A Phase III, randomized study to evaluate the immunogenicity and safety of an MF59®-adjuvanted A/H1N1 pandemic influenza vaccine in HIV-positive adults

AbstractBackground and aimsAntibody responses to vaccines are suboptimal in immunosuppressed HIV-positive individuals. This study aimed to evaluate the potential benefits of MF59® adjuvant or a second A/H1N1 influenza vaccine dose in HIV-positive adults.MethodHIV-positive adults (n=61) and HIV-negative controls (n=93) aged 18–60years received two doses of A/H1N1, either as MF59-adjuvanted A/H1N1 pandemic vaccine, or as part of a unadjuvanted seasonal influenza vaccine containing the pandemic strain. Immunogenicity was assessed against the vaccine strain, A/California/7/2009, by haemagglutination inhibition (HI) assay three weeks after the administration of each vaccine dose. Local and systemic reactions were recorded for three days after each vaccination. Unsolicited adverse events were recorded throughout the six-week study period.ResultsBoth adjuvanted and unadjuvanted vaccines met the European licensure criteria in HIV-positive and HIV-negative study groups after a single dose. Lower antibody titres were observed with both adjuvanted and unadjuvanted vaccine in HIV-positive compared to HIV-negative subjects. A second dose of either vaccine did not compensate for the lower response of HIV-infected subjects. In HIV-positive subjects, CD4+ T cell counts and levels of CD38 expression on CD8+ T cells remained stable throughout the study period. Both vaccine formulations were generally well tolerated, with no increased reactogenicity observed in response to the adjuvanted vaccine.ConclusionAntibody responses in HIV-positive subjects were acceptable but lower than those in healthy control subjects, whether subjects were immunized with one or two doses of adjuvanted or unadjuvanted vaccine. Vaccination did not affect rates of HIV replication, CD4+ T cells counts, or levels of CD38 expression among patients under successful antiretroviral treatment

Nutritional and clinical status, and dietary patterns of people living with HIV/AIDS in ambulatory care in Sao Paulo, Brazil

INTRODUÇÃO: Atualmente, a abordagem nutricional desempenha papel essencial no tratamento de pessoas que vivem com HIV/aids, particularmente no caso de alterações metabólicas pelo uso da terapia antirretroviral (TARV) que podem estar associadas ao maior risco de doenças cardiovasculares (DCV). OBJETIVO: Caracterizar o estado nutricional, clínico e a qualidade da dieta de pessoas que vivem com HIV/aids. METODOLOGIA: Trata-se de um estudo transversal envolvendo pessoas que vivem com HIV/aids em atendimento na rede de serviços especializados no município de São Paulo. Os usuários desta rede, em uso ou não de TARV, foram recrutados no período de dezembro de 2004 a maio de 2006, durante consultas de rotina. Foram coletados dados sociodemográficos, clínicos, bioquímicos, antropométricos e dietéticos. A qualidade da dieta foi avaliada segundo escores de padrão de consumo predominantemente "não protetor" e "protetor" para DCV. RESULTADOS: A amostra foi constituída por 238 pacientes em TARV e 76 sem TARV. A média dos níveis de colesterol total, triglicérides e glicemia foram maiores no grupo TARV (p < 0,001). A maior parte dos participantes do estudo, com e sem TARV, apresentava-se eutrófica, com média de índice de massa corporal 24,4 (± 4,3) e 24,3 (± 3,5) kg/m², respectivamente. A relação cintura-quadril foi maior entre homens em TARV que entre aqueles sem TARV (0,90 ± 0,06 versus 0,87 ± 0,05) (p < 0,001). O grupo em TARV apresentou média de escores indicativa de maior consumo de alimentos "não protetores" para DCV (p = 0,001). CONCLUSÃO: Foram evidenciadas condições nutricionais e metabólicas indesejáveis entre aqueles em TARV, predisponentes ao risco de DCV. É apontada a necessidade de direcionamento das intervenções em saúde a pessoas que vivem com HIV/aids, para o controle dos fatores associados a essas doenças antes do desfecho final.INTRODUCTION: Nutrition currently plays a key role in the treatment of people living with HIV/AIDS (PLHA), especially in the case of metabolic alterations due to highly active antiretroviral therapy (HAART), which could be related to cardiovascular diseases (CD). OBJECTIVE: to describe the nutritional and clinical status, and the quality of diet of PLHA. METHODS: It is a cross-sectional study involving a network of ambulatory care facilities for PLHA in the city of São Paulo, Brazil. Patients, in use of HAART or not, were selected from December 2004 to may 2006, through routine clinic visits. We collected: socio-demographic, clinical, biochemical, anthropometric measures and dietary data. Diet quality was evaluated according to a "protecting" or "non-protecting" pattern of consumption scores for CD. RESULTS: The sample had 238 patients on HAART and 76 without treatment. Mean serum levels of total cholesterol, triglycerides and glucose were higher in the HAART group (p < 0.001). The majority of patients of both the treated and untreated group were eutrophic with a mean body mass index (BMI) of 24.4 (± 4.3) kg/m² and 24.3 (± 3.5), respectively. The waist-hip ratio was higher among men on HAART (0.90 ± 0.06 versus 0.87±0.05) (p < 0.001). The HAART group showed a mean food pattern score indicating a higher consumption of "non-protecting" foods for CD (p = 0.001). CONCLUSION: The results showed undesired nutritional and metabolic conditions among patients on HAART associated with CD. It is necessary to manage health intervention programs for PLHA in order to control cardiovascular risk factors before final outcomes.UNESCO - Ministério da Saúd

