar a prevalência de sarcoma de Kaposi (SK) em pacientes com aids e identificar os fatores associados à ocorrência da neoplasia. MÉTODOS: estudo transversal com dados de notificação em dois centros de referência em aids de São Paulo-SP, Brasil, de janeiro/2003 a março/2010; empregaram-se métodos de linkage probabilístico e regressão logística múltipla. RESULTADOS: entre 3.557 casos de aids, 213 (6%) apresentavam SK, 95,3% deles do sexo masculino; associaram-se à ocorrência de SK sexo masculino (OR=3,1; IC95%=1,4;6,6), idade no momento do diagnóstico de aids >28 anos (OR=1,6; IC95%=1,0; 2,6), homens que fazem sexo com homens (OR=3,2; IC95%=2,0;4,9), uso prévio de terapia antirretroviral de alta atividade (HAART) (OR=0,4; IC95%=0,3;0,5), período de diagnóstico de aids de 2007-2010 (OR=0,3; IC95%=0,2;0,4) e contagem de linfócitos T CD4+ <200cel/mm³ (OR=16,0; IC95%=6,0;42,7) e 200-500cel/mm³ (OR=2,5; IC95%=1,1;6,4). CONCLUSÃO: o SK tem alta prevalência em São Paulo-SP; estratégias para o diagnóstico precoce do HIV podem resultar em diminuição desta prevalência.

OBJETIVO: estimar la prevalencia del sarcoma de Kaposi (SK) en pacientes con SIDA e identificar los factores asociados. MÉTODOS: estudio transversal para identificar la asociación entre el SK y SIDA en São Paulo-SP, Brasil; los datos se obtuvieron entre enero de 2003 y marzo de 2010 y se analizaron con el método de linkage probabilística y regresión logística múltipla. RESULTADOS: en 3.557 casos de SIDA, la prevalencia de SK fue 6%; entre los 213 casos de SK, el 95,3% eran varones; estuvieron asociados con SK el sexo masculino (OR=3,1; IC95%=1,4;6,6), la edad >28 años (OR=1,6; IC95%=1,01;2,5 2,6), HSH (OR=3,2; IC95%= 2,0;4,9), el uso previo de HAART (OR=0,4; IC95%=0,3;0,5), diagnóstico de SIDA en 2007-2010 (OR=0,3 IC95%=0,2;0,4) y células T CD4+ <200cel/mm3 (OR=16,0; IC95%=6,0;42,7) y 200-500cel/mm³ (OR=2,5 IC95%=1,1;6,4). CONCLUSIÓN: el SK tiene una alta prevalencia en São Paulo-SP; las estrategias para el diagnóstico precoz del VIH pueden reducirlo.

OBJECTIVE: to estimate the prevalence of Kaposi's sarcoma (KS) in patients with AIDS and identify the associated factors to the occurrence of this neoplasm. METHODS: this is a cross-sectional study with notification data from two AIDS reference centers in São Paulo-SP, Brazil, from January, 2003 to March, 2010; probabilistic linkage and multiple logistic regression methods were applied. RESULTS: among 3,557 AIDS cases, 213 (6%) presented KS; 95.3% of them occurred in males; male sex (OR=3.1; 95%CI=1.4;6.6), age at the AIDS diagnosis >28 years old (OR=1.6; 95%CI=1.0;2.6), MSM (OR=3.2; 95%CI=2.0;4.9), prior use of HAART (OR=0.4; 95%CI=0.3;0.5), AIDS diagnosis between 2007-2010 (OR=0.3; 95%CI=0.2;0.4), and CD4+ T-cell counting under 200cells/mm3 (OR=16.0; 95%CI=6.0;42.7) and 200-500cells/mm³ (OR=2,5; 95%CI=1.1;6.4) were associated to the occurrence of KS. CONCLUSION: KS has a high prevalence in São Paulo-SP; strategies for early HIV diagnosis may reduce this prevalence.

Prevalence of Kaposi's sarcoma in patients with AIDS and associated factors, São Paulo-SP, Brazil, 2003-2010. / Prevalência de sarcoma de Kaposi em pacientes com aids e fatores associados, São Paulo-SP, 2003-2010.

OBJECTIVE: to estimate the prevalence of Kaposi's sarcoma (KS) in patients with AIDS and identify the associated factors to the occurrence of this neoplasm. METHODS: this is a cross-sectional study with notification data from two AIDS reference centers in São Paulo-SP, Brazil, from January, 2003 to March, 2010; probabilistic linkage and multiple logistic regression methods were applied. RESULTS: among 3,557 AIDS cases, 213 (6%) presented KS; 95.3% of them occurred in males; male sex (OR=3.1; 95%CI=1.4;6.6), age at the AIDS diagnosis >28 years old (OR=1.6; 95%CI=1.0;2.6), MSM (OR=3.2; 95%CI=2.0;4.9), prior use of HAART (OR=0.4; 95%CI=0.3;0.5), AIDS diagnosis between 2007-2010 (OR=0.3; 95%CI=0.2;0.4), and CD4+ T-cell counting under 200cells/mm3 (OR=16.0; 95%CI=6.0;42.7) and 200-500cells/mm³ (OR=2,5; 95%CI=1.1;6.4) were associated to the occurrence of KS. CONCLUSION: KS has a high prevalence in São Paulo-SP; strategies for early HIV diagnosis may reduce this prevalence.

