Impact of maternal ART on mother-to-child transmission (MTCT) of HIV at six weeks postpartum in Rwanda

BACKGROUND: In 2010, Rwanda adopted ART for prevention of mother to child transmission of HIV from pregnant women living with HIV during pregnancy and breasfeeding period. This study examines rates of mother-to-childtransmission of HIV at 6–10 weeks postpartum and risk factors for mother-to-child transmission of HIV (MTCT) among HIV infected women on ART during pregnancy and breastfeeding. METHODS: A cross-sectional survey study was conducted between July 2011–June 2012 among HIV-exposed infants aged 6–10 weeks and their mothers/caregivers. Stratified multi-stage, probability proportional to size and systematic sampling to select a national representative sample of clients. Consenting mothers/caregivers were interviewed on demographic and program interventions. Dry blood spots from HIV-exposed infants were collected for HIV testing using DNA PCR technique. Results are weighted for sample realization. Univariable analysis of socio-demographic and programmatic determinants of early mother-to-child transmission of HIV was conducted. Variables were retained for final multivariable models if they were either at least of marginal significance (p-value < 0.10) or played a confounding role (the variable had a noticeable impact > 10% change on the effect estimate). RESULTS: The study sample was 1639 infants with HIV test results. Twenty-six infants were diagnosed HIV-positive translating to a weighted MTCT estimate of 1.58% (95% CI 1.05–2.37%). Coverage of most elimination of MTCT (EMTCT) program interventions, was above 80, and 90.4% of mother-infant pairs received antiretroviral treatment or prophylaxis. Maternal ART and infant antiretroviral prophylaxis (OR 0.01; 95%CI 0.001–0.17) and maternal age older than 25 years were significantly protective (OR 0.33; 95%CI 0.14–0.78). No disclosure of HIV status, not testing for syphilis during pregnancy and preterm birth were significant risk factors for MTCT. Factors suggesting higher sociodemographic status (flush toilet, mother self-employed) were borderline risk factors for MTCT. CONCLUSION: ART for all women during pregnancy and breastfeeding was associated with the estimated low MTCT rate of 1.58%. Mothers who did not receive a full package of anti-retroviral therapy according to the Rwanda EMTCT protocol, and young and single mothers were at higher risk of MTCT and should be targeted for support in preventing HIV infection

Use of interrupted time series methods in the evaluation of health system quality improvement interventions: A methodological systematic review

Background When randomisation is not possible, interrupted time series (ITS) design has increasingly been advocated as a more robust design to evaluating health system quality improvement (QI) interventions given its ability to control for common biases in healthcare QI. However, there is a potential risk of producing misleading results when this rather robust design is not used appropriately. We performed a methodological systematic review of the literature to investigate the extent to which the use of ITS has followed best practice standards and recommendations in the evaluation of QI interventions. Methods We searched multiple databases from inception to June 2018 to identify QI intervention studies that were evaluated using ITS. There was no restriction on date, language and participants. Data were synthesised narratively using appropriate descriptive statistics. The risk of bias for ITS studies was assessed using the Cochrane Effective Practice and Organisation of Care standard criteria. The systematic review protocol was registered in PROSPERO (registration number: CRD42018094427). Results Of 4061 potential studies and 2028 unique records screened for inclusion, 120 eligible studies assessed eight QI strategies and were from 25 countries. Most studies were published since 2010 (86.7), reported data using monthly interval (71.4), used ITS without a control (81) and modelled data using segmented regression (62.5). Autocorrelation was considered in 55 of studies, seasonality in 20.8 and non-stationarity in 8.3. Only 49.2 of studies specified the ITS impact model. The risk of bias was high or very high in 72.5 of included studies and did not change significantly over time. Conclusions The use of ITS in the evaluation of health system QI interventions has increased considerably over the past decade. However, variations in methodological considerations and reporting of ITS in QI remain a concern, warranting a need to develop and reinforce formal reporting guidelines to improve its application in the evaluation of health system QI interventions. © Author(s) 202

A multi-center, adaptive, randomized, platform trial to evaluate the effect of repurposed medicines in outpatients with early coronavirus disease 2019 (COVID-19) and high-risk for complications: the TOGETHER master trial

ABSTRACT Background Although vaccines are currently available for coronavirus disease 2019 (COVID-19), there remains a need for an effective and affordable outpatient treatment for early COVID-19. Multiple repurposed drugs have shown promise in treating COVID-19. We describe a master protocol that will assess the efficacy of different repurposed drugs as treatments for early COVID-19 among outpatients at a high risk for severe complications. Methods The TOGETHER Trial is an international (currently in Brazil), multi-center platform adaptive randomized, placebo-controlled, clinical trial. Patients are included if they are at least 18 years of age, have a positive antigen test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and have an indication for high risk of disease severity, including co-morbidities, older age, or high body mass index. Eligible patients are randomized with equal chance to an investigational product (IP) or to placebo. The primary endpoint is emergency room required observation for more than 6 hours or hospitalization due to clinical worsening of COVID-19; up to 28 days after randomization. Key secondary endpoints include viral clearance, clinical improvement, hospitalization for any cause, mortality for any cause, and safety and tolerability of each IP. Scheduled interim analyses are conducted and reviewed by the Data and Safety Monitoring Committee (DSMC), who make recommendations on continuing or stopping each IP. The platform adaptive design go-no go decision rules are extended to dynamically incorporate external evidence on COVID-19 interventions from ongoing independent randomized clinical trials. Discussion Results from this trial will assist in the identification of therapeutics for COVID-19 that can easily be scaled in low- and middle-income settings. The novel methodological extension of the platform adaptive design to dynamically incorporate external evidence is one of the first of its kind and may provide highly valuable information for all COVID-19 trials going forward

Early Treatment with Pegylated Interferon Lambda for Covid-19

Background: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. Methods: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 μg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. Results: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results: were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. Conclusions: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo

Rwanda 20 years on: investing in life

Two decades ago, the genocide against the Tutsis in Rwanda led to the deaths of 1 million people, and the displacement of millions more. Injury and trauma were followed by the effects of a devastated health system and economy. In the years that followed, a new course set by a new government set into motion equity-oriented national policies focusing on social cohesion and people-centred development. Premature mortality rates have fallen precipitously in recent years, and life expectancy has doubled since the mid-1990s. Here we reflect on the lessons learned in rebuilding Rwanda's health sector during the past two decades, as the country now prepares itself to take on new challenges in health-care delivery