Prevalence and Associated Factors of Cryptococcal Antigenemia in HIV-Infected Patients with CD4 < 200 Cells/µL in São Paulo, Brazil: A Bayesian Analysis

Cryptococcosis is a severe life-threatening disease and a major cause of mortality in people with advanced AIDS and CD4 ≤ 100 cells/µL. Considering the knowledge gap regarding the benefits of routine application of antigenemia tests in HIV-infected patients with 100−200 CD4 cells/µL for the prevention of cryptococcal meningitis (CM), we aimed to evaluate the prevalence of positive antigenemia through lateral flow assay (LFA) and associated factors in HIV-infected patients with CD4 < 200 cells/µL. Our findings of 3.49% of positive LFA (LFA+) patients with CD4 < 100 cells/µL and 2.24% with CD4 between 100−200 cells/µL have been included in a Bayesian analysis with 12 other studies containing similar samples worldwide. This analysis showed a proportion of 3.6% LFA+ patients (95% credible interval-Ci [2.5−5.7%]) with CD4 < 100 cells/µL and 1.1% (95%Ci [0.5−4.3%]) with CD4 between 100−200 cells/µL, without statistical difference between these groups. The difference between mortality rates in LFA+ and negative LFA groups was e = 0.05013. Cryptococcoma and CM were observed in the LFA+ group with 100−200 and <100 CD4 cells/µL, respectively. Considering the benefits of antifungal therapy for LFA+ patients, our data reinforced the recommendation to apply LFA as a routine test in patients with 100−200 CD4 cells/µL aiming to expand cost-effectiveness studies in this group.

Humoral and cellular immune responses to CoronaVac up to one year after vaccination.

Coronavac is a widely used SARS-CoV-2 inactivated vaccine, but its long-term immune response assessment is still lacking. We evaluated SARS-CoV-2-specific immune responses, including T cell activation markers, antigen-specific cytokine production and antibody response following vaccination in 53 adult and elderly individuals participating in a phase 3 clinical trial. Activated follicular helper T (Tfh), non-Tfh and memory CD4+ T cells were detected in almost all subjects early after the first vaccine dose. Activated memory CD4+ T cells were predominantly of central and effector memory T cell phenotypes and were sustained for at least 6 months. We also detected a balanced Th1-, Th2- and Th17/Th22-type cytokine production that was associated with response over time, together with particular cytokine profile linked to poor responses in older vaccinees. SARS-CoV-2-specific IgG levels peaked 14 days after the second dose and were mostly stable over one year. CoronaVac was able to induce a potent and durable antiviral antigen-specific cellular response and the cytokine profiles related to the response over time and impacted by the senescence were defined.

Humoral and cellular immune responses to CoronaVac assessed up to one year after vaccination.

Background: The Sinovac SARS-CoV-2 inactivated vaccine (CoronaVac) has been demonstrated to be safe, well tolerated, and efficacious in preventing mild and severe Covid-19. Although different studies have demonstrated its short-term immunogenicity, long-term cellular and humoral response evaluations are still lacking. Methods: Cellular and humoral responses were assessed after enrollment of volunteers in the PROFISCOV phase 3 double-blind, randomized, placebo-controlled clinical trial to evaluate CoronaVac. Assays were performed using flow cytometry to evaluate cellular immune response and an antigen binding electrochemiluminescence assay to detect antigen-specific antibodies to the virus. Results: Fifty-three volunteers were selected for long term assessment of their SARS-CoV-2-specific immune responses. CD4 + T cell responses (including circulating follicular helper (cTfh, CD45RA - CXCR5 + ) expressing CD40L, as well as non-cTfh cells expressing CXCR3) were observed early upon the first vaccine dose, increased after the second dose, remaining stable for 6-months. Memory CD4 + T cells were detected in almost all vaccinees, the majority being central memory T cells. IgG levels against Wuhan/WH04/2020 N, S and receptor binding domain (RBD) antigens and the variants of concern (VOCs, including B.1.1.7/Alpha, B.1.351/Beta and P.1/Gamma) S and RBD antigens peaked 14 days after the second vaccine shot, and were mostly stable for a 1-year period. Conclusions: CoronaVac two-doses regimen is able to induce a potent and durable SARS-CoV-2 specific cellular response. The cellular reaction is part of a coordinated immune response that includes high levels of specific IgG levels against parental and SARS-CoV-2 VOC strains, still detected after one year. Funding: Fundação Butantan, Instituto Butantan and São Paulo Research Foundation (FAPESP) (grants 2020/10127-1 and 2020/06409-1). This work has also been supported by NIH contract 75N93019C00065 (A.S, D.W). PATH facilitated reagent donations for this work with support by the Bill & Melinda Gates Foundation (INV-021239). Under the grant conditions of the foundation, a Creative Commons Attribution 4.0 generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.