Evolution of hepatitis B serological markers in HIV coinfected patients: a case study.

OBJECTIVE: To describe the evolution of serological markers among HIV and hepatitis B coinfected patients, with emphasis on evaluating the reactivation or seroreversion of these markers. METHODS: The study population consisted of patients met in an AIDS Outpatient Clinic in São Paulo State, Brazil. We included in the analysis all HIV-infected and who underwent at least two positive hepatitis B surface antigen serological testing during clinical follow up, with tests taken six months apart. Patients were tested with commercial kits available for hepatitis B serological markers by microparticle enzyme immunoassay. Clinical variables were collected: age, sex, CD4+ T-cell count, HIV viral load, alanine aminotransferase level, exposure to antiretroviral drugs including lamivudine and/or tenofovir. RESULTS: Among 2,242 HIV positive patients, we identified 105 (4.7%) patients with chronic hepatitis B. Follow up time for these patients varied from six months to 20.5 years. All patients underwent antiretroviral therapy during follow-up. Among patients with chronic hepatitis B, 58% were hepatitis B "e" antigen positive at the first assessment. Clearance of hepatitis B surface antigen occurred in 15% (16/105) of patients with chronic hepatitis B, and 50% (8/16) of these patients presented subsequent reactivation or seroreversion of hepatitis B surface antigen. Among hepatitis B "e" antigen positive patients, 57% (35/61) presented clearance of this serologic marker. During clinical follow up, 28.5% (10/35) of those who initially cleared hepatitis B "e" antigen presented seroreversion or reactivation of this marker. CONCLUSIONS: Among HIV coinfected patients under antiretroviral therapy, changes of HBV serological markers were frequently observed. These results suggest that frequent monitoring of these serum markers should be recommended.

Evolution of hepatitis B serological markers in HIV coinfected patients: a case study

ABSTRACT OBJECTIVE To describe the evolution of serological markers among HIV and hepatitis B coinfected patients, with emphasis on evaluating the reactivation or seroreversion of these markers. METHODS The study population consisted of patients met in an AIDS Outpatient Clinic in São Paulo State, Brazil. We included in the analysis all HIV-infected and who underwent at least two positive hepatitis B surface antigen serological testing during clinical follow up, with tests taken six months apart. Patients were tested with commercial kits available for hepatitis B serological markers by microparticle enzyme immunoassay. Clinical variables were collected: age, sex, CD4+ T-cell count, HIV viral load, alanine aminotransferase level, exposure to antiretroviral drugs including lamivudine and/or tenofovir. RESULTS Among 2,242 HIV positive patients, we identified 105 (4.7%) patients with chronic hepatitis B. Follow up time for these patients varied from six months to 20.5 years. All patients underwent antiretroviral therapy during follow-up. Among patients with chronic hepatitis B, 58% were hepatitis B “e” antigen positive at the first assessment. Clearance of hepatitis B surface antigen occurred in 15% (16/105) of patients with chronic hepatitis B, and 50% (8/16) of these patients presented subsequent reactivation or seroreversion of hepatitis B surface antigen. Among hepatitis B “e” antigen positive patients, 57% (35/61) presented clearance of this serologic marker. During clinical follow up, 28.5% (10/35) of those who initially cleared hepatitis B “e” antigen presented seroreversion or reactivation of this marker. CONCLUSIONS Among HIV coinfected patients under antiretroviral therapy, changes of HBV serological markers were frequently observed. These results suggest that frequent monitoring of these serum markers should be recommended.

Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma

Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50%) in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.

Consensus of the Brazilian Society of Infectious Diseases and Brazilian Society of Clinical Oncology on the management and treatment of Kaposi's sarcoma.

Kaposi's sarcoma is a multifocal vascular lesion of low-grade potential that is most often present in mucocutaneous sites and usually also affects lymph nodes and visceral organs. The condition may manifest through purplish lesions, flat or raised with an irregular shape, gastrointestinal bleeding due to lesions located in the digestive system, and dyspnea and hemoptysis associated with pulmonary lesions. In the early 1980s, the appearance of several cases of Kaposi's sarcoma in homosexual men was the first alarm about a newly identified epidemic, acquired immunodeficiency syndrome. In 1994, it was finally demonstrated that the presence of a herpes virus associated with Kaposi's sarcoma called HHV-8 or Kaposi's sarcoma herpes virus and its genetic sequence was rapidly deciphered. The prevalence of this virus is very high (about 50%) in some African populations, but stands between 2% and 8% for the entire world population. Kaposi's sarcoma only develops when the immune system is depressed, as in acquired immunodeficiency syndrome, which appears to be associated with a specific variant of the Kaposi's sarcoma herpes virus. There are no treatment guidelines for Kaposi's sarcoma established in Brazil, and thus the Brazilian Society of Clinical Oncology and the Brazilian Society of Infectious Diseases developed the treatment consensus presented here.