A multinational Delphi consensus to end the COVID-19 public health threat.

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

A pooled testing strategy for identifying SARS-CoV-2 at low prevalence.

Suppressing infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will probably require the rapid identification and isolation of individuals infected with the virus on an ongoing basis. Reverse-transcription polymerase chain reaction (RT-PCR) tests are accurate but costly, which makes the regular testing of every individual expensive. These costs are a challenge for all countries around the world, but particularly for low-to-middle-income countries. Cost reductions can be achieved by pooling (or combining) subsamples and testing them in groups1-7. A balance must be struck between increasing the group size and retaining test sensitivity, as sample dilution increases the likelihood of false-negative test results for individuals with a low viral load in the sampled region at the time of the test8. Similarly, minimizing the number of tests to reduce costs must be balanced against minimizing the time that testing takes, to reduce the spread of the infection. Here we propose an algorithm for pooling subsamples based on the geometry of a hypercube that, at low prevalence, accurately identifies individuals infected with SARS-CoV-2 in a small number of tests and few rounds of testing. We discuss the optimal group size and explain why, given the highly infectious nature of the disease, largely parallel searches are preferred. We report proof-of-concept experiments in which a positive subsample was detected even when diluted 100-fold with negative subsamples (compared with 30-48-fold dilutions described in previous studies9-11). We quantify the loss of sensitivity due to dilution and discuss how it may be mitigated by the frequent re-testing of groups, for example. With the use of these methods, the cost of mass testing could be reduced by a large factor. At low prevalence, the costs decrease in rough proportion to the prevalence. Field trials of our approach are under way in Rwanda and South Africa. The use of group testing on a massive scale to monitor infection rates closely and continually in a population, along with the rapid and effective isolation of people with SARS-CoV-2 infections, provides a promising pathway towards the long-term control of coronavirus disease 2019 (COVID-19).

Monitoring of Adverse Events in Recipients of the 2-Dose Ebola Vaccine Regimen of Ad26.ZEBOV Followed by MVA-BN-Filo in the UMURINZI Ebola Vaccination Campaign.

BACKGROUND: From 2019 to 2021, Rwandan residents of the border with the Democratic Republic of the Congo were offered the Ad26.ZEBOV (adenovirus type 26 vector vaccine encoding Ebola virus glycoprotein) and MVA-BN-Filo (modified vaccinia virus Ankara vector vaccine, encoding glycoproteins from Ebola, Sudan, Marburg, and nucleoprotein from Tai Forest viruses) Ebola vaccine regimen. METHODS: Nonpregnant persons aged ≥2 years were eligible. Unsolicited adverse events (UAEs) were reported through phone calls or visits, and serious adverse events (SAEs) were recorded per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines. RESULTS: Following Ad26.ZEBOV, UAEs were reported by 0.68% of 216 113 vaccinees and were more common in younger children (aged 2-8 years, 1.2%) compared with older children (aged 9-17 years, 0.4%) and adults (aged ≥18 years, 0.7%). Fever and headache were the most reported symptoms. All 17 SAEs related to vaccine were in children aged 2-8 years (10 postvaccination febrile convulsions ± gastroenteritis and 7 fever and/or gastroenteritis). The incidence of febrile seizures was 8 of 26 062 (0.031%) prior to initiation of routine acetaminophen in December 2020 and 2 of 15 897 (0.013%) thereafter. Nonobstetric SAEs were similar in males and females. All 20 deaths were unrelated to vaccination. Young girls and adult women with UAEs were less likely to receive the second dose than those without UAEs. Seven unrelated SAEs occurred in 203 267 MVA-BN-Filo recipients. CONCLUSIONS: Postvaccination febrile convulsions in young children were rare but not previously described after Ad26.ZEBOV and were reduced with routine acetaminophen. The regimen was otherwise safe and well-tolerated.

Engagement in HIV continuum of care: Another step needed to close the gap toward UNAIDS 90-90-90 targets among younger men in Rwanda.