Barriers to treatment of hepatitis C in HIV/HCV coinfected adults in Brazil

The objective of this study was to assess the prevalence of barriers to interferon treatment in a population of HIV/HCV coinfected patients. A cross-sectional study was conducted at two AIDS Outpatient Clinics in Brazil. the study included all HIV infected patients followed at these institutions from January 2005 to November 2007. Medical records of 2,024 HIV-infected patients were evaluated. the prevalence of anti-HCV positive patients among them was 16.7%. Medical records of HCV/HIV coinfected patients were analyzed. 189 patients with the following characteristics were included in our study: mean age 43 years; male gender 65%; former IDUs (52%); HCV genotype 1 (66.4%); HCV genotype 3 (30.5%); median CD4+ T cell count was 340 cells/mm(3). Among 189 patients included in the analyses, only 75 (39.6%) were considered eligible for HCV treatment. the most frequent reasons for non-treatment were: non-compliance during clinical follow-up (31.4%), advanced HIV disease (21.9%), excessive alcohol consumption or active drug use (18.7%), and psychiatric disorders (10.1%). Conclusions: in Brazil, as in elsewhere, more than half of HIV/HCV coinfected patients (60.4%) have been considered not candidates to received anti-HCV treatment. the main reasons may be deemed questionable: non-adherence, drug abuse, and psychiatric disease. Our results highlight the importance of multidisciplinary teams to optimize the access of coinfected patients to HCV treatment.Fac Med ABC, Infect Dis Res Unit, São Paulo, BrazilAIDS Outpatient Clin, São Paulo, BrazilUniversidade Federal de São Paulo, AIDS Outpatient Clin, Fac Med, São Paulo, BrazilUniversidade Federal de São Paulo, AIDS Outpatient Clin, Fac Med, São Paulo, BrazilWeb of Scienc

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p 465 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.Univ Sao Paulo, Fac Med, Dept Molestias Infecciosas & Parasitarias, Sao Paulo, SP, BrazilUniv Fed Rio de Janeiro, Rio De Janeiro, RJ, BrazilCtr Referencia & Treinamento DST Aids, Sao Paulo, SP, BrazilCDH, Rio De Janeiro, RJ, BrazilHosp Fed Servidores Estado Rio de Janeiro HFSE, Setor Gastrohepatol, Rio De Janeiro, RJ, BrazilUniv Sao Paulo, Fac Med, Dept Gastroenterol & Hepatol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Disciplina Gastroenterol, EPM, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Disciplina Infectol, Sao Paulo, SP, BrazilUniv Sao Paulo, FMRP, Dept Clin Med, Div Gastroenterol, Sao Paulo, SP, Brazil| Univ Fed do Maranhao UFMA, HUPD, Ctr Pesquisa Clin, Sao Luis, MA, BrazilUniv Fed Estado Rio de Janeiro UNIRIO, Disciplina Clin Med & Gastroenterol, Rio De Janeiro, RJ, BrazilUniv Fed Rio do Grande Sul UFRGS, Dept Med Interna, Porto Alegre, RS, BrazilUniv Fed Espirito Santo, Ambulatorio HIV AIDS Hepatites Virais, Vitoria, ES, BrazilSMS, Ctr Orientacao & Aconselhamento, Foz Do Iguacu, PR, BrazilUniv Estado Rio de Janeiro UERJ, Serv Gastroenterol, Rio De Janeiro, RJ, BrazilIMT, Lab Virol LIM 52, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Disciplina Gastroenterol, EPM, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, EPM, Disciplina Infectol, Sao Paulo, SP, BrazilWeb of Scienc

