Prevalence and predictors of anti-SARS-CoV-2 serology in a highly vulnerable population of Rio de Janeiro: A population-based serosurvey.

Background: COVID-19 serosurveys allow for the monitoring of the level of SARS-CoV-2 transmission and support data-driven decisions. We estimated the seroprevalence of anti-SARS-CoV-2 antibodies in a large favela complex in Rio de Janeiro, Brazil. Methods: A population-based panel study was conducted in Complexo de Manguinhos (16 favelas) with a probabilistic sampling of participants aged ≥1 year who were randomly selected from a census of individuals registered in primary health care clinics that serve the area. Participants answered a structured interview and provided blood samples for serology. Multilevel regression models (with random intercepts to account for participants' favela of residence) were used to assess factors associated with having anti-S IgG antibodies. Secondary analyses estimated seroprevalence using an additional anti-N IgG assay. Findings: 4,033 participants were included (from Sep/2020 to Feb/2021, 22 epidemic weeks), the median age was 39·8 years (IQR:21·8-57·7), 61% were female, 41% were mixed-race (Pardo) and 23% Black. Overall prevalence was 49·0% (95%CI:46·8%-51·2%) which varied across favelas (from 68·3% to 31·4%). Lower prevalence estimates were found when using the anti-N IgG assay. Odds of having anti-S IgG antibodies were highest for young adults, and those reporting larger household size, poor adherence to social distancing and use of public transportation. Interpretation: We found a significantly higher prevalence of anti-S IgG antibodies than initially anticipated. Disparities in estimates obtained using different serological assays highlight the need for cautious interpretation of serosurveys estimates given the heterogeneity of exposure in communities, loss of immunological biomarkers, serological antigen target, and variant-specific test affinity. Funding: Fundação Oswaldo Cruz, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), the European Union's Horizon 2020 research and innovation programme, Royal Society, Serrapilheira Institute, and FAPESP.

Development and Evaluation of Short-Form Measures of the HIV/AIDS Knowledge Assessment Tool Among Sexual and Gender Minorities in Brazil: Cross-sectional Study.

BACKGROUND: In theoretical models of health behavior, knowledge about disease transmission and self-protective behaviors are conceptualized as important drivers of behavior change. Several studies conducted in Brazil point to an unfortunate convergence of sexual and gender minority (SGM) populations with low levels of HIV knowledge and younger age, lower education, engagement in higher-risk sexual behavior, and never having tested for HIV. Measures to assess level of HIV knowledge have been previously published, including the 12-item HIV/AIDS Knowledge Assessment (HIV-KA) tool. However, measure length can be a barrier to assessment. OBJECTIVE: We started from the 12-item HIV-KA tool and developed candidate short forms using statistical procedures, evaluated their psychometric properties, and tested the equivalency of their associations with other measures of HIV knowledge compared to the 12-item version. METHODS: A convenience sample of SGM was recruited during September 2020 to complete an online survey through advertisements on two social networking apps (Grindr and Hornet). The survey instrument included items on sociodemographic information, prior HIV testing and HIV test results, preexposure prophylaxis (PrEP) and antiretroviral treatment use, sexual behavior, and 3 HIV knowledge measures: the HIV-KA, World Health Organization Knowledge About HIV Transmission Prevention Indicator, and the Brief HIV Knowledge Questionnaire. We used exploratory factor analysis and confirmatory factor analysis (CFA) to assess the factor structure of the of the HIV-KA. We used optimal test assembly (OTA) methods to develop candidate short forms of the HIV-KA and evaluated them based on prespecified reliability, concurrent validity, and statistically equivalent convergent validity criteria. RESULTS: Among 2552 SGM individuals from Brazil, mean age was 35.1 years, 98.2% (2507/2552) cisgender men and 1.8% (45/2552) transgender/nonbinary, 56.5% (1441/2552) White, and 31.0% (792/2552) self-reported HIV positive. CFA indicated a 1-factor structure for the 12-item HIV-KA. Concurrent validity correlations were high for all short forms with 6 items, but only versions with 9 items were as reliable as the full-length form and demonstrated equivalency for convergent validity correlations. Suggesting post hoc convergent validity, HIV knowledge scores using the 9- and 10-item short forms were higher for participants who perceived the Undetectable Equals Untransmittable (U=U) slogan as completely accurate versus not accurate. Suggesting post hoc concurrent validity, participants of younger age, of Black, Pardo or indigenous race, and reporting lower education and lower income scored lower on HIV knowledge. Participants who never tested for HIV scored lower than those who tested negative or positive, while those currently using PrEP scored higher than those reporting past or never use. CONCLUSIONS: OTA methods were used to shorten the 12-item HIV-KA to 9-item and 10-item versions while maintaining comparable reliability and validity among a large sample of Brazilian SGM. However, these short forms did not shorten sufficiently to justify deviation from the full measure.