In this study, we measured Rwandan men's engagement in HIV services based on the UNAIDS 90-90-90 targets and assessed factors associated with linkage to HIV services. We analyzed the Rwanda Population-based HIV Impact Assessment (RPHIA) data for 15- to 64-year-old males. We conducted bivariate analysis to assess the distribution and association of sociodemographic characteristics with UNAIDS 90-90-90 targets. We adjusted multivariable models to understand the effect measurement of associated factors and determine the factors that best predict the achievement of UNAIDS 90-90-90. Of 13 780 males aged 15-64 years who participated in the RPHIA and consented to the blood draw and HIV testing, 302 had a positive HIV result, while 301 had valid responses to all variables analyzed in this paper and were included in the analysis. We found that age group was an explanatory and predictive factor for achievement of UNAIDS 90-90-90. Younger men living with HIV (MLHIV) are less likely to have achieved UNAIDS 90-90-90 compared to MLHIV 50-64 years old: adjusted odds ratio (aOR) for MLHIV aged 15-34 years was 0.21 (0.08-0.53) and aOR for MLHIV aged 35-49 years was 0.77 (0.36-1.66). To close the UNAIDS 90-90-90 gap in Rwanda, innovative service delivery strategies are needed to support young MLHIV to reach 90-90-90.

Spatio-temporal dynamic of the COVID-19 epidemic and the impact of imported cases in Rwanda.

INTRODUCTION: Africa was threatened by the coronavirus disease 2019 (COVID-19) due to the limited health care infrastructure. Rwanda has consistently used non-pharmaceutical strategies, such as lockdown, curfew, and enforcement of prevention measures to control the spread of COVID-19. Despite the mitigation measures taken, the country has faced a series of outbreaks in 2020 and 2021. In this paper, we investigate the nature of epidemic phenomena in Rwanda and the impact of imported cases on the spread of COVID-19 using endemic-epidemic spatio-temporal models. Our study provides a framework for understanding the dynamics of the epidemic in Rwanda and monitoring its phenomena to inform public health decision-makers for timely and targeted interventions. RESULTS: The findings provide insights into the effects of lockdown and imported infections in Rwanda's COVID-19 outbreaks. The findings showed that imported infections are dominated by locally transmitted cases. The high incidence was predominant in urban areas and at the borders of Rwanda with its neighboring countries. The inter-district spread of COVID-19 was very limited due to mitigation measures taken in Rwanda. CONCLUSION: The study recommends using evidence-based decisions in the management of epidemics and integrating statistical models in the analytics component of the health information system.

Long-term effect of chronic hepatitis B on mortality in HIV-infected persons in a differential HBV transmission setting.

BACKGROUND: There remain gaps in quantifying mortality risk among individuals co-infected with chronic hepatitis B (HBV) and human immunodeficiency virus (HIV) in sub-Saharan African contexts. Among a cohort of HIV-positive individuals in Rwanda, we estimate the difference in time-to mortality between HBV-positive (HIV/HBV co-infected) and HBV-negative (HIV mono-infected) individuals. METHODS: Using a dataset of HIV-infected adults screened for hepatitis B surface antigen (HBsAg) from January to June 2016 in Rwanda, we performed time-to-event analysis from the date of HBsAg results until death or end of study (31 December 2019). We used the Kaplan-Meier method to estimate probability of survival over time and Cox proportional hazard models to adjust for other factors associated with mortality. RESULTS: Of 21,105 available entries, 18,459 (87.5%) met the inclusion criteria. Mean age was 42.3 years (SD = 11.4) and 394 (2.1%) died during follow-up (mortality rate = 45.7 per 100,000 person-months, 95% confidence interval (CI) 41.4-50.4) Mortality rate ratio for co-infection was 1.7, 95% CI 1.1-2.6, however, Cox regression analysis did not show any association with mortality between compared groups. The adjusted analysis of covariates stratified by co-infection status showed that males, residing outside of the capital Kigali, drinking alcohol, WHO-HIV-clinical stage 3 and 4 were associated with increased mortality in this HIV cohort. CONCLUSIONS: HBV infection does not significantly influence mortality among HIV-infected individuals in Rwanda. The current cohort is likely to have survived a period of high-risk exposure to HBV and HIV mortality and limited health care until their diagnosis.

Cultural adaptation and psychometric evaluation of the Kinyarwanda version of the diabetes-39 (D-39) questionnaire.

