Safety and Efficacy of Limited Laboratory Monitoring for Hepatitis C Treatment: A Blinded Clinical Trial in Rwanda.

Direct-acting antivirals for hepatitis C virus (HCV) are highly effective and well-tolerated. However, only a small percentage of HCV-infected individuals globally have received therapy. Reducing the complexity of monitoring during HCV therapy, if shown to be safe, could facilitate greater access to HCV services, particularly in resource-limited settings such as sub-Saharan Africa. We enrolled a total of 300 patients who were chronically infected with genotype 4 HCV in Rwanda and treated them with fixed-dose ledispasvir/sofosbuvir for 12 weeks. For 60 consecutive participants enrolled, we blinded the study clinician to on-treatment laboratory results. We compared the efficacy, safety, and tolerability in those with blinded laboratory results to those with standard laboratory monitoring. Baseline characteristics among those with blinded laboratory values were comparable to those with standard monitoring. Among both groups, the median age was 63 years, and the median HCV viral load was 5.9 log (versus 64 years and 6.0 log, respectively). Sustained virologic response rates at 12 weeks after treatment completion were similar in those with blinded laboratories (87%) compared to those with standard laboratory monitoring (87%). There was no increase in adverse events in those with blinded laboratory results, and no participants discontinued the study medication because of an adverse event. Conclusion: On-treatment laboratory monitoring did not improve patient outcomes in those treated with ledispasvir/sofosbuvir. Eliminating this monitoring in treatment programs in resource-limited settings may facilitate and accelerate scale-up of HCV therapy.

Treatment of chronic hepatitis C virus infection in Rwanda with ledipasvir-sofosbuvir (SHARED): a single-arm trial.

BACKGROUND: Limited treatment data are available for hepatitis C virus (HCV) in sub-Saharan Africa, especially for genotype 4. Our objective was to establish the safety and efficacy of ledipasvir-sofosbuvir for chronic HCV genotype 1 or 4 infection in adults in Rwanda. METHODS: We did a single-arm trial to evaluate the safety and efficacy of ledipasvir-sofosbuvir in Rwandan adults with chronic HCV infection at a single study site (Rwanda Military Hospital, Kigali, Rwanda). We enrolled individuals aged 18 years or older with HCV genotype 1 or 4 infection and a plasma HCV RNA concentration of more than 1000 IU/mL at screening. All participants were given ledipasvir (90 mg) and sofosbuvir (400 mg) in a single combination tablet once daily for 12 weeks. We established HCV genotype using an Abbott platform, and HCV subtype with PCR amplification. The primary endpoint was the proportion of participants with a sustained virological response 12 weeks after therapy (SVR12). All patients enrolled in the study were included in the primary endpoint analyses. This study is registered with ClinicalTrials.gov, number NCT02964091. FINDINGS: 300 participants were enrolled between Feb 6, 2017, and Sept 18, 2017, and the follow-up period was completed on March 1, 2018. On genotyping, 248 (83%) participants were reported as having genotype 4, four (1%) genotype 1, and 48 (16%) both genotype 1 and genotype 4. Subsequent viral sequencing showed all participants actually had genotype 4 infection with subtype 4k (134 [45%]), subtype 4r (48 [16%]), subtype 4q (42 [14%]), and subtype 4v (24 [8%]) predominating. Overall, 261 (87%, 95% CI 83-91) participants achieved SVR12. In participants with genotype 4r, SVR12 was observed in 27 (56%, 95% CI 41-71) participants versus 234 (93%, 90-96) individuals with other subtypes. There were no drug-related treatment discontinuations due to ledipasvir-sofosbuvir. The most common adverse events were hypertension (97 [32%]), headache (78 [26%]), dizziness (61 [20%]), and fatigue (56 [19%]). There were six serious adverse events; none were assessed to be due to the study drug. 296 participants had data for pill counts at week 4 and 8; 271 (92%) had 100% adherence and only one (<1%) had an adherence of less than 90%. INTERPRETATION: This is the first large-scale prospective study reporting direct-acting antiviral outcomes in sub-Saharan Africa. The high adherence and treatment success without intensive support measures or highly specialised clinical providers, and lack of treatment discontinuations due to adverse events support the feasibility of HCV treatment decentralisation and scale-up in sub-Saharan Africa. Genotype 4r is uniquely expressed in this region and associated with high rates of treatment failure, suggesting a need for rigorous test-of-cure in clinical practice and consideration of the use of newer pangenotypic direct-acting antiviral regimens in this region. FUNDING: Gilead Sciences.