Late initiation of antiretroviral therapy: inequalities by educational level despite universal access to care and treatment.

BACKGROUND: Late antiretroviral treatment initiation for HIV disease worsens health outcomes and contributes to ongoing transmission. We investigated whether socioeconomic inequalities exist in access to treatment in a setting with universal access to care and treatment. METHODS: This study investigated the association of educational level, used as a proxy for socioeconomic status, with late treatment initiation and treatment initiation with advanced disease. Study participants included adults (≥25 years) who started treatment from 2005 to 2018 at Instituto Nacional de Infectologia Evandro Chagas of Fundação Oswaldo Cruz (INI/FIOCRUZ), Rio de Janeiro, Brazil. Educational level was categorized following UNESCO's International Standard Classification of Education: incomplete basic education, basic education, secondary level, and tertiary level. We defined late treatment initiation as those initiating treatment with a CD4 < 350 cells/mL or an AIDS-defining event, and treatment initiation with advanced disease as those initiating treatment with a CD4 < 200 cells/mL or an AIDS-defining event. A directed acyclic graph (DAG) was constructed to represent the theoretical-operational model and to understand the involvement of covariates. Logistic regression models were used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). Multiple imputation using a chained equations approach was used to treat missing values and non-linear terms for continuous variables were tested. RESULTS: In total, 3226 individuals composed the study population: 876 (27.4%) had incomplete basic education, 540 (16.9%) basic, 1251 (39.2%) secondary level, and 525 (16.4%) tertiary level. Late treatment initiation was observed for 2076 (64.4%) while treatment initiation with advanced disease was observed for 1423 (44.1%). Compared to tertiary level of education, incomplete basic, basic and secondary level increased the odds of late treatment initiation by 89% (aOR:1.89 95%CI:1.47-2.43), 61% (aOR:1.61 95%CI:1.23-2.10), and 35% (aOR:1.35 95%CI:1.09-1.67). Likewise, the odds of treatment initiation with advanced disease was 2.5-fold (aOR:2.53 95%CI:1.97-3.26), 2-fold (aOR:2.07 95%CI:1.59-2.71), 1.5-fold (aOR:1.51 95%CI:1.21-1.88) higher for those with incomplete basic, basic and secondary level education compared to tertiary level. CONCLUSION: Despite universal access to HIV care and antiretroviral treatment, late treatment initiation and social inequalities persist. Lower educational level significantly increased the odds of both outcomes, reinforcing the existence of barriers to "universal" antiretroviral treatment.

Modeling the cost-effectiveness of maternal acellular pertussis immunization (aP) in different socioeconomic settings: A dynamic transmission model of pertussis in three Brazilian states.

OBJECTIVES: Using dynamic transmission models we evaluated the health and cost outcomes of adding acellular pertussis (aP) vaccination of pregnant women to infant vaccination in three Brazilian states that represent different socioeconomic conditions. The primary objective was to determine whether the same model structure could be used to represent pertussis disease dynamics in differing socioeconomic conditions. METHODS: We tested three model structures (SIR, SIRS, SIRSIs) to represent population-level transmission in three socio-demographically distinct Brazilian states: São Paulo, Paraná and Bahia. Two strategies were evaluated: infant wP vaccination alone versus maternal aP immunization plus infant wP vaccination. Model projections for 2014-2029 include outpatient and inpatient pertussis cases, pertussis deaths, years of life lost, disability-adjusted life-years (DALYs) lost, and costs (in 2014 USD) of maternal aP vaccination, infant vaccination, and pertussis medical treatment. Incremental cost per DALY averted is presented from the perspective of the Brazilian National Health System. RESULTS: Based on goodness-of-fit statistics, the SIRSIs model fit best, although it had only a modest improvement in statistical quantitative assessments relative to the SIRS model. For all three Brazilian states, maternal aP immunization led to higher costs but also saved infant lives and averted DALYs. The 2014 USD cost/DALY averted was $3068 in Sao Paulo, $2962 in Parana, and $2022 in Bahia. These results were robust in sensitivity analyses with the incremental cost-effectiveness ratios exceeding per capita gross regional product only when the probability that a pertussis case is reported was assumed higher than base case implying more overt cases and deaths and therefore more medical costs. CONCLUSIONS: The same model structure fit all three states best, supporting the idea that the disease behaves similarly across different socioeconomic conditions. We also found that immunization of pregnant women with aP is cost-effective in diverse Brazilian states.

Health-related quality of life assessment among people living with HIV in Rio de Janeiro, Brazil: a cross-sectional study.