BACKGROUND: In recent years, more importance is being given to the assessment of quality of life (QoL) among diabetic patients as a measure of their health and the goal of all health interventions. Other studies have reported a high prevalence of diabetes-related effects on; however, there is a knowledge gap in the region of Sub-Saharan Africa, as is the case for Rwanda, where the prevalence of diabetes is expected to rise over the next decade. The aim of this study is to report on the translation and cultural adaptation of the Diabetes-39 (D-39) questionnaire into the Kinyarwanda and its psychometric properties among diabetic patients in Rwanda. METHODS: The D-39 questionnaire-a five-scale, disease-specific QoL questionnaire-was translated from English to Kinyarwanda, then back-translated to English. A consensus meeting discussed discrepancies and agreed on changes. Interviews were conducted with 26 participants before producing a final version. For the psychometric evaluation, the adapted version was administered to 309 patients with diabetes mellitus. Participants either came from a separate cluster-randomised controlled trial or were recruited ad hoc for this study. The evaluation included testing internal consistency, known group validity, and construct validity. RESULTS: Participants' mean age was 51 ± 12.7 years with a predominance of women (64%) in the sample. All five scales of the questionnaire showed a good internal consistency, with composite reliability of above 0.7. The five-factor model of the questionnaire was fitted to the 39 items. Although the fit was not exact, there was a satisfactory approximate fit (CFI = 0.93, TLI = 0.92, RMSEA = 0.05). There was a good discriminant validity except for the "social burden" and "anxiety and worry" scales (inter-factor correlation = 0.80). CONCLUSIONS: Diabetes-39 is a questionnaire developed in English that was adapted and translated into Kinyarwanda. The Kinyarwanda version of D-39 is a reliable and valid instrument to measure QoL among diabetic patients in Rwanda. The questionnaire can be helpful in research and clinical practice improving health outcomes for patients with diabetes in Rwanda and other Kinyarwanda-competent areas in the sub-region. However, certain cross-cultural differences should be considered.

Leveraging artificial intelligence and data science techniques in harmonizing, sharing, accessing and analyzing SARS-COV-2/COVID-19 data in Rwanda (LAISDAR Project): study design and rationale.

BACKGROUND: Since the outbreak of COVID-19 pandemic in Rwanda, a vast amount of SARS-COV-2/COVID-19-related data have been collected including COVID-19 testing and hospital routine care data. Unfortunately, those data are fragmented in silos with different data structures or formats and cannot be used to improve understanding of the disease, monitor its progress, and generate evidence to guide prevention measures. The objective of this project is to leverage the artificial intelligence (AI) and data science techniques in harmonizing datasets to support Rwandan government needs in monitoring and predicting the COVID-19 burden, including the hospital admissions and overall infection rates. METHODS: The project will gather the existing data including hospital electronic health records (EHRs), the COVID-19 testing data and will link with longitudinal data from community surveys. The open-source tools from Observational Health Data Sciences and Informatics (OHDSI) will be used to harmonize hospital EHRs through the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The project will also leverage other OHDSI tools for data analytics and network integration, as well as R Studio and Python. The network will include up to 15 health facilities in Rwanda, whose EHR data will be harmonized to OMOP CDM. EXPECTED RESULTS: This study will yield a technical infrastructure where the 15 participating hospitals and health centres will have EHR data in OMOP CDM format on a local Mac Mini ("data node"), together with a set of OHDSI open-source tools. A central server, or portal, will contain a data catalogue of participating sites, as well as the OHDSI tools that are used to define and manage distributed studies. The central server will also integrate the information from the national Covid-19 registry, as well as the results of the community surveys. The ultimate project outcome is the dynamic prediction modelling for COVID-19 pandemic in Rwanda. DISCUSSION: The project is the first on the African continent leveraging AI and implementation of an OMOP CDM based federated data network for data harmonization. Such infrastructure is scalable for other pandemics monitoring, outcomes predictions, and tailored response planning.

Effectiveness of Direct-acting Antivirals for the Treatment of Chronic Hepatitis C in Rwanda: A Retrospective Study.

