Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil.

BACKGROUND: The increased survival provided by the access, development, and evolution of antiretroviral drugs (ARV) greatly increased the life expectancy of people living with HIV (PWH). This has also led to an increased occurrence of diseases or morbidities related to aging. In individuals with multiple comorbidities, the simultaneous use of multiple medications, also known as polypharmacy, is common, and rational use of medications is essential. This study aims to describe the pharmacotherapeutic profile, estimate the prevalence of polypharmacy and identify factors associated with polypharmacy in a cohort of adult PWH from a referral unit in Rio de Janeiro, Brazil. METHODS: Cross-sectional study including PWH on ARV who received at least one medical prescription (outpatient/hospitalized) in 2019. We described the proportion of prescribed medications according to ARV and Anatomical Therapeutic Chemical (ATC) classes stratified by age (< 50 vs. ≥50 years). Polypharmacy was defined as ≥ 5 medications prescribed beyond ARV. Logistic regression models assessed demographic and clinical factors associated with polypharmacy. RESULTS: A total of 143,306 prescriptions of 4547 PWH were analyzed. Median age was 44.4 years (IQR:35.4-54.1) and 1615 (35.6%) were ≥ 50 years. A total of 2958 (65.1%) participants self-identified as cisgender man, 1365 (30.0%) as cisgender woman, and 224 (4.9%) as transgender women. Most self-declared Black/Pardo (2582; 65.1%) and 1984 (44.0%) completed elementary education or less. Median time since HIV diagnosis was 10.9 years (IQR:6.2-17.7). Most frequently prescribed concomitant medications were nervous system (64.8%), antiinfectives for systemic use (60.0%), alimentary tract and metabolism (45.9%), cardiovascular system (40.0%) and respiratory system (37.1%). Prevalence of polypharmacy was 50.6% (95%CI: 49.2-52.1). Model results indicated that being older, self-identify as cisgender woman, having less education and longer time since HIV diagnosis increased the odds of polypharmacy. CONCLUSIONS: We found high rates of polypharmacy and concomitant medication use in a cohort of PWH in Brazil. Targeted interventions should be prioritized to prevent interactions and improve treatment, especially among individuals using central nervous system and cardiovascular medications, as well as certain groups such as cisgender women, older individuals and those with lower education. Standardized protocols for continuous review of patients' therapeutic regimens should be implemented.

BestFLR Trial: Liver Regeneration at CT before Major Hepatectomies for Liver Cancer-A Randomized Controlled Trial Comparing Portal Vein Embolization with N-Butyl-Cyanoacrylate Plus Iodized Oil versus Polyvinyl Alcohol Particles Plus Coils.

Background In patients with liver cancer, portal vein embolization (PVE) is recommended to promote liver growth before major hepatectomies. However, the optimal embolization strategy has not been established. Purpose To compare liver regeneration as seen at CT in participants with liver cancer, before major hepatectomies, with N-butyl-cyanoacrylate (NBCA) plus iodized oil versus standard polyvinyl alcohol (PVA) particles plus coils, for PVE. Materials and Methods In this single-center, prospective, randomized controlled trial (Best Future Liver Remnant, or BestFLR, trial; International Standard Randomized Controlled Trial Number 16062796), PVE with NBCA plus iodized oil was compared with standard PVE with PVA particles plus coils in participants with liver cancer. Participant recruitment started in November 2017 and ended in March 2020. Participants were randomly assigned to undergo PVE with PVA particles plus coils or PVE with NBCA plus iodized oil. The primary end point was liver growth assessed with CT 14 days and 28 days after PVE. Secondary outcomes included posthepatectomy liver failure, surgical complications, and length of intensive care treatment and hospital stay. The Mann-Whitney U test was used to compare continuous outcomes according to PVE material, whereas the Χ2 test or Fisher exact test was used for categoric variables. Results Sixty participants (mean age, 61 years ± 11 [standard deviation]; 32 men) were assigned to the PVA particles plus coils group (n = 30) or to the NBCA plus iodized oil group (n = 30). Interim analysis revealed faster and superior liver hypertrophy for the NBCA plus iodized oil group versus the PVA particles plus coils group 14 days and 28 days after PVE (absolute hypertrophy of 46% vs 30% [P < .001] and 57% vs 37% [P < .001], respectively). Liver growth for the proposed hepatectomy was achieved in 87% of participants (26 of 30) in the NBCA plus iodized oil group versus 53% of participants (16 of 30) in the PVA particles plus coils group (P = .008) 14 days after PVE. Liver failure occurred in 13% of participants (three of 24) in the NBCA plus iodized oil group and in 27% of participants (six of 22) in the PVA particles plus coils group (P = .27). Conclusion Portal vein embolization with N-butyl-cyanoacrylate plus iodized oil produced greater and faster liver growth as seen at CT in participants with liver cancer, compared with portal vein embolization with polyvinyl alcohol particles plus coils, allowing for earlier surgical intervention. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Arellano in this issue.

Cost-effectiveness analysis of a quality improvement program to reduce caesarean sections in Brazilian private hospitals: a case study.