Access and adherence to isoniazid preventive therapy and occurrence of active TB in a cohort of people living with HIV: a retrospective cohort study in Sao Paulo, Brazil.

Tuberculosis (TB) is still a leading cause of morbidity and mortality among people living with HIV (PLHIV). The diagnosis of latent TB is required for the implementation of prophylactic therapy with isoniazid (PTI). However, low access to diagnosis of latent TB and non-adherence to PTI may hinder potential benefits of this essential intervention. In this study, we addressed the access and adherence to PTI in a cohort of PLHIV with positive tuberculin skin test (TST) in a reference HIV clinic in Sao Paulo, Brazil. We have also analyzed the occurrence of active TB over a median of 131 months after a positive TST among study participants. Our findings revealed that 88.3% of the 238 TST-positive patients had access to PTI, and 196 (93.3%) of those with access adhered to PTI. Active tuberculosis was diagnosed in three of the 196 TST-positive patients who adhered to PTI (1.5%; 95% confidence interval [CI] 0.3-4.4%), whereas seven cases were detected among 42 patients without access or who did not adhere to PTI (16.6%; 95% CI 7.0-31.3%). The apparent beneficial effect of PTI in our cohort is consistent with previous studies including PLHIV, and highlights the importance of reliably delivering each of the steps between screening for latent TB and provision of PTI.

HIV-infected youths transitioning from pediatric to adult outpatient care in a teaching tertiary care hospital in São Paulo city, Brazil.

BACKGROUND: HIV-infected children surviving until adulthood have been transitioning to adult outpatient health care service in Brazil since the late 2000's. Deterioration of clinical condition is expected during this period, as reported among youths with non-communicable chronic diseases. Despite their young age, they are long-term hosts of the virus, have prolonged exposure to antiretroviral therapy and have suffered from the social determinants and stigma of HIV infection since early childhood. OBJECTIVES: This study aimed to 1) describe demographic and clinical characteristics at the first appointment at adult care service following pediatric care of a cohort of Brazilian youths living with HIV since childhood; and 2) retrospectively address adherence and clinical variables in the last two years of pediatric follow-up. METHODS: Descriptive study. RESULTS: 41 consecutive patients referred to adult outpatient care from a pediatric HIV unit were enrolled, median age 19 years, and median lifetime CD4+nadir 117 cell/mm3; 89% reported previous AIDS-defining conditions. At first laboratory assessment in adult care, only 46% had undetectable (<400 copies/ml) HIV viral load and the median CD4+count was 250 cell/mm3. CONCLUSION: Youths living with HIV at the transition from pediatric to adult care had poor treatment adherence, low lifetime CD4+cell nadir, low CD4 cell count and detectable HIV viral load. Health care providers should closely monitor these adolescents in a youth friendly environment, prepared for open communication about all aspects of their health.

Systematic review of economic evaluations of the 23-valent pneumococcal polysaccharide vaccine (PPV23) in individuals 60 years of age or older.