BACKGROUND: Direct-acting antivirals (DAAs) are becoming accessible in sub-Saharan Africa. This study examined the effectiveness of DAAs in patients treated through the Rwandan national health system and identified factors associated with treatment outcomes. METHODS: This retrospective study used data from the national hepatitis C virus (HCV) program for patients who initiated DAAs between November 2015 and March 2017. Sustained virological response at 12 weeks after treatment (SVR12) was the primary outcome. Logistic regression models were fit to estimate the relationship between patients' clinical and demographic characteristics and treatment outcome. RESULTS: 894 patients started treatment during the study period; 590 completed treatment and had SVR12 results. Among the 304 patients without SVR12 results, 48 were lost to follow-up and 256 had no SVR12 results but clinical data indicated they likely completed treatment; these patients were classified as nonvirological failure because viral clearance could not be determined. In a per-protocol analysis of 590 patients with SVR12 results, SVR12 was achieved in 540 (92%), and virological failure occurred in 50 (8%). Pretreatment HCV RNA above the median split was associated with virological failure. Intention-to-treat analyses including all patients showed that SVR12 was achieved in 540 (60%), with nonvirological failure in 304 (34%) and virological failure in 50 (6%). Patients in Western Province were more likely to experience nonvirological failure than patients in Kigali, likely owing to the 5-7-hour travel required to access testing and treatment. CONCLUSIONS: DAAs were effective when implemented through the Rwandan national health system. Decentralization and enhanced financing are underway in Rwanda, which could improve access to treatment and follow-up as the country prepares for HCV elimination.

From Easing Lockdowns to Scaling Up Community-based Coronavirus Disease 2019 Screening, Testing, and Contact Tracing in Africa-Shared Approaches, Innovations, and Challenges to Minimize Morbidity and Mortality.

The arrival of coronavirus disease 2019 (COVID-19) on the African continent resulted in a range of lockdown measures that curtailed the spread of the infection but caused economic hardship. African countries now face difficult choices regarding easing of lockdowns and sustaining effective public health control measures and surveillance. Pandemic control will require efficient community screening, testing, and contact tracing; behavioral change interventions; adequate resources; and well-supported, community-based teams of trained, protected personnel. We discuss COVID-19 control approaches in selected African countries and the need for shared, affordable, innovative methods to overcome challenges and minimize mortality. This crisis presents a unique opportunity to align COVID-19 services with those already in place for human immunodeficiency virus, tuberculosis, malaria, and non communicable diseases through mobilization of Africa's interprofessional healthcare workforce. By addressing the challenges, the detrimental effect of the COVID-19 pandemic on African citizens can be minimized.

Improved quality of life following direct-acting antiviral treatment for chronic hepatitis C infection in Rwanda: Results from a clinical trial in sub-Saharan Africa (the SHARED study).

Around 71 million people are living with chronic hepatitis C virus (HCV) infection, with approximately 14% residing in sub-Saharan Africa. Direct-acting antiviral (DAA) therapies offer clear benefits for liver-related morbidity and mortality, and data from high-income settings suggest that DAA treatments also provide significant benefits in terms of health-related quality of life (HRQL). In this study, we assessed the effect of DAA treatment on HRQL for individuals treated for HCV in a clinical trial in Rwanda. We assessed the HRQL of participants using an 83-question composite survey at Day 0 ('baseline') and Week 24 ('endpoint'). Data were analysed in R. A total of 296 participants were included in this analysis. Their ages ranged from 19 to 90, and 184 (62.2%) were female. There were significant improvements from baseline to endpoint median scores for all physical and mental quality of life sub-scales. Additionally, a reduction-before and after treatment-in the proportion of those classified as depressed and needing social support was statistically significant (both P < .001). Economic productivity increased after treatment (P < .001), and households classified as food secure increased from baseline to endpoint (P < .001). These results demonstrate that Rwandans with chronic HCV infection experience both clinical and HRQL benefits, including household-level benefits like substantial gains in workforce stability, economic productivity, and poverty alleviation, from DAA treatment. A stronger demonstration of accurate and broader household-level benefits achieved through treatment of HCV with DAAs will help financing and investment for HCV in resource-constrained settings become an urgent priority.

Implementation outcomes of national decentralization of integrated outpatient services for severe non-communicable diseases to district hospitals in Rwanda.

OBJECTIVES: Effective coverage of non-communicable disease (NCD) care in sub-Saharan Africa remains low, with the majority of services still largely restricted to central referral centres. Between 2015 and 2017, the Rwandan Ministry of Health implemented a strategy to decentralise outpatient care for severe chronic NCDs, including type 1 diabetes, heart failure and severe hypertension, to rural first-level hospitals. This study describes the facility-level implementation outcomes of this strategy. METHODS: In 2014, the Ministry of Health trained two nurses in each of the country's 42 first-level hospitals to implement and deliver nurse-led, integrated, outpatient NCD clinics, which focused on severe NCDs. Post-intervention evaluation occurred via repeated cross-sectional surveys, informal interviews and routinely collected clinical data over two rounds of visits in 2015 and 2017. Implementation outcomes included fidelity, feasibility and penetration. RESULTS: By 2017, all NCD clinics were staffed by at least one NCD-trained nurse. Among the approximately 27 000 nationally enrolled patients, hypertension was the most common diagnosis (70%), followed by type 2 diabetes (19%), chronic respiratory disease (5%), type 1 diabetes (4%) and heart failure (2%). With the exception of warfarin and beta-blockers, national essential medicines were available at more than 70% of facilities. Clinicians adhered to clinical protocols at approximately 70% agreement with evaluators. CONCLUSION: The government of Rwanda was able to scale a nurse-led outpatient NCD programme to all first-level hospitals with good fidelity, feasibility and penetration as to expand access to care for severe NCDs.