BACKGROUND: In 2015, a quality improvement project of childbirth care called Adequate Childbirth Project ("Projeto Parto Adequado"- PPA) was implemented in Brazilian public and private hospitals, aiming to improve the quality of childbirth care and to reduce caesarean sections without clinical indications. The objective of this study is to conduct an economic analysis of two models of care existing in a private Brazilian hospital-the model following the recommendations of the PPA and the standard of care model-in reducing the proportion of caesarean sections. METHODS: We conducted a cost-effectiveness analysis using data from one of the private hospitals included in the PPA project. The main outcome was the proportion of caesarean section. We used total cost of hospitalization for women and newborns, from the health care sector perspective, during the length of the observed hospital stay. We did not apply discount rates and inflation rate adjustments due to the short time horizon. We conducted univariate sensitivity analysis using the minimum and maximum costs observed in hospitalizations and variation in the probabilities of caesarean section and of maternal and neonatal complications. RESULTS: 238 puerperal women were included in this analysis. The PPA model of care resulted in a 56.9 percentage point reduction in the caesarean section probability (88.6% vs 31.7%, p < 0.001) with an incremental cost-effectiveness ratio of US$1,237.40 per avoided caesarean section. Women in the PPA model of care also had a higher proportion of spontaneous and induced labor and a lower proportion of early term births. There were no maternal, fetal or neonatal deaths and no significant differences in cases of maternal and neonatal near miss. The cost of uncomplicated vaginal births and caesarean sections was the parameter with the greatest impact on the cost-effectiveness ratio of the PPA model of care. CONCLUSION: The PPA model of care was cost-effective in reducing caesarean sections in women assisted in a Brazilian private hospital. Moreover, it reduced the frequency of early term births and did not increase the occurrence of severe negative maternal and neonatal outcomes.

AIDS and non-AIDS severe morbidity associated with hospitalizations among HIV-infected patients in two regions with universal access to care and antiretroviral therapy, France and Brazil, 2000-2008: hospital-based cohort studies.

BACKGROUND: In high-income settings, the spectrum of morbidity and mortality experienced by Human Immunodeficiency Virus (HIV)-infected individuals receiving combination antiretroviral therapy (cART) has switched from predominantly AIDS-related to non-AIDS-related conditions. In the context of universal access to care, we evaluated whether that shift would apply in Brazil, a middle-income country with universal access to treatment, as compared to France. METHODS: Two hospital-based cohorts of HIV-infected individuals were used for this analysis: the ANRS CO3 Aquitaine Cohort in South Western France and the Evandro Chagas Research Institute (IPEC) Cohort of the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Severe morbid events (AIDS- and non-AIDS-related) were defined as all clinical diagnoses associated with a hospitalization of ≥48 hours. Trends in the incidence rate of events and their determinants were estimated while adjusting for within-subject correlation using generalized estimating equations models with an auto-regressive correlation structure and robust standard errors. RESULT: Between January 2000 and December 2008, 7812 adult patients were followed for a total of 41,668 person-years (PY) of follow-up. Throughout the study period, 90% of the patients were treated with cART. The annual incidence rate of AIDS and non-AIDS events, and of deaths significantly decreased over the years, from 6.2, 21.1, and 1.9 AIDS, non-AIDS events, and deaths per 100 PY in 2000 to 4.3, 14.9, and 1.5/100 PY in 2008. The annual incidence rates of non-AIDS events surpassed that of AIDS-events during the entire study period. High CD4 cell counts were associated with a lower incidence rate of AIDS and non-AIDS events as well as with lower rates of specific non-AIDS events, such as bacterial, hepatic, viral, neurological, and cardiovascular conditions. Adjusted analysis showed that severe morbidity was associated with lower CD4 counts and higher plasma HIV RNAs but not with setting (IPEC versus Aquitaine). CONCLUSIONS: As information on severe morbidities for HIV-infected patients remain scarce, data on hospitalizations are valuable to identify priorities for case management and to improve the quality of life of patients with a chronic disease requiring life-long treatment. Immune restoration is highly effective in reducing AIDS and non-AIDS severe morbid events irrespective of the setting.

Clinical outcomes and risk factors for immune recovery and all-cause mortality in Latin Americans living with HIV with virological success: a retrospective cohort study.

INTRODUCTION: Immune reconstitution following antiretroviral therapy (ART) initiation is crucial to prevent AIDS and non-AIDS-related comorbidities. Patients with suppressed viraemia who fail to restore cellular immunity are exposed to an increased risk of morbidity and mortality during long-term follow-up, although the underlying mechanisms remain poorly understood. We aim to describe clinical outcomes and factors associated with the worse immune recovery and all-cause mortality in people living with HIV (PLWH) from Latin America following ART initiation. METHODS: Retrospective cohort study using the CCASAnet database: PLWH ≥18 years of age at ART initiation using a three drug-based combination therapy and with medical follow-up for ≥24 months after ART initiation and undetectable viral load were included. Patients were divided into four immune recovery groups based on rounded quartiles of increase in CD4 T-cell count at 2 years of treatment (<150, [150, 250), [250, 350] and >350 cells/mm3 ). Primary outcomes included all-cause mortality, AIDS-defining events and non-communicable diseases that occurred >2 years after ART initiation. Factors associated with an increase in CD4 T-cell count at 2 years of treatment were evaluated using a cumulative probability model with a logit link. RESULTS: In our cohort of 4496 Latin American PLWH, we found that patients with the lowest CD4 increase (<150) had the lowest survival probability at 10 years of follow-up. Lower increase in CD4 count following therapy initiation (and remarkably not a lower baseline CD4 T-cell count) and older age were risk factors for all-cause mortality. We also found that older age, male sex and higher baseline CD4 T-cell count were associated with lower CD4 count increase following therapy initiation. CONCLUSIONS: Our study shows that PLWH with lower increases in CD4 count have lower survival probabilities. CD4 increase during follow-up might be a better predictor of mortality in undetectable PLWH than baseline CD4 count. Therefore, it should be included as a routine clinical variable to assess immune recovery and overall survival.

