Dolutegravir and pregnancy outcomes in women on antiretroviral therapy in Brazil: a retrospective national cohort study.

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.

An Internet-Based HIV Self-Testing Program to Increase HIV Testing Uptake Among Men Who Have Sex With Men in Brazil: Descriptive Cross-Sectional Analysis.

BACKGROUND: Approximately 30% of people living with HIV worldwide are estimated to be unaware of their infection. HIV self-testing (HIVST) is a strategy recommended by the World Health Organization to increase access to and uptake of testing among key populations who are at high risk for HIV infection. OBJECTIVE: This study aimed to describe the development and feasibility of a free, anonymous, internet-based HIVST strategy designed for men who have sex with men in Curitiba, Brazil (electronic testing [e-testing]). METHODS: The project was developed under the scope of the "A Hora é Agora" (The Time is Now) program. Individuals aiming to request an HIVST package (two tests each) answered an anonymous 5-minute questionnaire regarding inclusion criteria and sexual risk behavior. Eligible individuals could receive one package every 6 months for free. Website analytics, response to online questionnaires, package distribution, and return of test results were monitored via a platform-integrated system. RESULTS: Between February 2015 and January 2016, the website documented 17,786 unique visitors and 3218 completed online questionnaires. Most individuals self-reported being white (77.0%), young (median age: 25 years, interquartile range: 22-31 years), educated (87.3% completed secondary education or more), and previously tested for HIV (62.5%). Overall, 2526 HIVST packages were delivered; of those, 542 (21.4%) reported a result online or by mail (23 reactive and 11 invalid). During the study period, 37 individuals who reported using e-testing visited the prespecified health facility for confirmatory testing (30 positive, 7 negative). CONCLUSIONS: E-testing proved highly feasible and acceptable in this study, thus supporting scale-up to additional centers for men who have sex with men in Brazil.

The Brazilian experience of implementing the active pharmacovigilance of dolutegravir.

In 2017, the Ministry of Health Brazilian started using dolutegravir (DTG) 50 mg to all people living with HIV who began antiretroviral therapy (ART) or rescue regimens. Although DTG is thought to have better tolerability levels and a lower possibility of causing adverse reactions, it is necessary to continuously evaluate the safety profile of the drug in the population. Therefore, an active pharmacovigilance project for DTG was implemented. The objective of this study was to describe the Brazilian experience of implementing pharmacovigilance and the results obtained during the period between April and December 2017.Active pharmacovigilance was implemented through patient interviews and an online questionnaire developed in the Medication Logistics Control System (SICLOM).Of the total number of people on DTG in Brazil (79,742) 90.33% participated in the project, and 2.24% of those who participated reported adverse reactions to the drug; of those who reported adverse reactions, 73.86% were on first-line ART regimens, and 26.13% were on third-line regimens. The mean age of the patients who had adverse reactions to DTG was 39 years; 68.79% were male, and 31.21% were female. Of the adverse reactions reported, 50.39% were considered persistent. The 3 most frequent reactions were nausea (13.34%), diarrhea (9.83%), and headaches (9.23%).The Brazilian experience with this project has been deemed successful by federal and local managers, and the online tool to collect data has proved to be an important strategy for the pharmacovigilance of DTG as well as that of other drugs.

The Brazilian comprehensive response to hepatitis C: from strategic thinking to access to interferon-free therapy.

BACKGROUND: Hepatitis C affects over 185 million people around the world. This silent disease is responsible for up to 700,000 deaths per year. Despite the scientific revolution in diagnosis and treatment, hepatitis C control remains a huge challenge due to the cost of effective medications. In response to the global outcry of hepatitis epidemic and the need to improve the nation's public health response, the Ministry of Health of Brazil revolutionized hepatitis C treatment by incorporating highly effective drugs that can be accessed through sustainable and universal means. DISCUSSION: This paper describes the unique process of implementing evidence-informed policy to respond to hepatitis C epidemic through the update of hepatitis C treatment in Brazil based on the estimate of disease prevalence, current international guidelines, and the cost-effectiveness impact in the Brazilian Unified Health System. Through a debate of an experience report, the authors underlie the strategic plan implemented according to the situation analysis that emphasized the need to improve its current response over a relatively short-term period. The comprehensive response is detailed comprising three main objectives: improve treatment outcomes by evaluating and incorporating new and effective medications at a sustainable price; elaborate on clinical guidelines to treat hepatitis C patients; and develop awareness and diagnosis campaigns targeted at the population of interest. In this scenario, Brazil was able to obtain an unprecedented discount for a high-medium income country; provided treatment to more than 7000 individuals in the last 2 months of 2015; and expects to treat 38,000 new patients in 2016. The remarkable process applied in Brazil was developed according to epidemiological data and scientific evidence, and it was motivated by the engagement of the country in the Sustainable Development Goals, which may inspire other developing countries to identify ways to achieve these goals by 2030.

The Men Who Have Sex with Men HIV Care Cascade in Rio de Janeiro, Brazil.

Brazil has a concentrated HIV epidemic and men who have sex with men (MSM) are disproportionately affected. Yet, no data is available on the HIV care cascade for this population. This study aimed to assess the HIV care cascade among MSM newly diagnosed through innovative testing strategies in Rio de Janeiro. Data from 793 MSM and travestites/transgender women (transwomen) tested for HIV at a non-governmental LGBT organization and a mobile testing unit located at a gay friendly venue were analyzed. A 12-month-after-HIV-diagnosis-censored cohort was established using CD4, viral load and combination antiretroviral therapy (cART) longitudinal data from those diagnosed with HIV. A cross-sectional HIV care cascade was built using this data. The relative risks of achieving each cascade-stage were estimated using generalized linear models according to age, self-declared skin-color, education, history of sexually transmitted diseases (STD), drug use and prior HIV testing. From Jan-2013 to Jan-2014, 793 MSM and transwomen were tested, 131 (16.5%) were HIV-infected. As of January 2015, 95 (72.5%) were linked to HIV care, 90 (68.7%) were retained in HIV care, 80 (61.1%) were on cART, and 50 (38.2%) were virally suppressed one year after HIV diagnosis. Being non-white (Relative risk [lower bound; upper bound of 95% confidence interval] = 1.709 [1.145; 2.549]) and having a prior HIV-test (1.954 [1.278; 2.986]) were associated with an HIV-positive diagnosis. A higher linkage (2.603 [1.091; 6.211]) and retention in care (4.510 [1.880; 10.822]) were observed among those who were older than 30 years of age. Using community-based testing strategies, we were able to access a high-risk MSM population and a small sample of transwomen. Despite universal care coverage and the test-and-treat policy adopted in Brazil, the MSM cascade of care indicates that strategies to increase linkage to care and prompt cART initiation targeted to these populations are critically needed. Interventions targeting non-white and young MSM should be prioritized.