Towards elimination of mother-to-child transmission of HIV in Rwanda: a nested case-control study of risk factors for transmission.

BACKGROUND: Mother-to-child HIV transmission (MTCT) has substantially declined since the scale-up of prevention programs around the world, including Rwanda. To achieve full elimination of MTCT, it is important to understand the risk factors associated with residual HIV transmission, defined as MTCT at the population-level that still occurs despite universal access to PMTCT. METHODS: We performed a case control study of children born from mothers with HIV with known vital status at 18 months from birth, who were followed in three national cohorts between October and December 2013, 2014, and 2015 in Rwanda. Children with HIV were matched in a ratio of 1:2 with HIV-uninfected children and a conditional logistic regression model was used to investigate risk factors for MTCT. RESULTS: In total, 84 children with HIV were identified and matched with 164 non-infected children. The median age of mothers from both groups was 29 years (interquartile range (IQR): 24-33). Of these mothers, 126 (51.4 %) initiated antiretroviral therapy (ART) before their pregnancy on record. In a multivariable regression analysis, initiation of ART in the third trimester (Adjusted Odds Ratio [aOR]: 9.25; 95 % Confidence Interval [95 % CI]: 2.12-40.38) and during labour or post-partum (aOR: 8.87; 95 % CI: 1.92-40.88), compared to initiation of ART before pregnancy, increased the risk of MTCT. Similarly, offspring of single mothers (aOR: 7.15; 95 % CI: 1.15-44.21), and absence of postpartum neonatal ART prophylaxis (aOR: 7.26; 95 % CI: 1.66-31.59) were factors significantly associated with MTCT. CONCLUSIONS: Late ART initiation for PMTCT and lack of postpartum infant prophylaxis are still the most important risk factors to explain MTCT in the era of universal access. Improved early attendance at antenatal care, early ART initiation, and enhancing the continuum of care especially for single mothers is crucial for MTCT elimination in Rwanda.

Addressing the mental health needs of children affected by HIV in Rwanda: validation of a rapid depression screening tool for children 7-14 years old.

BACKGROUND: Depression in children presents a significant health burden to society and often co-exists with chronic illnesses, such as human immunodeficiency virus (HIV). Research has demonstrated that 10-37% of children and adolescents living with HIV also suffer from depression. Low-and-middle income countries (LMICs) shoulder a disproportionate burden of HIV among other health challenges, but reliable estimates of co-morbid depression are lacking in these settings. Prior studies in Rwanda, a LMIC of 12 million people in East Africa, found that 25% of children living with HIV met criteria for depression. Though depression may negatively affect adherence to HIV treatment among children and adolescents, most LMICs fail to routinely screen children for mental health problems due to a shortage of trained health care providers. While some screening tools exist, they can be costly to implement in resource-constrained settings and are often lacking a contextual appropriateness. METHODS: Relying on international guidelines for diagnosing depression, Rwandan health experts developed a freely available, open-access Child Depression Screening Tool (CDST). To validate this tool in Rwanda, a sample of 296 children with a known diagnosis of HIV between ages 7-14 years were recruited as study participants. In addition to completing the CDST, all participants were evaluated by a mental health professional using a structured clinical interview. The validity of the CDST was assessed in terms of sensitivity, specificity, and a receiver operating characteristic (ROC) curve. RESULTS: This analysis found that depression continues to be a co-morbid condition among children living with HIV in Rwanda. For identifying these at-risk children, the CDST had a sensitivity of 88.1% and specificity of 96.5% in identifying risk for depression among children living with HIV at a cutoff score of 6 points. This corresponded with an area under the ROC curve of 92.3%. CONCLUSIONS: This study provides evidence that the CDST is a valid tool for screening depression among children affected by HIV in a resource-constrained setting. As an open-access and freely available tool in LMICs, the CDST can allow any health practitioner to identify children at risk of depression and refer them in a timely manner to more specialized mental health services. Future work can show if and how this tool has the potential to be useful in screening depression in children suffering from other chronic illnesses.