Evaluation of Mpox Knowledge, Stigma, and Willingness to Vaccinate for Mpox: Cross-Sectional Web-Based Survey Among Sexual and Gender Minorities.

BACKGROUND: The 2022 multicountry mpox outbreak positioned the condition as a public health emergency of international concern. By May 2023, Brazil ranked second globally in the cumulative number of mpox cases and deaths. The higher incidence of mpox among gay and other men who have sex with men in the current mpox outbreak deepens the stigma and discrimination against sexual and gender minorities (SGM). This might worsen the structural barriers impacting access to health services, which ultimately leads to undertesting and underreporting of cases. There are no data available on mpox knowledge and stigma in Latin America. OBJECTIVE: We aimed to evaluate mpox knowledge, stigma, and willingness to vaccinate for mpox among SGM, and to describe sociodemographic and behavioral characteristics according to self-reported mpox diagnosis. METHODS: A cross-sectional, internet-based survey was conducted in a convenience sample of adults (aged >18 years) living in Brazil recruited through advertisements on dating apps, social media, referral institutions for infectious diseases websites, and mass media (October-November 2022). We compared participants' characteristics according to self-reported mpox diagnosis using chi-square test or Fisher exact test for qualitative variables and Kruskal-Wallis test for quantitative variables. RESULTS: We enrolled 6236 participants: 5685 (91.2%) were cisgender men; 6032 (96.7%) were gay, bisexual, or pansexual; 3877 (62.2%) were White; 4902 (78.7%) had tertiary education; and 4070 (65.2%) reported low or middle income. Most participants (n=5258, 84.4%) agreed or strongly agreed that "LGBTQIA+ individuals are being discriminated and stigmatized due to mpox." Mpox awareness was 96.9% (n=6044), and 5008 (95.1%) were willing to get vaccinated for mpox. Overall, 324 (5.2%) reported an mpox diagnosis. Among these, 318 (98.1%) reported lesions, 178 (56%) local pain, and 316 (99.4%) sought health care. Among participants not reporting a diagnosis, 288 (4.9%) had a suspicious lesion, but only 158 (54.9%) of these had sought health care. Compared to participants with no diagnosis, those reporting an mpox diagnosis were younger (P<.001), reported more sex partners (P<.001), and changes in sexual behavior after mpox onset (P=.002). Moreover, participants diagnosed with mpox reported more frequently being tested for HIV in the prior 3 months (P<.001), living with HIV (P<.001), currently using HIV pre-exposure prophylaxis (P<.001), and previous sexually transmitted infection diagnosis (P<.001). CONCLUSIONS: Our results point to high mpox knowledge and willingness to vaccinate among SGM in Brazil. Participants self-reporting mpox diagnosis more frequently reported to be living with HIV, STI diagnosis, and current pre-exposure prophylaxis use, highlighting the importance of an mpox assessment that includes comprehensive sexual health screenings. Efforts to decrease stigma related to mpox among SGM are necessary to avoid mpox underdiagnosis.

Preferences for pre-exposure prophylaxis (PrEP) among sexual and gender minorities: a discrete choice experiment in Brazil.

Background: Men who have sex with men (MSM) and transgender women (TGW) are disproportionally affected by HIV infection in Latin America. This study aims to assess pre-exposure prophylaxis (PrEP) preferences among sexual and gender minorities (SGM) and identify attributes and levels that are related to PrEP uptake and adherence, both crucial for PrEP success. Methods: We conducted a discrete choice experiment (DCE) among SGM from all Brazilian regions (September-December/2020). The survey was administered face-to-face (five Brazilian capitals) and online (entire country). We used a D-efficient zero-prior blocked experimental design to select 60 paired-profile DCE choice tasks. Findings: The total sample size was 3924 (90.5% MSM; 7.2% TGW and 2.3% non-binary or gender diverse persons). In random-effects logit models, highest levels of protection and "no side effects" were the most important attribute levels. For "presentation", injectable and implant were preferred over oral. Participants were willing to accept a 4.1% protection reduction to receive injectable PrEP or a 4.2% reduction if PrEP were taken monthly. The largest class in the latent class models was defined predominantly by the preference for the highest HIV protection level (p < 0.005). Respondents in this class also preferred no side effects, injectable and implant presentations. Interpretation: Higher HIV protection, no side effects, and presentation, whether injectable or implant, were the most important attributes in PrEP preferences. Protection against HIV was the most important attribute. PrEP programs should make available technologies such as long-acting presentations that could reunite the most desired attributes, thus maximizing acceptability and user-appropriateness. Funding: Unitaid.