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%,

Immunological effects of oral Lactobacillus casei Shirota among HIV-infected patients on suppressive antiretroviral treatment with poor CD4+ T cell recovery

Introdução: O tecido linfoide gastrointestinal é o principal reservatório de células T humanas e a depleção de células T CD4 + intestinais após a infecção pelo HIV leva a uma persistente disfunção da barreira mucosa, aumento da permeabilidade intestinal e translocação microbiana mesmo entre pacientes infectados pelo HIV em tratamento antirretroviral supressivo. Alguns estudos sugerem que os probióticos podem ajudar a restaurar a função intestinal. Métodos: Estudo randomizado duplo-cego, controlado por placebo, em pacientes adultos vivendo com HIV em terapia supressora e com baixa recuperação de LTCD4 +, para abordar o efeito do uso diário de 12 semanas de Lactobacillus casei Shirota oral na contagem de células T CD4 +, relação CD4 / CD8, ativação imune e avaliação do microbioma em 6 e 12 semanas de uso do composto ativo, e 12 semanas após a interrupção. Resultados: De jan / 2015 a jul / 2016, 48 pacientes foram randomizados para intervenção ativa (n = 24) ou placebo (n = 24). Os grupos tinham características demográficas e clínicas comparáveis; apenas o nadir de células T CD4 + foi estatisticamente diferente entre os grupos. Usando modelos mistos não ajustados, a intervenção foi associada com aumento médio de 58,8 células / mL em células TCD4 + nas visitas 6, 12 e 24 (IC 95% -11 a 129, p = 0,099) e aumento de 0,18 na relação CD4 / CD8 (IC 95% 0,03 a 0,33, p = 0,020). No entanto, essa diferença foi perdida após o ajuste para o nadir de células T CD4 +. Na visita 12, não foram encontradas diferenças significativas nos marcadores de ativação imune nas subpopulações CD4 + e CD8 +, níveis de sCD14 ou células NK entre os grupos. A avaliação do microbioma demonstrou um aumento estatisticamente significativo na família Bacteroidaceae na semana 12 (média 12,52% IC95% 5,89-19,06) em comparação com o valor basal (média 6,99%, IC 1,84-12,13; p=0,0422) restrito ao grupo que recebeu o composto ativo. Conclusão: Não encontramos nenhum efeito estatisticamente significativo do uso de Lactobacillus casei Shirota na contagem de células TCD4 + ou ativação imune entre pacientes vivendo com o HIV em terapia supressiva com baixa recuperação de LT CD4 +Background: Gastrointestinal lymphoid tissue is the main human T-cell reservoir and depletion of intestinal CD4+ T cells following HIV infection leads to persisting mucosal barrier disfunction, increased gut permeability and microbial translocation even among HIV-infected patients on suppressive antiretroviral treatment. Some suggest probiotics may help restore intestinal function. Methods: In this double-blind, placebo-controlled trial, we enrolled adult HIVinfected patients on suppressive ART with poor CD4+ recovery to address the effect of a 12-week daily use of oral Lactobacillus casei Shirota on CD4+ T cell count, CD4/CD8 ratio, immune activation and microbiome analysis at 6 and 12 weeks on study product, and 12 weeks after interruption. Results: From Jan/2015 to Jul/2016, 48 patients were randomized to active intervention (n=24) or placebo (n=24). Groups had comparable demographic and clinical characteristics; only CD4+ T cell nadir was statistically different between groups. All participants were virologically-suppressed under antiretroviral treatment. Using unadjusted mixed models, the intervention was associated with mean increase of 58.8 cells/mL in post-baseline CD4+ cells at visits 6, 12 and 24 (95%CI -11 to 129, p=0.099) and 0.18 increase in CD4/CD8 ratio (95%CI 0.03 to 0.33, p=0.020). However, this difference was lost following adjustment for CD4+ T cell nadir. At visit 12, no significant differences in immune activation markers on CD4+ and CD8+ subpopulations, sCD14 levels or NK cells were found between groups. Microbiome analysis showed a statistically significant increase in the Bacteroidaceae family at week 12 (mean 12.52% CI 95% 5.89-19.06) compared to baseline (mean 6.99%, CI 1.84-12 , 13; p = 0.0422) restricted to the group that received the active compound Conclusions: We found no statistically significant effect of Lactobacillus casei Shirota probiotic on CD4+ T cell counts or immune activation among HIVinfected patients on suppressive ART with poor CD4+ recover