Prevalence of Hepatitis C Virus Infection and Its Risk Factors among Patients Attending Rwanda Military Hospital, Rwanda.

In Rwanda, the prevalence of viral hepatitis (HCV) is poorly understood. The current study investigated the prevalence and risk factors of HCV infection in Rwanda. A total of 324 patients attending Rwanda Military Hospital were randomly selected and a questionnaire was administered to determine the risk factors. Blood was collected and screened for anti-HCV antibodies and seropositive samples were subjected to polymerase chain reaction method. Hematology abnormalities in the HCV infected patients were also investigated. Anti-HCV antibody and active HCV infection were found in 16.0% and 9.6% of total participants, respectively. Prevalence was highest (28.4%; 19/67) among participants above 55 years and least (2.4%; 3/123) among younger participants (18-35 years). There was a significant (P = 0.031) relationship between place of residence and HCV infection with residents of Southern Province having significantly higher prevalence. The hematological abnormalities observed in the HCV infected patients included leukopenia (48.4%; 15/52), neutropenia (6.5%; 2/52), and thrombocytopenia (25.8%; 8/52). The HCV infection was significantly higher in the older population (>55 years) and exposure to injection from traditional practitioners was identified as a significant (P = 0.036) risk factor of infection. Further studies to determine the factors causing the high prevalence of HCV in Rwanda are recommended.

Enhancing formal educational and in-service training programs in rural Rwanda: a partnership among the public sector, a nongovernmental organization, and academia.

Global disparities in the distribution, specialization, diversity, and competency of the health workforce are striking. Countries with fewer health professionals have poorer health outcomes compared with countries that have more. Despite major gains in health indicators, Rwanda still suffers from a severe shortage of health professionals.This article describes a partnership launched in 2005 by Rwanda's Ministry of Health with the U.S. nongovernmental organization Partners In Health and with Harvard Medical School and Brigham and Women's Hospital. The partnership has expanded to include the Faculty of Medicine and the School of Public Health at the National University of Rwanda and other Harvard-affiliated academic medical centers. The partnership prioritizes local ownership and-with the ultimate goals of strengthening health service delivery and achieving health equity for poor and underserved populations-it has helped establish new or strengthen existing formal educational programs (conferring advanced degrees) and in-service training programs (fostering continuing professional development) targeting the local health workforce. Harvard Medical School and Brigham and Women's Hospital have also benefited from the partnership, expanding the opportunities for training and research in global health available to their faculty and trainees.The partnership has enabled Rwandan health professionals at partnership-supported district hospitals to acquire new competencies and deliver better health services to rural and underserved populations by leveraging resources, expertise, and growing interest in global health within the participating U.S. academic institutions. Best practices implemented during the partnership's first nine years can inform similar formal educational and in-service training programs in other low-income countries.

Developing cancer control plans in Africa: examples from five countries.

The creation and implementation of national cancer control plans is becoming increasingly necessary for countries in Africa, with the number of new cancer cases per year in the continent expected to reach up to 1·5 million by 2020. Examples from South Africa, Egypt, Nigeria, Ghana, and Rwanda describe the state of national cancer control plans and their implementation. Whereas in Rwanda the emphasis is on development of basic facilities needed for cancer care, in those countries with more developed economies, such as South Africa and Nigeria, the political will to fund national cancer control plans is limited, even though the plans exist and are otherwise well conceived. Improved awareness of the increasing burden of cancer and increased advocacy are needed to put pressure on governments to develop, fund, and implement national cancer control plans across the continent.