The effectiveness of COVID-19 vaccines against severe cases and deaths in Brazil from 2021 to 2022: a registry-based study.

Background: Brazil started the COVID-19 mass vaccination in January 2021 with CoronaVac and ChAdOx1, followed by BNT162b2 and Ad26.COV2.S vaccines. By the end of 2021, more than 317 million vaccine doses were administered in the adult population. This study aimed at estimating the effectiveness of the primary series of COVID-19 vaccination and booster shots in protecting against severe cases and deaths in Brazil during the first year of vaccination. Methods: A cohort dataset of over 158 million vaccination and severe cases records linked from official national registries was analyzed via a mixed-effects Poisson model, adjusted for age, state of residence, time after immunization, and calendar time to estimate the absolute vaccine effectiveness of the primary series of vaccination and the relative effectiveness of the booster. The method permitted analysis of effectiveness against hospitalizations and deaths, including in the periods of variant dominance. Findings: Vaccine effectiveness against severe cases and deaths remained over 25% and 50%, respectively, after 19 weeks from primary vaccination of BNT162b2, ChAdOx1, or CoronaVac vaccines. The boosters conferred greater protection than the primary series of vaccination, with heterologous boosters providing marginally greater protection than homologous. The effectiveness against hospitalization during the Omicron dominance in the 60+ years old population started at 61.7% (95% CI, 26.1-86.2) for ChAdOx1, 95.6% (95% CI, 82.4-99.9) for CoronaVac, and 72.3% (95% CI, 51.4-87.4) for the BNT162b2 vaccine. Interpretation: This study provides real-world evidence of the effectiveness of COVID-19 vaccination in Brazil, including during the Omicron wave, demonstrating protection even after waning effectiveness. Comparisons of the effectiveness among different vaccines require caution due to potential bias effects related to age groups, periods in the pandemic, and eventual behavioural changes. Funding: Fundação Oswaldo Cruz (FIOCRUZ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), Pan American Health Organization (PAHO), Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde do Ministério da Saúde do Brasil (DECIT/SCTIE/MS).

Cervical cancer screening among HIV-infected women: an economic evaluation in a middle-income country.

Due to the recent widespread availability of highly active antiretroviral therapy (HAART) in middle-income countries, there has been an increase in life expectancy for women on HAART, but no corresponding decrease in cervical cancer incidence. This study evaluates the optimal cervical cancer screening strategy for HIV-infected women in a middle-income country. We developed a mathematical model, which simulates the natural history of the HPV infection, as well as the HIV-mediated immunosupression among women in Brazil. Our model was calibrated using data from the IPEC/FIOCRUZ Women's HIV-infected cohort. The model compares the lifetime effects, costs and cost-effectiveness of strategies combining cytology, HPV DNA test and colposcopy at different screening intervals for different CD4 count strata (27 strategies in total). We found that the strategy with the best cost-effectiveness profile (cost-effectiveness ratio-U$4,911/year of life saved [YLS] and probability of being cost-effective-86%) was HPV testing followed by cytology triage every year for all HIV infected women, considering a very cost-effective threshold given by Brazil's GDP per capita (US$8,625/YLS). The results were robust to changes in the input parameters as demonstrated in one-way, scenario, threshold and probabilistic sensitivity analysis. Our study indicates that annual HPV testing followed by cytology triage for all HIV-infected women is likely to be very cost-effective in a middle-income country like Brazil. The results reflect the synergic effect of using a highly sensitive screening test (HPV DNA test) in sequence with a highly specific test (cytology).

Dengue vector control strategies in an urban setting: an economic modelling assessment.

BACKGROUND: An estimated 2·5 billion people are at risk of dengue. Incidence of dengue is especially high in resource-constrained countries, where control relies mainly on insecticides targeted at larval or adult mosquitoes. We did epidemiological and economic assessments of different vector control strategies. METHODS: We developed a dynamic model of dengue transmission that assesses the evolution of insecticide resistance and immunity in the human population, thus allowing for long-term evolutionary and immunological effects of decreased dengue transmission. We measured the dengue health burden in terms of disability-adjusted life-years (DALYs) lost. We did a cost-effectiveness analysis of 43 insecticide-based vector control strategies, including strategies targeted at adult and larval stages, at varying efficacies (high-efficacy [90% mortality], medium-efficacy [60% mortality], and low-efficacy [30% mortality]) and yearly application frequencies (one to six applications). To assess the effect of parameter uncertainty on the results, we did a probabilistic sensitivity analysis and a threshold analysis. FINDINGS: All interventions caused the emergence of insecticide resistance, which, with the loss of herd immunity, will increase the magnitude of future dengue epidemics. In our model, one or more applications of high-efficacy larval control reduced dengue burden for up to 2 years, whereas three or more applications of adult vector control reduced dengue burden for up to 4 years. The incremental cost-effectiveness ratios of the strategies for two high-efficacy adult vector control applications per year was US$615 per DALY saved and for six high-efficacy adult vector control applications per year was $1267 per DALY saved. Sensitivity analysis showed that if the cost of adult control was more than 8·2 times the cost of larval control then all strategies based on adult control became dominated. INTERPRETATION: Six high-efficacy adult vector control applications per year has a cost-effectiveness ratio that will probably meet WHO's standard for a cost-effective or very cost-effective intervention. Year-round larval control can be counterproductive, exacerbating epidemics in later years because of evolution of insecticide resistance and loss of herd immunity. We suggest the reassessment of vector control policies that are based on larval control only. FUNDING: The Fulbright Programme, CAPES (Brazilian federal agency for post-graduate education), the Miriam Burnett trust, and the Notsew Orm Sands Foundation.