PURPOSE: To assess health-related quality of life (HRQoL) and its associated factors among people living with HIV/AIDS (PLWHA) in Rio de Janeiro, Brazil. METHODS: A cross-sectional study including PLWHA receiving usual HIV-care at Instituto Nacional de Infectologia Evandro Chagas (INI/Fiocruz) was conducted between 2014 and 2016 in Rio de Janeiro, Brazil. The EQ-5D-3L assessed HRQoL; PHQ-2 and ASSIST were used for screening depression and substance use, respectively. Clinical variables were obtained from the INI/Fiocruz cohort database, and structured questions evaluated intimate partner violence, sexual abstinence and relationship status. Data were analysed using multivariable Tobit regression model. RESULTS: A total of 1480 PLWHA were included: 64.7% were male at birth (38.4% men who have sex with men [MSM], 24.3% heterosexual men and 2% transgender women [TGW]); median age was 43.1 years, and 95.8% were receiving antiretroviral therapy. The median EQ-5D-3L utility score was 0.801. Results showed that the following factors: MSM and women; older age; lower educational level; no engagement in a relationship; depression screening positive; polysubstance use; and, detectable viral load were independently associated with worse HRQoL. CONCLUSIONS: PLWHA under care at INI/Fiocruz presented good HRQoL. Polysubstance use, depression and lower educational level were among the factors negatively associated with HRQoL. This was the first time that the EQ-5D-3L utility scores were calculated for a considerable number of PLWHA in Brazil, which is a fundamental piece of information for future cost-effectiveness analysis.

PrEP adopted by the brazilian national health system: What is the size of the demand?

BACKGROUND: Brazil's response to the HIV epidemic now includes free access to preexposure prophylaxis (PrEP) to populations at substantial risk for HIV infection including men who have sex with men (MSM). We used nationally representative demographic, epidemiologic, and surveillance data to offer estimates for the number of MSM at substantial risk for HIV infection who might be eligible and willing to use PrEP in Brazil. METHODS: Starting from the age/sex-stratified population, we calculated the number of men aged 15 to 64 years, in 5-year age groups, and the proportion of those who report sex with other men during their lifetime. We focused on 11 cities (representing all regions) that are responsible for a significant fraction of the HIV burden of the country and used city-specific HIV prevalence estimates to infer the fraction of MSM who are HIV-negative. We then derived the proportion of HIV-negative MSM under substantial risk for HIV infection defined as having unprotected receptive anal intercourse in the 6 months before study participation. Finally, PrEP uptake among the eligible was inferred from the PrEP Brazil study. RESULTS: Our results show that PrEP demand in these 11 cities is of 66,120 men aged 15 to 64 years. When we consider the lower and upper bounds for the available parameters, we find that PrEP demand in these 11 cities might vary from 33,378 to 97,962 men. If PrEP is restricted to those aged 15 to 49 years, demand drops by 20%. PrEP demand varies considerably by city, mostly because of the differences in population size and city-specific HIV prevalence. DISCUSSION: We have shed light on the probable size of PrEP demand in Brazil certain that the incorporation of PrEP as part of Brazil's combination prevention for populations at substantial risk for HIV infection is a necessary challenge. PrEP will not only prevent HIV infections, it will also expand testing among the most vulnerable with the added benefit of offering combination prevention for the uninfected and immediate treatment for those already infected. As such, expected added benefits of PrEP will be earlier linkage to care, prompt treatment initiation leading to health benefits and decreased transmission.

The cost-effectiveness of HIV pre-exposure prophylaxis in men who have sex with men and transgender women at high risk of HIV infection in Brazil.

INTRODUCTION: Men who have sex with men (MSM) and transgender women (TGW) in Brazil experience high rates of HIV infection. We examined the clinical and economic outcomes of implementing a pre-exposure prophylaxis (PrEP) programme in these populations. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International model of HIV prevention and treatment to evaluate two strategies: the current standard of care (SOC) in Brazil, including universal ART access (No PrEP strategy); and the current SOC plus daily tenofovir/emtracitabine PrEP (PrEP strategy) until age 50. Mean age (31 years, SD 8.4 years), age-stratified annual HIV incidence (age ≤ 40 years: 4.3/100 PY; age > 40 years: 1.0/100 PY), PrEP effectiveness (43% HIV incidence reduction) and PrEP drug costs ($23/month) were from Brazil-based sources. The analysis focused on direct medical costs of HIV care. We measured the comparative value of PrEP in 2015 United States dollars (USD) per year of life saved (YLS). Willingness-to-pay threshold was based on Brazil's annual per capita gross domestic product (GDP; 2015: $8540 USD). RESULTS: Lifetime HIV infection risk among high-risk MSM and TGW was 50.5% with No PrEP and decreased to 40.1% with PrEP. PrEP increased per-person undiscounted (discounted) life expectancy from 36.8 (20.7) years to 41.0 (22.4) years and lifetime discounted HIV-related medical costs from $4100 to $8420, which led to an incremental cost-effectiveness ratio (ICER) of $2530/YLS. PrEP remained cost-effective (<1x GDP) under plausible variation in key parameters, including PrEP effectiveness and cost, initial cohort age and HIV testing frequency on/off PrEP. CONCLUSION: Daily tenofovir/emtracitabine PrEP among MSM and TGW at high risk of HIV infection in Brazil would increase life expectancy and be highly cost-effective.