Response predictors to treatment with pegylated interferon in chronic hepatitis B

The clinical and epidemiological importance of chronic B hepatitis is currently unquestionable as a cause of end-stage liver disease and hepatocellular carcinoma. Recently, predictors of treatment response of this disease have been studied, both before and during the course of medication. Therapy stopping rules have been proposed, which may be useful in patients presenting poor treatment tolerance. This review discusses the treatment response predictors usefulness, with emphasis on ALT, quantitative HBsAg and HBeAg, quantitative HBV-DNA and HBV genotyp

BAIXA PREVALÊNCIA DE NÃO RESPOSTA VIROLÓGICA NO RESGATE ANTIRRETROVIRAL E FATORES ASSOCIADOS EM UMA COORTE DE PACIENTES VIVENDO COM HIV-1 COM FALHA VIROLÓGICA E RESISTÊNCIA A MÚLTIPLOS ANTIRRETROVIRAIS

Terapias de resgate foram pouco estudados no atendimento clínico de rotina, fora das condições de um estudo randomizado. O objetivo do nosso estudo foi analisar a taxa de não resposta ao tratamento antirretroviral, em pacientes multiexperimentados a antirretrovirais, recebendo esquema de resgate. Análise retrospectiva de prontuários. Foram considerados respondedores ao tratamento de resgate aqueles pacientes que obtiveram carga viral indetectável em até 24 semanas após introdução do esquema de resgate antirretroviral. A análise de resistência foi baseada em teste de genotipagem. Os fatores analisados foram: sexo, idade, carga viral e CD4 no início do tratamento de regate, tempo de negativação da carga viral entre os respondedores, comorbidades associadas, infecções oportunistas prévias, histórico antirretroviral, número de medicamentos ativos no esquema e uso de novas classes. Os dados foram analisados no programa estatístico STATA versão 13.0 (StataCorp LP, CollegeStation, Texas, USA). Cento e quarenta pacientes multiexperimentados, no período de julho de 2008 a março de 2016. No basal, foi observado LT CD4+ superior a 200 células/mm3 em 52,1% dos pacientes e carga viral inferior a 100 mil cópias/mL em 50,7%. O número médio de falhas prévias foi de 5 (1-12 falhas), com uma média de 159 meses do diagnóstico de infecção pelo HIV. Ao resgate, aproximadamente metade dos pacientes receberam 3 ou 4 medicamentos ativos. Cento e doze (80,0%) utilizaram novas classes. Cento e trinta e um (93,5%) foram considerados respondedores ao tratamento de resgate. O tempo médio para resposta foi de 6,7 meses. Nove pacientes continuaram com a carga viral detectável após o tratamento de resgate (Prevalência: 6,4%; [IC 95% 3,0 - 11,9]). Na análise bivariada os fatores associados significativamente à não resposta foram: etilismo (p = 0,048), menos de 2 medicamentos ativos no resgate (p = 0,007) e LT CD4+ prévio inferior a 200 células/mm3 ao resgate (p = 0,017). Na regressão logística múltipla LT CD4+ inferior a 200 células/mm3, previamente ao resgate, e a utilização de menos de dois medicamentos ativos no resgate foi independentemente associado à não resposta virológica. Pacientes multiexperimentados e com resistência antirretroviral, submetidos à terapia de resgate apresentaram alta taxa de resposta virológica, sendo que LT CD4+ inferior a 200 cél/mm3 prévios ao resgate e uso de menos de dois medicamentos ativos foram independentemente associados falha terapêutica