Clinical effects of durability of immunosuppression in virologically suppressed ART-initiating persons with HIV in Latin America. A retrospective cohort study.

Background: Clinical outcomes are rarely studied in virologically suppressed people living with HIV (PWH) and incomplete CD4 recovery. To explore whether time living with severe immunosuppression predict clinical outcomes better than baseline or time updated CD4, we estimated the association between cumulative percentage of time with CD4 <200 cells/µL during viral suppression (VS) (%tCD4<200), and mortality and comorbidities during 2000-2019. Methods: In a retrospective cohort analysis, we followed PWH initiating ART in Latin America from first VS (HIV-RNA<200 copies/µL) to death, virological failure or loss to follow-up. We fit Cox models to estimate risk of death and/or AIDS-defining and serious non-AIDS-defining events (ADE and SNADE -cancer, cardiovascular, liver, and renal diseases) by %tCD4<200 (continuous variable). We predicted survival probabilities for each event and calculated risks of hypothetical cases of different %tCD4<200. Findings: In 8,369 patients with 34·9 months of follow-up (median, IQR: 16·7, 69·1), 4,274 (51%) started ART with CD4<200 cells/µL. Median %tCD4<200 was 0% (IQR: 0, 15%). We identified 195 (2·3%) deaths and 584 (7·2%) patients with ADE/SNADE. For an increased %tCD4<200 of 15% (e.g., 15% vs. 0%), the adjusted relative hazard (aHR) of death was 1·27 (95% confidence interval [CI]: 1·19 - 1·35), of ADE/SNADE was 1·13 (95%CI: 1·09 - 1·17), of SNADE was 0·96 (95%CI: 0·89 - 1·02) and of death/ADE/SNADE was 1·11 (95%CI: 1·07 - 1·14). Estimates were similar after adjusting for time updated CD4 count. Interpretation: In virologically suppressed PWH, increased time living with severe immunosuppression had an increased risk of death and ADE/SNADE in this Latin American cohort, independently of time updated CD4 count. Funding: This work was supported by the NIH-funded Caribbean, Central and South America network for HIV epidemiology (CCASAnet, U01AI069923), a member cohort of the International Epidemiologic Databases to Evaluate AIDS (leDEA). This award is funded by the following institutes: Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Cancer Institute (NCI), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Mental Health (NIMH), the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the Fogarty International Center (FIC). Specific funding was provided from the Fogarty International Center (FIC) for lead author, Yanink Caro-Vega, for the Fogarty-IeDEA Mentorship Program (FIMP).

Economic evaluation of strategies for managing women with equivocal cytological results in Brazil.

In Brazil, current management of women with screening results of atypical squamous cells of undetermined significance (ASC-US) is to offer repeat testing at 6-month intervals. Alternative management strategies that have been adopted in many high-income settings are to offer immediate colposcopy referral or to utilise human papillomavirus (HPV) DNA testing as a triage for colposcopy referral, and to consider different strategies according to women's age. The objective of our study was to evaluate the lifetime cost effectiveness in terms of cost per years of life saved (YLS) of these alternative strategies for a middle income setting. A Markov model was developed using data from the Ludwig-McGill cohort and calibrated to independent observational datasets and local cost estimates obtained. In the base-case analysis, repeat cytology was the least costly strategy but also the least effective. Based on the WHO threshold for very cost-effective interventions, HPV triage for women above 30 years-old was the strategy with the highest probability of being cost effective. HPV triage including younger women with ASCUS results would also be a cost-effective option. Whilst there was a slight further gain in effectiveness with immediate colposcopy referral, it was also more expensive and did not appear to be cost effective. Threshold analysis indicated that an HPV test would have to be more than twice as expensive as a cytology test for HPV triage to no longer be cost effective. In conclusion, our results indicate that in middle income settings HPV triage is likely to be the optimal strategy for managing women presenting with ASC-US results.

Potential impact of a presumed increase in the biting activity of dengue-virus-infected Aedes aegypti (Diptera: Culicidae) females on virus transmission dynamics.

Recently, we showed that infection with dengue virus increases the locomotor activity of Aedes aegypti females. We speculate that the observed increased locomotor activity could potentially increase the chances of finding a suitable host and, as a consequence, the relative biting rate of infected mosquitoes. We used a mathematical model to investigate the impact of the increased locomotor activity by assuming that this activity translated into an increased biting rate for infected mosquitoes. The results show that the increased biting rate resulted in dengue outbreaks with greater numbers of primary and secondary infections and with more severe biennial epidemics.