Evaluation of the implementation process of the mobile health platform 'WelTel' in six sites in East Africa and Canada using the modified consolidated framework for implementation research (mCFIR).

BACKGROUND: Health systems globally are investing in integrating secure messaging platforms for virtual care in clinical practice. Implementation science is essential for adoption, scale-up, spread and maintenance of complex evidence-based solutions in clinics with evolving priorities. In response, the mobile Health (mHealth) Research Group modified the existing consolidated framework for implementation research (CFIR) to evaluate implementation of virtual health tools in clinical settings. WelTel® is an evidence-based digital health platform widely deployed in various geographical and health contexts. The objective is to identify the facilitators and barriers for implementing WelTel and to assess the application of the mCFIR tool in facilitating focus groups in different geographical and health settings. METHODS: Both qualitative and descriptive quantitative approaches were employed. Six mCFIR sessions were held in three countries with 51 key stakeholders. The mCFIR tool consists of 5 Domains and 25 constructs and was distributed through Qualtrics Experience Management (XM). "Performance" and "Importance" scores were valued on a scale of 0 to 10 (Mean ± SD). Descriptive analysis was conducted using R computing software. NVivo 12 Pro software was used to analyze mCFIR responses and to generate themes from the participants' input. RESULTS: We observed a parallel trend in the scores of Importance and Performance. Of the five Domains, Domain 4 (End-user Characteristics) and Domain 3 (Inner Settings) scored highest in Importance (8.9 ± 0.5 and 8.6 ± 0.6, respectively) and Performance (7.6 ± 0.7 and 7.2 ± 1.3, respectively) for all sites. Domain 2 (Outer Setting) scored the lowest in both Importance and Performance for all sites (7.6 ± 0.4 and 5.6 ± 1.8). The thematic analysis produced the following themes: for areas of strengths, the themes brought up were timely diagnosis and response, cost-effectiveness, and user-friendliness. As for areas for improvement, the themes discussed were training, phone accessibility, stakeholder engagement, and literacy. CONCLUSION: The mCFIR tool allowed for a comprehensive understanding of the barriers and facilitators to the implementation, reach, and scale-up of digital health tools. Amongst several important findings, we observed the value of bringing the perspectives of both end users (HCPs and patients) to the table across Domains. TRIAL REGISTRATION: NCT02603536 - November 11, 2015: WelTelOAKTREE: Text Messaging to Support Patients With HIV/AIDS in British Columbia (WelTelOAKTREE). NCT01549457 - March 9, 2012: TB mHealth Study-Use of Cell Phones to Improve Compliance in Patients on LTBI Treatment.

Patient and healthcare provider experiences of hepatitis C treatment with direct-acting antivirals in Rwanda: a qualitative exploration of barriers and facilitators.

BACKGROUND: Direct-acting antivirals (DAAs) are increasingly accessible to patients with hepatitis C (HCV) worldwide and are being introduced through national health systems in sub-Saharan Africa. DAAs are highly efficacious when tested in controlled trials, yet patients treated outside of study settings often encounter challenges in completing the full treatment and follow-up sequence. Little information is available on the influences of successful DAA implementation in sub-Saharan Africa. This qualitative study explored the individual- and system-level barriers and enablers of DAA treatment in Rwanda between March 2015 and November 2017. METHODS: Face-to-face interviews were conducted with 39 patients who initiated care at one of four referral hospitals initially offering DAAs. Ten healthcare providers who managed HCV treatment participated in face-to-face interviews to examine system-level barriers and facilitators. Interview data were analyzed using a general inductive approach in alignment with the a priori objective of identifying barriers and facilitators of HCV care. RESULTS: Barriers to successful treatment included patients' lack of knowledge surrounding HCV and its treatment; financial burdens associated with paying for medication, laboratory testing, and transportation; the cumbersome nature of the care pathway; the relative inaccessibility of diagnostics technology; and heavy workloads of healthcare providers accompanied by a need for additional HCV-specific training. Patients and healthcare providers were highly aligned on individual- and system-level barriers to care. The positive patient-provider relationship, strong support from community and family members, lack of stigma, and mild side effect profile of DAAs all positively influenced patients' engagement in treatment. CONCLUSIONS: Several interrelated factors acted as barriers and facilitators to DAA treatment in Rwanda. Patients' and healthcare providers' perceptions were in agreement, suggesting that the impeding and enabling factors were well understood by both groups. These results can be used to enact evidence-informed interventions to help maximize the impact of DAAs as Rwanda moves towards HCV elimination.