OBJECTIVES: To systematically review the economic evaluations of 23-valent pneumococcal polysaccharide vaccine (PPV23) in adults aged ≥60 years to inform the development of local studies through the discussion of parameters and assumptions that influence the results of the analyses. METHODS: We searched the MEDLINE, Excerpta Medica, Cochrane Library, Latin-American and Caribbean Health Sciences Literature (LILACS), Brazilian Regional Library of Medicine, National Health Service Economic Evaluation, and Centre for Reviews and Dissemination-as well as the Scopus citation index and the Web of Science for full economic evaluations of PPV23 published up to March 2016. Two independent reviewers screened the articles for relevance and extracted the data. Main study characteristics and methods (clinical and epidemiological data, cost and incremental cost-effectiveness ratios (ICERs) were extracted and compared. Costs were updated to 2016 international dollars. RESULTS: Twenty-seven studies published from 1980 to 2016 were reviewed. Most studies were conducted in Europe and the USA; three studies were conducted in Latin America (Brazil, 2; Colombia, 1). In addition to the scenario comparing the vaccination with the PPV23 to non-vaccination, three studies also compared PPV23 to pneumococcal conjugate 13-valent vaccine (PCV13). All studies used static models. Most used a lifetime (44.4%) or 5-6 year's time horizon (33.3%). Only three studies considered herd protection from children immunization with PCV13 in the model. Most studies considered PPV23 cost-effective (less than US$50,000 per LYG or QALY) and sometimes cost-saving (results ranging from cost-saving to US$84,636/QALY). The estimates of disease burden, the efficacy/effectiveness of PPV23, and the effects of herd protection from childhood immunization had most influence on the results. CONCLUSIONS: Well-designed cost-effectiveness studies of PPV23 that represent the current epidemiological scenario and reduce uncertainty related to efficacy/effectiveness are extremely relevant to informing the decision-making process.

Cost-Effectiveness Analysis of Universal Vaccination of Adults Aged 60 Years with 23-Valent Pneumococcal Polysaccharide Vaccine versus Current Practice in Brazil.

OBJECTIVE: To evaluate the cost-effectiveness of introducing universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) into the National Immunization Program (NIP) in Brazil. METHODS: Economic evaluation using a Markov model to compare two strategies: (1) universal vaccination of adults aged 60 years with one dose of PPV23 and 2) current practice (vaccination of institutionalized elderly and elderly with underlying diseases). The perspective was from the health system and society. Temporal horizon was 10 years. Discount rate of 5% was applied to costs and benefits. Clinical syndromes of interest were invasive pneumococcal disease (IPD) including meningitis, sepsis and others and pneumonia. Vaccine efficacy against IPD was obtained from a meta-analysis of randomized control trials and randomized studies, whereas vaccine effectiveness against pneumonia was obtained from cohort studies. Resource utilization and costs were obtained from the Brazilian Health Information Systems. The primary outcome was cost per life year saved (LYS). Univariate and multivariate sensitivity analysis were performed. RESULTS: The universal vaccination strategy avoided 7,810 hospitalizations and 514 deaths, saving 3,787 years of life and costing a total of USD$31,507,012 and USD$44,548,180, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$1,297 per LYS, from the perspective of the health system, and USD$904 per LYS, from the societal perspective. CONCLUSION: The results suggest that universal vaccination of adults aged 60 years with the 23-valent pneumococcal polysaccharide vaccine (PPV23) is a very cost-effective intervention for preventing hospitalization and deaths for IPD and pneumonia is this age group in Brazil.

High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil

OBJECTIVES: To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS: Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors ± raltegravir ± enfuvirtide ± maraviroc) after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS: Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6). The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2). At week 48, 83% (95% CI: 75-90%) had an HIV RNA level <50 copies/mL and the median CD4 cell count was 301 (interquartile range 224-445) cells/mm³. Baseline HIV RNA >100 000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p = 0.028). CONCLUSIONS: Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.

High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil.

OBJECTIVES: To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS: Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors ± raltegravir ± enfuvirtide ± maraviroc) after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS: Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6). The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2). At week 48, 83% (95% CI: 75-90%) had an HIV RNA level <50 copies/mL and the median CD4 cell count was 301 (interquartile range 224-445) cells/mm(3). Baseline HIV RNA >100000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p=0.028). CONCLUSIONS: Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.

