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Summary Background Dolutegravir has been widely available in Brazil since 2017. Following the signal that infants born to women with dolutegravir exposure at conception in Botswana had a higher risk of neural tube defects (NTDs), public health leaders initiated a national investigation to evaluate periconception dolutegravir exposure among all pregnant Brazilian women with HIV and its potential association with risk of NTDs, stillbirth, or miscarriage before 22 weeks (also called spontaneous abortion). Methods In this retrospective, observational, national, cohort study, we identified all women with pregnancies and possible dolutegravir exposure within 8 weeks of estimated date of conception between Jan 1, 2017, and May 31, 2018, and approximately 3:1 matched pregnant women exposed to efavirenz between Jan 1, 2015, and May 31, 2018, using the Brazilian antiretroviral therapy database. We did detailed chart reviews for identified women. The primary outcomes were NTD and a composite measure of NTD, stillbirth, or miscarriage. NTD incidences were calculated with 95% CI. The composite outcome was examined with logistic regression using propensity score matching weights to balance confounders. Findings Of 1427 included women, 382 were exposed to dolutegravir within 8 weeks of estimated date of conception. During pregnancy, 183 (48%) of 382 dolutegravir-exposed and 465 (44%) of 1045 efavirenz-exposed women received folic acid supplementation. There were 1452 birth outcomes. There were no NTDs in either dolutegravir-exposed (0, 95% CI 0–0·0010) or efavirenz-exposed groups (0, 95% CI 0–0·0036). There were 23 (6%) stillbirths or miscarriages in 384 dolutegravir-exposed fetuses and 28 (3%) in the 1068 efavirenz-exposed fetuses (p=0·0037). Logistic regression models did not consistently indicate an association between dolutegravir exposure and risk of stillbirths or miscarriages. After study closure, two confirmed NTD outcomes in fetuses with periconception dolutegravir exposure were reported to public health officials. An updated estimate of NTD incidence incorporating these cases and the estimated number of additional dolutegravir-exposed pregnancies between Jan 1, 2015 and Feb 28, 2019, is 0·0018 (95% CI 0·0005–0·0067). Interpretation Neither dolutegravir nor efavirenz exposure was associated with NTDs in our national cohort; incidence of NTDs is probably well under 1% in dolutegravir-exposed HIV-positive women but still slightly above HIV-uninfected women (0·06%) in Brazil. Funding The Brazilian Ministry of Health and the United States’ National Institutes of Health.

Background In Brazil there are 926,742 people living with HIV/AIDS (PLWHA). Despite the introduction of antiretroviral therapy (ART) in 1996 and treatment for all in 2014, mortality has increased in some regions. This study aimed to estimate the factors associated with overall mortality in PLWHA to recommend public health actions. Methods We studied PLWHA aged ≥18 years old, followed-up from 2007 to 2015 in the universal health system in Brazil. We used a national database (disease reporting, laboratory tests, ART and death notifications). Kaplan-Meier method and Cox model were used in survival analysis. The outcome was all-cause deaths. The explanatory variables measured at baseline were sociodemographic characteristics, HIV transmission mode and coinfections by hepatitis B (HBV) and C (HCV). The time-varying variables were CD4 cell count, viral load (VL) and ART status. Results Study population (n = 411,281) was mainly male (61%), under 40 years old (61%), Caucasian (37%), with basic education (43%), heterosexual HIV-infection mode (41%), resident in Southeast region (48%). The co-infection rate was 2.5% for HCV, and 1.4% for HBV. Median time to ART initiation was 83 days. During the follow-up period (median: 4 years), 61,757 deaths occurred (6% HCV-coinfected and 2% HBV-coinfected). The global mortality rate was 3.44 [95% confidence interval: 3.42-3.47] per 100 person-years (PY) during 1,793,417 PY. The factors associated with increased mortality in multivariable analyses were male gender, age over 40, non-Caucasian race, HIV infection by drug use, resident in North, Northeast and South regions, HCV and HBV coinfection, VL ≥ 200 copies/mL and starting ART with CD4 Conclusions Although PLWHA start ART in less than 3 months after the beginning of follow-up, there is still late treatment (at CD4 Key messages The results of our study show that all populations should be target for HIV screening regardless of risk group. PLWHA coinfected with hepatitis B and hepatitis C should be also early treated for hepatitis coinfections.