Viral load detection and management on first line ART in rural Rwanda.

BACKGROUND: To achieve the ambitious 90-90-90 UNAIDS targets, access to routine viral load (VL) is critical. To measure VL, Rwanda has relied on a national reference laboratory for years. In 2014, a VL testing platform was implemented in a rural District in the Northern Province. Here we analyze the uptake of VL testing, identification of risks for detectable VL (≥1000 copies/ml), and the management of patients with a detectable VL. METHODS: A retrospective cohort study of patients who started ART between July 2012 and June 2015 and followed until end December 2016. Using descriptive statistics, we describe the VL cascade, from VL uptake to the start of second-line ART in patients diagnosed with virological failure. We estimate predictors of having a detectable VL using logistic regression. RESULTS: The uptake of VL testing increased progressively between 2013 and 2016, raising from 25.6% (39/152) in 2013 up to 93.2% (510/547) in 2016.In 2016, 88.5% (n = 451) of patients tested, had a suppressed VL. Predictors of having a detectable VL included being male (aOR 2.1; 95%CI 1.12-4.02; p = 0.02), being a sex worker (aOR 6.4; 95%CI 1.1-36.0; p = 0.04), having a WHO clinical stage IV when starting ART (aOR 8.8; 95%CI 1.8-43.0; p < 0.001), having had a previous detectable VL (aOR 7.2; 95%CI 3.5-14.5; p < 0.001), and having had no VL before 2016 (aOR 3.1; 95%CI 1.2-8.1; p = 0.02). Among patients with initial detectable VL between 2013 and 2016, 88% (n = 103) had a follow-up VL, of whom 60.2% (n = 62) suppressed their VL below 1000 copies/ml. The median time between the initial and follow-up VL was of 12.5 months (IQR: 8.7-19.0). Among patients with confirmed treatment failure, 63.4% (n = 26) started second-line ART within the study period. CONCLUSION: VL uptake increased after decentralizing VL testing in rural Rwanda. Virological suppression was high. An individualized follow up of patients at risk of non-suppression and a prompt management of patients with detectable VL may help to achieve and sustain the third global UNAIDS target: virological suppression in 90% of patients on ART.

Retention in care and virological failure among adult HIV+ patients on second-line ART in Rwanda: a national representative study.

BACKGROUND: Currently, there is limited evidence on the effectiveness of second-line antiretroviral therapy (ART) in sub-Saharan Africa. To address this challenge, outcomes of second-line protease inhibitor (PI) based ART in Rwanda were assessed. METHODS: A two-stage cluster sampling design was undertaken. 49 of 340 health facilities linked to the open-source electronic medical record (EMR) system of Rwanda were randomly sampled. Data sampling criteria included adult HIV positive patients with documented change from first to second-line ART regimen. Retention in care and treatment failure (viral load above 1000 copies/mL) were evaluated using multivariable Cox proportional hazards and logistic regression models. RESULTS: A total of 1688 patients (60% females) initiated second-line ART PI-based regimen by 31st December 2016 with a median follow-up time of 26 months (IQR 24-36). Overall, 92.5% of patients were retained in care; 83% achieved VL ≤ 1000 copies/ml, 2.8% were lost to care and 2.2% died. Defaulting from care was associated with more recent initiation of ART- PI based regimen, CD4 cell count ≤500 cells/mm3 at initiation of second line ART and viral load > 1000 copies/ml at last measurement. Viral failure was associated with younger age, WHO stage III&IV at ART initiation, CD4 cell count ≤500 cells/mm3 at switch, atazanavir based second-line ART and receiving care at a health center compared to hospital settings. CONCLUSIONS: A high proportion of patients on second-line ART are doing relatively well in Rwanda and retained in care with low viral failure rates. However, enhanced understandings of adherence and adherence interventions for less healthy individuals are required. Routine viral load measurement and tracing of loss to follow-up is fundamental in resource limited settings, especially among less healthy patients.