Pertussis booster vaccine for adolescents and young adults in São Paulo, Brazil / Avaliação de reforços vacinais contra a coqueluche para adolescentes e adultos na cidade de São Paulo / Evaluación de refuerzos vacunales contra la tosferina para adolescentes y adultos en la ciudad de Sao Paulo, Sureste de Brasil

OBJECTIVE: To develop a model to assess different strategies of pertussis booster vaccination in the city of São Paulo. METHODS: A dynamic stationary age-dependent compartmental model with waning immunity was developed. The "Who Acquires Infection from Whom" matrix was used to modeling age-dependent transmission rates. There were tested different strategies including vaccine boosters to the current vaccination schedule and three of them were reported: (i) 35 percent coverage at age 12, or (ii) 70 percent coverage at age 12, and (iii) 35 percent coverage at age 12 and 70 percent coverage at age 20 at the same time. RESULTS: The strategy (i) achieved a 59 percent reduction of pertussis occurrence and a 53 percent reduction in infants while strategy (ii) produced 76 percent and 63 percent reduction and strategy (iii) 62 percent and 54 percent, respectively. CONCLUSION: Pertussis booster vaccination at age 12 proved to be the best strategy among those tested in this study as it achieves the highest overall reduction and the greatest impact among infants who are more susceptible to pertussis complications.

OBJETIVO: Desenvolver um modelo capaz de acessar resultados de diferentes possíveis estratégias de reforço vacinal contra a coqueluche, na cidade de São Paulo. MÉTODOS: O modelo matemático dinâmico proposto é dependente da idade e considerou perda da imunidade vacinal com o avanço da idade. A matriz "who acquire infection from whom" foi utilizada para inserir as diferentes dinâmicas de contatos entre os grupos etários. Diferentes estratégias vacinais foram testadas, acrescentando reforços vacinais ao atual esquema utilizado, e três diferentes estratégias foram reportadas: (i) 35 por cento ou (ii) 70 por cento de cobertura vacinal na idade de 12 anos e (iii) coberturas vacinais de 35 por cento aos 12 anos e 70 por cento aos 20 anos ao mesmo tempo. RESULTADOS: A estratégia (i) produziu redução de 59 por cento nos casos de coqueluche e 53 por cento de redução entre os menores de um ano; a estratégia (ii) alcançou redução de 76 por cento nos casos e de 63 por cento entre os menores de um ano; a estratégia (iii) reduziu em 62 por cento o total de casos e 54 por cento entre os menores de um ano. DISCUSSÃO: Reforço vacinal contra a coqueluche aos 12 anos é a melhor estratégia dentre as testadas, pois gera maior redução de casos em todas as idades e alcança maior impacto entre os menores de um ano, os mais vulneráveis às complicações da coqueluche.

OBJETIVO: Desarrollar un modelo capaz de acceder resultados de diferentes posibles estrategias de refuerzo vacunal contra la tosferina, en la ciudad de Sao Paulo, Sureste de Brasil. MÉTODOS: El modelo matemático dinámico propuesto es dependiente de la edad y consideró pérdida de la inmunidad vacunal con el avance de la edad. La matriz "who acquire infection from whom" fue utilizada para insertar las diferentes dinámicas de contactos entre los grupos de edad. Diferentes estrategias vacunales fueron evaluadas, añadiendo refuerzos vacunales al actual esquema utilizado, e tres diferentes estrategias fueron reportadas: (i) 35 por ciento o (ii) 70 por ciento de cobertura vacunal en la edad de 12 años e (iii) coberturas vacunales de 35 por ciento a los 12 años y 70 por ciento a los 20 años al mismo tiempo. RESULTADOS: La estrategia (i) produjo reducción de 59 por ciento en los casos de tosferina y 53 por ciento de reducción entre los menores de un año; la estrategia (ii) alcanzó reducción de 76 por ciento en los casos y de 63 por ciento entre los menores de un año; la estrategia (iii) redujo en 62 por ciento el total de casos y 54 por ciento entre los menores de un año. DISCUSIÓN: Refuerzo vacunal contra la tosferina a los 12 años es la mejor estrategia entre las evaluadas, pues genera mayor reducción de casos en todas las edades y alcanza mayor impacto entre los menores de un año, los mas vulnerables a las complicaciones de la tosferina.

Pertussis booster vaccine for adolescents and young adults in São Paulo, Brazil.

OBJECTIVE: To develop a model to assess different strategies of pertussis booster vaccination in the city of São Paulo. METHODS: A dynamic stationary age-dependent compartmental model with waning immunity was developed. The "Who Acquires Infection from Whom" matrix was used to modeling age-dependent transmission rates. There were tested different strategies including vaccine boosters to the current vaccination schedule and three of them were reported: (i) 35% coverage at age 12, or (ii) 70% coverage at age 12, and (iii) 35% coverage at age 12 and 70% coverage at age 20 at the same time. RESULTS: The strategy (i) achieved a 59% reduction of pertussis occurrence and a 53% reduction in infants while strategy (ii) produced 76% and 63% reduction and strategy (iii) 62% and 54%, respectively. CONCLUSION: Pertussis booster vaccination at age 12 proved to be the best strategy among those tested in this study as it achieves the highest overall reduction and the greatest impact among infants who are more susceptible to pertussis complications.