Objective: To analyze the pattern of spatial distribution of hepatitis B virus (HBV) cases and the mortality attributed to this disease throughout the Brazilian territory, in 2005, 2016 and 2017. Methods: This is an ecological study of spatial analysis, using data from the Information System for Notifiable Diseases and the Brazilian Mortality Information System. HBV detection and mortality rates were analyzed. The spatial analysis from 2005 to 2017 was held through the Global Moran’s Index (I) for global data and the Local Indicators of Spatial Association (LISA) for the 5,564 municipalities of the country. Results: The North region stands out with the highest HBV detection and mortality rates in the country. The Global Moran’s I showed a spatial correlation of HBV cases in Brazil, and the LISA Map evidenced the presence of hotspots or spatial clusters (high-high type), mainly in the North region and also in some municipalities of Santa Catarina, Paraná, Rio Grande do Sul, Espírito Santo, São Paulo and Rio de Janeiro. Conclusion: The spatial analysis of the HBV distribution pattern in Brazil shows areas with a large concentration of cases, particularly in the North of the country and in other points distributed throughout the national territory. These data reinforce the urgency of intervention actions related to prevention, diagnosis and treatment of hepatitis B. RESUMO Objetivo: Analisar o padrão de distribuição espacial dos casos de hepatite causada pelo vírus B (HBV) e a mortalidade atribuída a esse agravo em todo o território nacional, nos anos de 2005, 2016 e 2017. Métodos : Trata-se de um estudo ecológico de análise espacial, utilizando dados do Sistema de Informação de Agravos de Notificação e do Sistema Nacional de Mortalidade. Analisaram-se as taxas de detecção e mortalidade de HBV. A análise espacial no período de 2005 a 2017 foi realizada por meio do Índice Global de Moran para os dados globais e dos Indicadores Locais de Associação Espacial (Lisa) para os 5.564 municípios do país. Resultados : A região Norte destaca-se pelas maiores taxas de detecção e mortalidade de HBV do país. O Índice Global de Moran revelou uma correlação espacial dos casos de HBV no Brasil, e o Lisa Map evidenciou a presença de bolsões (tipo high-high), principalmente na região Norte e também em alguns municípios de Santa Catarina, Paraná, Rio Grande do Sul, Espírito Santo, São Paulo e Rio de Janeiro. Conclusão : A análise espacial do padrão de distribuição do HBV no Brasil revela áreas com grande concentração de casos, particularmente no Norte do país e em outros pontos distribuídos pelo território nacional. Esses dados reforçam a urgência de ações de intervenção relativas a prevenção, diagnóstico e tratamento da hepatite B.

Nesta dissertação estudamos percolação em um grafo cuja quantidade de aglomerados abertos infinitos possui três fases nãotriviais, correspondentes à existência de nenhum, infinitos ou um único aglomerado. Esse grafo, denominado L, é construído a partir do produto diretode uma árvore regular T com linha Z, no qual cada elo da árvore está aberto com probabilidade t e cada élo da linha, com probabilidade Y. Todo o trabalho desenvolvido aqui seconstitui de uma análise específica do artigo Percolation in + 1 Dimensions, de Grimmett e Newman, cujo objetivo principal é definir como se comportam as curvas que dividem as três regiões, representativas das três fases no quadrado unitári, aprtir dos possíveis valaores do para ordenado(t,y). In this work we study percolation on a graph for which the number of in nite open clusters presents three non-trivial phases, corresponding to the existence of zero, in nite or a unique cluster. This graph, called L, is the direct product of a regular tree T and the line Z, in which each \tree" edge is open with probability and each \line" edge with probability Y. All work developed here is a speci c analysis of the article Percolation in 1+1 Dimensions, by Grimmett e Newman, whose the main purpose is de ne the behavior of the curves that divide the three regions, representative of three phases in the unit square, from the possible values of the ordered pair ((t,y).