Retention in Early Care at an HIV Outpatient Clinic in Rio de Janeiro, Brazil, 2000-2013.

Retention in early HIV care has been associated with virologic suppression and improved survival, but remains understudied in Brazil. We estimated retention in early HIV care for the period 2000-2013, and identified socio-demographic and clinical factors associated with good retention in an urban cohort from Rio de Janeiro, Brazil. Antiretroviral therapy-naïve, HIV-infected persons ≥18 years old linked to care between 2000 and 2011 were included. Retention in the first 2 years post-linkage (i.e. early care) was defined by the proportion of 6-month intervals with ≥1 HIV laboratory result. "Good" retention was defined as ≥1 HIV laboratory result recorded in at least three intervals. Overall, 80 % of participants met criteria for good retention and retention significantly improved over the study period. Older age, higher education level and early antiretroviral therapy initiation were associated with good retention. Efforts to improve retention in early care in this population should target younger and less-educated HIV-infected persons.

Cost-effectiveness of genotype testing for primary resistance in Brazil.

OBJECTIVE: HIV genotype-resistance testing can help identify more effective antiretroviral treatment (ART) regimens for patients, substantially increasing the likelihood of viral suppression and immune recovery. We sought to evaluate the cost-effectiveness of genotype-resistance testing before first-line ART initiation in Brazil. DESIGN: We used a previously published microsimulation model of HIV disease (CEPAC-International) and data from Brazil to compare the clinical impact, costs, and cost-effectiveness of initial genotype testing (Genotype) with no initial genotype testing (No genotype). METHODS: Model parameters were derived from the HIV Clinical Cohort at the Evandro Chagas Clinical Research Institute and from published data, using Brazilian sources whenever possible. Baseline patient characteristics included 69% male, mean age of 36 years (SD, 10 years), mean CD4 count of 347 per microliter (SD, 300/µL) at ART initiation, annual ART costs from 2012 US $1400 to US $13,400, genotype test cost of US $230, and primary resistance prevalence of 4.4%. Life expectancy and costs were discounted 3% per year. Genotype was defined as "cost-effective" compared with No Genotype if its incremental cost-effectiveness ratio was less than 3 times the 2012 Brazilian per capita GDP of US $12,300. RESULTS: Compared with No genotype, Genotype increased life expectancy from 18.45 to 18.47 years and reduced lifetime cost from US $45,000 to $44,770; thus, in the base case, Genotype was cost saving. Genotype was cost-effective at primary resistance prevalence as low as 1.4% and remained cost-effective when subsequent-line ART costs decreased to 30% of baseline value. Cost-inefficient results were observed only when simultaneously holding multiple parameters to extremes of their plausible ranges. CONCLUSIONS: Genotype-resistance testing in ART-naive individuals in Brazil will improve survival and decrease costs and should be incorporated into HIV treatment guidelines in Brazil.

Dengue dynamics and vaccine cost-effectiveness in Brazil.

Recent Phase 2b dengue vaccine trials have demonstrated the safety of the vaccine and estimated the vaccine efficacy with further trials underway. In anticipation of vaccine roll-out, cost-effectiveness analysis of potential vaccination policies that quantify the dynamics of disease transmission are fundamental to the optimal allocation of available doses. We developed a dengue transmission and vaccination model and calculated, for a range of vaccination costs and willingness-to-pay thresholds, the level of vaccination coverage necessary to sustain herd-immunity, the price at which vaccination is cost-effective and is cost-saving, and the sensitivity of our results to parameter uncertainty. We compared two vaccine efficacy scenarios, one a more optimistic scenario and another based on the recent lower-than-expected efficacy from the latest clinical trials. We found that herd-immunity may be achieved by vaccinating 82% (95% CI 58-100%) of the population at a vaccine efficacy of 70%. At this efficacy, vaccination may be cost-effective for vaccination costs up to US$ 534 (95% CI $369-1008) per vaccinated individual and cost-saving up to $204 (95% CI $39-678). At the latest clinical trial estimates of an average of 30% vaccine efficacy, vaccination may be cost-effective and cost-saving at costs of up to $237 (95% CI $159-512) and $93 (95% CI $15-368), respectively. Our model provides an assessment of the cost-effectiveness of dengue vaccination in Brazil and incorporates the effect of herd immunity into dengue vaccination cost-effectiveness. Our results demonstrate that at the relatively low vaccine efficacy from the recent Phase 2b dengue vaccine trials, age-targeted vaccination may still be cost-effective provided the total vaccination cost is sufficiently low.