Factors associated with self-reported adherence to daily oral pre-exposure prophylaxis among men who have sex with man and transgender women: PrEP Brasil study.

Understanding the factors associated with pre-exposure prophylaxis (PrEP) adherence may help in the development of strategies to support, motivate and sustain PrEP use. This study estimated self-reported adherence, described perceived barriers and facilitators and investigated factors associated with adherence to daily oral PrEP among men who have sex with man (MSM) and transgender women after 1 year of PrEP use in Brazil. PrEP Brasil was a prospective, multicentre, open-label demonstration study with MSM and transgender women at high risk for HIV infection. We used logistic regression to evaluate factors associated with complete adherence (not forgetting to take any pills in the past 30 days) at week 48. Of 338 participants included in this analysis, 60% reported complete adherence to daily oral PrEP at week 48. Perceived barriers and facilitators to daily oral PrEP were reported by 38.2% and 98.5%, respectively. The most reported barrier and facilitator were 'I forgot to take my pills' (19.2%) and 'Associate PrEP with a daily activity/task' (58.6%), respectively. In final multivariable analysis, living in Rio de Janeiro (aOR: 0.38; 95% CI: 0.20-0.73), being transgender women (aOR: 0.22; 95% CI: 0.07-0.73), reporting stimulant use (a OR: 0.40; 95% CI: 0.20-0.80) and having any perceived barriers to daily oral PrEP (aOR: 0.12; 95% CI: 0.07-0.23) were associated with decreased odds of complete adherence. Our findings provide information for developing the best practices to promote PrEP adherence in the Brazilian context.

Prevalence and factors associated with suicidal behavior among trans women in Rio de Janeiro, Brazil.

BACKGROUND: Trans women face disproportionate burden of adverse health outcomes, including mental health issues. Very little is known about suicidal behavior among trans women in low- and middle-income settings, such as Brazil. We aimed to estimate the prevalence of lifetime suicidal behavior and to identify its associated factors among Brazilian trans women. METHODS: This was a cross-sectional study conducted among 345 trans women living in Rio de Janeiro, Brazil. We examined the prevalence of suicidal behavior (ideation and suicide attempt) and its associated factors using stepwise backward Poisson regression analysis with robust variance. RESULTS: Suicidal ideation was present among 47.25% of participants, and the prevalence of lifetime suicide attempt was 27.25%. Trans women with prior physical violence perpetrated by a family member had significantly higher prevalence of suicidal ideation (adjusted prevalence ratios [aPR]1.37), whereas those who reported sex work had lower prevalence ratio of suicidal ideation (aPR 0.76). Suicide attempt was significantly associated with living alone (aPR 1.48), physical violence by a casual partner (aPR 1.92), and sexual violence by a family member (aPR 1.69). Depression was significantly associated with both outcomes (aPR 1.90 for suicidal ideation and aPR 2.21 for suicide attempt). CONCLUSION: Suicidal behavior prevalence rates among Brazilian trans women were alarming and directly linked to violence and poor mental health. Effective mental health and public health policies addressing violence against trans women are urgently needed to prevent suicidal behavior among this highly vulnerable population.

Preferences for pre-exposure prophylaxis (PrEP) among men who have sex with men and transgender women at risk of HIV infection: a multicentre protocol for a discrete choice experiment in Brazil.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is an important and well-established prevention strategy for sexual acquisition of HIV. In Brazil, transgender women (TGW) and men who have sex with men (MSM) bear the largest burden among key populations. Little is known about preferences for PrEP characteristics in these vulnerable populations in Latin America. The goal of this study is to investigate preferences of TGW and MSM with respect to PrEP characteristics, whether current user or not, and to assess any attributes and levels that may improve the decision to start using PrEP (uptake) and optimal continuity of use (adherence), which are important dimensions for PrEP success. METHODS AND ANALYSIS: We hereby outline the protocol of a discrete choice experiment (DCE) to be conducted among TGW and MSM in Brazil. The study will be carried out in two phases. The first phase involves literature review and qualitative approaches including in-depth interviews to inform the development of the DCE (attributes and levels). The second phase entails the DCE survey and supporting questions pertaining to sociodemographic and risk behaviour information. The survey is aimed at current PrEP users and non-users, consisting of two modes of administration: face to face in five Brazilian capitals (Rio de Janeiro, Brasília, Manaus, Porto Alegre and Salvador) and online targeting the entire country. A D-efficient zero-prior blocked experimental design will be used to select 60 paired-profile DCE choice tasks, in which participants will be randomly assigned to one of four groups and presented with a set of 15 choice tasks. The planned sample size is 1000 volunteers. ETHICS, TIMELINE AND DISSEMINATION: The study was approved by Comitê de Ética em Pesquisa-Instituto Nacional de Infectologia Evandro Chagas-INI/FIOCRUZ, CEP/INI, CAAE 28416220.2.1001.5262, approval number 3.979.759 in accordance with the Comissão Nacional de Ética em Pesquisa (CONEP-Brazilian National Board of Research Ethics). The study will be conducted between 2020 and 2021. The results will be disseminated to the scientific community and to the public in general through publications in published in peer-reviewed journals and in scientific conferences.

How heuristics and cognitive biases affect vaccination decisions.