Avaliação de novas estratégias vacinais contra a coqueluche no município de São Paulo / Theoretical evaluation of new vaccination strategies in São Paulo

Introdução: A coqueluche é caracterizada por tosse paroxística, pode levar menores de um ano de idade ao óbito, deixar seqüelas e exacerbar quadros respiratórios crônicos. A imunidade após a doença ou vacina não é para toda a vida. Nos países desenvolvidos, apesar de altas coberturas vacinais e do controle da doença entre as décadas de 50 e 80, desde o final dos anos 80 é observado o aumento dos casos em adolescentes, adultos e lactentes, sendo indicado o reforço vacinal para adolescentes e adultos. No Brasil a doença aparenta estar sob controle, mas há um estudo teórico que demonstra a possibilidade de aumento dos casos. Objetivo: Avaliar novas estratégias de reforço vacinal contra a coqueluche no município de São Paulo. Metodologia: Desenvolvimento de um modelo matemático determinístico, dinâmico e dependente da idade dos indivíduos. Simulações com o esquema vacinal atual e: (i) novo reforço aos 12 anos com coberturas vacinais de 10, 35, 45e 70; (ii) reforços aos 12 anos e aos 20 anos de idade, com 35e 70de cobertura, respectivamente. Introdução de contato heterogêneo da população com o uso de uma matriz de contato. Fontes dos dados: Banco de dados do Sistema Único de Saúde (DATASUS), Centro de Vigilância Epidemiológica da Secretaria de Estado da Saúde de São Paulo e a literatura nacional e internacional. Uso dos programas Berkeley Madonna® para resolução das equações diferenciais e Microsoft Excel® para o cálculo da matriz de contato e das forças de infecção.ao vacinar os adolescentes, inclusive com baixa cobertura vacinal, portanto tal estratégia demonstra-se promissora para o controle da coqueluche. Não houve ganho ao acrescentar apenas um reforço para os adultos (20 anos). Os resultados são concordantes com o que há na literatura e permitiram um primeiro panorama para auxiliar na abordagem do problema. Estudos com diferentes estratégias de vacinação de adultos e estudos de custo-benefício são recomendados.

Doença meningocógica: investigação de surto comunitário no distrito administrativo do Grajaú, município de São Paulo, julho de 2006 / meningococcical disease: communitarian outbreak investigation in Grajaú, in the city of São Paulo, july, 2006

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Adolescência e aids: avaliaçäo de uma experiência de educaçäo preventiva entre pares / Adolescence and Aids: evaluation of a preventive education experience among peers

Açöes preventivas de HIV/AIDS, orientadas à superaçäo dos limites das intervençöes de corte comportamentalista, incorporando preocupaçöes com os determinantes sócio-culturais desses comportamentos, constituem hoje uma necessidade e, ao mesmo tempo, uma lacuna. O presente artigo trata de estudo de prevençäo no ambiente escolar baseado em estratégia de reduçäo de vulnerabilidade. Constitui um estudo de caso, de corte quanti-quali, que, no contexto desta estratégia, avalia o trabalho de prevençäo de aids desenvolvido por alunos multiplicadores em uma escola estadual de ensino médio na periferia da cidade de Säo Paulo. Entre os resultados, destacam-se: a efetividade da proposta, com ampla aceitaçäo e favorável aproveitamento pelos alunos da escola; o perfil diversificado do aluno multiplicador voluntário; e a tensäo entre modelos cognitivo-comportamentalistas e social-construtivistas nos processos educativos concretamente operados pelos multiplicadores. Conclui-se pela possibilidade e interesse da açäo de alunos multiplicadores na perspectiva das estratégias de reduçäo de vulnerabilidade, apontando-se a necessidade de desenvolver mecanismos de captaçäo e capacitaçäo capazes de problematizar e superar a tensäo apontada.