Immunization, the most successful public health intervention to date, can only be effective if eligible individuals or their legal representatives have access to vaccines and subsequently comply with their use. Under-vaccination stems from multiple causes: access, affordability, awareness, acceptance and activation. In this paper, we focus on acceptance and, specifically, on factors pertaining to individual or parental compliance, specifically the psychology of judgment and decision making. We describe how heuristics and cognitive biases - a facet of thoughts and feelings - affect vaccination decision making. Additionally, we address when and how social processes play a role and how attitudes towards vaccines might reflect a more general underlying attitude or ideology. The understanding of how decision making, with regards to vaccines occurs, and the role played by heuristics and cognitive biases can help inform more appropriate public health interventions.

Human papillomavirus (HPV) vaccination coverage in Brazil: spatial and age cohort heterogeneity. / Cobertura da vacina papilomavírus humano (HPV) no Brasil: heterogeneidade espacial e entre coortes etárias.

OBJECTIVE: To estimate the coverage of the first and second dose of the human papillomavirus (HPV) vaccine in Brazil according to microregion, comparing cohorts of girls aged 14, 15, and 16 years in 2017, and investigate the association between spatial heterogeneity in vaccination coverage and sociodemographic variables. METHODS: Information about the doses administered from 2013 to 2017 by age was gathered from the National Immunization Program. The number of girls aged seven, eight, and nine years living in each microregion in 2010 was obtained from the 2010 Brazilian Census. For the analysis, the cumulated vaccination coverage per microregion (n = 558) was categorized as low (< 80%) and adequate (≥ 80%), and a random intercept logistic model was adjusted, with adequate vaccination coverage as the outcome. The random effect (federative unit) was included to identify the correlation between microregions that belong to the same state. RESULTS: The percentage of microregions with adequate vaccination coverage was significantly higher in the first dose (between 91.8 and 159.2%), regardless of the cohort. The coverage of the second dose was lower (between 7 and 79.9%), with heterogeneity associated with the degree of urbanization and households with private bathrooms in the municipality. The random effect showed a strong explanatory power, suggesting important differences among Brazilian states as to the outreach of vaccination coverage. CONCLUSION: Although the HPV vaccine is available through the Immunization Program, the findings of the present study point to a difficulty in achieving adequate vaccination coverage.

OBJETIVO: Estimar a cobertura da primeira e da segunda dose da vacina papilomavírus humano (HPV) no Brasil, conforme a microrregião, comparando-se as coortes de meninas com 14, 15 e 16 anos em 2017, e investigar a associação da heterogeneidade espacial na cobertura vacinal com variáveis sociodemográficas. MÉTODOS: A informação sobre doses aplicadas nos anos de 2013 a 2017 por idade foi obtida do Programa Nacional de Imunizações. O número de meninas residentes com sete, oito e nove anos em 2010, em cada microrregião, é oriundo do censo brasileiro de 2010. Para a análise, a cobertura vacinal acumulada por microrregião (n = 558) foi categorizada em baixa (< 80%) e adequada (≥ 80%), e um modelo logístico com intercepto aleatório foi ajustado, tendo cobertura vacinal adequada como desfecho. O efeito aleatório (unidade da federação) foi incluído para captar a correlação entre microrregiões que pertencem ao mesmo estado. RESULTADOS: O percentual de microrregiões que alcançou a cobertura vacinal adequada foi significativamente maior para a primeira dose (entre 91,8 e 159,2%), independentemente da coorte. Observou-se menor cobertura da segunda dose (entre 7 e 79,9%), com heterogeneidade associada ao grau de urbanização e à presença de domicílios com banheiro de uso próprio no município. O efeito aleatório mostrou forte poder explicativo, sugerindo importantes diferenças entre os estados brasileiros no alcance da cobertura vacinal. CONCLUSÃO: Apesar de a vacina HPV estar disponível no Programa de Imunização, os achados do presente estudo apontam para uma dificuldade do alcance da cobertura vacinal adequada.

Predictors of influenza vaccine uptake: translation into Portuguese and validation of a questionnaire. / Preditores de aceitação da vacina contra influenza: tradução para o português e validação de um questionário.

The difficulty in achieving ideal coverage rates with the influenza vaccine in Brazil and the growing wave of antivaccine movements in the world point to the need for a more in-depth understanding of the individual determinants of to this vaccine uptake. The Health Belief Model, a theoretical model that aims to explain and predict health-related behaviors, suggests that individual beliefs influence the adoption of health-related behaviors. The objective of this study was a cross-cultural adaptation of an instrument to assess predictors of influenza vaccine uptake in Brazilian adults. The authors conducted translation, back-translation, face validity, and a survey for construct validity. They also analyzed the factors associated with influenza vaccine uptake in 2017. An instrument originally with seven domains was identified and selected. In the factor analysis, four of the model's seven constructs were validated: Susceptibility, Barriers, Cues to action, and Self-efficacy. In the survey with 396 persons, 59.3% reported having received the influenza vaccine in the last campaign in 2017. Female sex, age > 50 years, pregnancy, vaccination in private healthcare services, hepatitis B vaccination, and influenza vaccination prior to 2017 were associated with vaccination in 2017. In the final logistic regression model, perceived Barriers appeared as a strong factor for non-vaccination, while Cues to action increased the odds of vaccination.

A dificuldade de alcançar coberturas ideais para a vacina contra influenza no Brasil e a crescente onda do movimento antivacina no mundo apontam a necessidade de aprofundar a compreensão dos determinantes individuais de adesão a essa vacina. O Modelo de Crenças em Saúde, um modelo teórico que objetiva explicar e predizer o comportamento em relação à saúde, sugere que crenças individuais influenciam a adoção de comportamentos relacionados a essa área. Este trabalho teve como objetivo a adaptação transcultural de um instrumento para avaliar os preditores de aceitação da vacina da influenza em adultos no Brasil. Realizaram-se a tradução, a retrotradução, a validade de face e um inquérito para validade de construto. Também foram analisados os fatores associados à adesão à vacina da influenza em 2017. Um instrumento, originalmente com sete domínios, foi identificado e selecionado. Na análise fatorial, quatro dos sete construtos do modelo teórico foram validados: Suscetibilidade, Barreiras, Estímulos para a ação e Motivação para a saúde. No inquérito das 396 pessoas, 59,3% relataram vacinação contra influenza na última campanha de 2017. Sexo feminino, idade > 50 anos, gestante, vacina na rede privada, vacinação contra a hepatite B e influenza antes de 2017 mostraram-se como fatores associados à vacinação em 2017. No modelo logístico final, a percepção de Barreiras apresentou-se como um forte Estímulo para não vacinação, ao passo que Estímulos para a ação atuou aumentando a chance de vacinação.

La dificultad de alcanzar coberturas ideales para la vacuna contra la gripe en Brasil y la creciente ola del movimiento antivacunas en el mundo apunta la necesidad de profundizar la comprensión de los determinantes individuales de adhesión a esa vacuna. El Modelo de Creencias en Salud, un modelo teórico que tiene como objetivo explicar y predecir el comportamiento en relación con la salud, sugiere que las creencias individuales influencian la adopción de comportamientos relacionados con esa área. El objetivo de este trabajo es la adaptación transcultural de un instrumento para evaluar los predictores de aceptación de la vacuna de la gripe en adultos en Brasil. Se realizó la traducción, retrotraducción, validez de la presentación, así como una encuesta para la validez del constructo. También se analizaron los factores asociados con la adhesión a la vacuna de la gripe en 2017. Un instrumento, originalmente con siete dominios, fue identificado y seleccionado. En el análisis factorial, cuatro de los siete constructos del modelo teórico fueron evaluados: Susceptibilidad, Barreras, Estímulos para la acción y Motivación para la salud. En el cuestionario a las 396 personas, 59,3% informaron haber sido vacunadas contra la gripe en la última campaña de 2017. Sexo femenino, edad > 50 años, embarazada, vacunada en la red privada, vacunación contra la hepatitis B y gripe antes de 2017 se mostraron como factores asociados a la vacunación en 2017. En el modelo logístico final, la percepción de Barreras se presentó como un fuerte Estímulo para la no vacunación, al paso que Estímulos para la acción actuó aumentando la oportunidad de vacunación.

Transcendendo: A Cohort Study of HIV-Infected and Uninfected Transgender Women in Rio de Janeiro, Brazil.

Purpose: Worldwide, the burden of adverse health conditions is substantial among travestis and transgender women (trans women). Transcendendo, the first trans-specific cohort in a low- or middle-income country, is an open cohort established in August 2015 to longitudinally evaluate the health aspects of trans women aged ≥18 years in Rio de Janeiro, Brazil. Methods: Study visits occur on an annual basis. Data on sociodemographics, behavioral, gender transition, affirmation procedures, hormone use, discrimination, violence, clinical and mental health, HIV prevention, and care (for those HIV-infected) are collected. Physical examination, anthropometric measurements, and laboratory tests are performed. Results: As of July 2017, 322 trans women were enrolled in the cohort with a median age of 31.5 years (interquartile range 25.7-39.5), of whom 174 (54%) were HIV-infected. The Transcendendo baseline information reinforces the scenario of marginalization and deprivation surrounding trans women. Most participants had low income (62.0% were living with below US$ 10.00/day), showed a very high engagement in sex work (78.6%), and reported increased occurrence of sexual (46.3%) and physical (54.0%) violence. Pre-exposure peophylaxis (PReP) was used by 18.8% of the HIV-uninfected trans women, only through research participation. Positive screening for depression (57.8%) and problematic use of tobacco (56.6%), cannabis (28.9%), cocaine (23.8%), and alcohol (21.5%) were high. Almost all participants (94.8%) reported hormone use at some point, mostly without medical supervision (78.7%). Conclusion: Our results describe a context of exclusion experienced by trans women, exposing vulnerabilities of this population in a middle-income country, with poor access to trans-specific care, HIV prevention and care, and mental health care. Addressing transgender experiences and needs can help the development of strategies to diminish stigma, improve health care environment, guide future research on trans morbidities, substance use, and trans-specific interventions to support health-related recommendations. Ultimately, it contributes to close the gaps concerning transgender health and reinforces that trans care cannot be disentangled from the social environment that surrounds trans women.