Hepatitis C Elimination in Rwanda: Progress, Feasibility, and Economic Evaluation.

OBJECTIVES: In 2018, Rwanda launched a national program to eliminate the hepatitis C virus (HCV). We aim to assess the impact of the program to date and identify strategies to achieve the World Health Organization's HCV elimination goals by 2030. METHODS: We developed a microsimulation model to simulate Rwanda's HCV epidemic from 2015 through 2050 and evaluated temporal trends in HCV infection, prevalence, mortality, and the total cost of care for scenarios that could achieve HCV elimination by 2030. RESULTS: Between 2018 and 2022, over 7 million people were screened for HCV, and 60 000 were treated. The study projected that Rwanda could achieve HCV elimination as early as 2027. A feasible strategy of an annual screening rate of 15% and a treatment rate of 100% would achieve all World Health Organization elimination goals by 2028, requiring screening an additional 4 million people and treating 23 900 patients by 2030. The elimination strategy costs $25 million for screening and diagnosis and $21 million for treatment from 2015 to 2050. The national program would avert 4900 hepatocellular carcinoma cases and 6700 HCV-related deaths and save the health system $25.33 million from 2015 to 2050. CONCLUSIONS: Rwanda is poised to become one of the first countries in the world to eliminate HCV. Rwanda's program serves as a blueprint for other countries in the African region. By rapid screening and treatment scale-up (eg, by leveraging HIV platforms) and by drug price negotiations, HCV elimination is not only feasible but can be cost-saving in low-income settings.

Prevalence of hepatitis B and C infection and linkage to care among patients with Non-Communicable Diseases in three rural Rwandan districts: a retrospective cross-sectional study.

INTRODUCTION: Rwanda's Hepatitis C elimination campaign has relied on mass screening campaigns. An alternative "micro-elimination" strategy focused on specific populations, such as non-communicable disease (NCD) patients, could be a more efficient approach to identifying patients and linking them to care. METHODS: This retrospective cross-sectional study used routine data collected during a targeted screening campaign among NCD patients in Kirehe, Kayonza, and Burera districts of Rwanda and patients receiving oncology services from the Butaro District Hospital. The campaign used rapid diagnostic tests to screen for Hepatitis B surface antigen (HBsAg) and Hepatitis C antibody (anti-HCV). We reported prevalences and 95% confidence intervals for HBsAg and anti-HCV, assessed for associations between patients' clinical programs and hepatitis B and C, and reported cascade of care for the two diseases. RESULTS: Out of 7,603 NCD patients, 3398 (45.9%) self-reported a prior hepatitis screening. Prevalence of HBsAg was 2.0% (95% CI: 1.7%-2.3%) and anti-HCV was 6.7% (95% CI: 6.2%-7.3%). The prevalence of HBsAg was significantly higher among patients < 40 years (2.4%). Increased age was significantly associated with anti-HCV (12.0% among patients ≥ 70 years). Of the 148 individuals who screened positive for HbsAg, 123 had viral load results returned, 101 had detectable viral loads (median viral load: 451 UI/mL), and 12 were linked to care. Of the 507 individuals who screened positive for anti-HCV, 468 had their viral load results returned (median viral load: 1,130,000 UI/mL), 304 had detectable viral loads, and 230 were linked to care. CONCLUSION: Anti-HCV prevalence among Rwandan patients with NCD was high, likely due to their older age. NCD-HCV co-infected patients had high HCV viral loads and may be at risk of poor outcomes from hepatitis C. Hepatitis C micro-elimination campaigns among NCD patients are a feasible and acceptable strategy to enhance case detection in this high-prevalence population with elevated viral loads and may support linkage to care for hepatitis C among elderly populations.

Lessons learned from global hepatitis C elimination programs.

In 2016, World Health Organization (WHO) introduced global targets for the care and management of hepatitis C virus (HCV) infection to eliminate hepatitis C as a public health threat by 2030. Despite significant improvements in testing and treatment, in 2020 only 23% of all persons infected with HCV globally were diagnosed. We explore examples from global hepatitis C programs in Georgia, Rwanda, and Nigeria that have used decentralized and integrated models to increase access to HCV testing. Georgia established the world's first national hepatitis C elimination program in 2015. In 2022, 2.6 million people (80% of the adults) have been screened for antibodies for HCV infection, and 80,000 persons with HCV virus detected were treated. To achieve these results, Georgia implemented HCV core antigen (HCVcAg) testing, utilization of point-of-care HCV RNA, and simplification of HCV viremia detection by qualitative HCV RNA. Rwanda was the first country in sub-Saharan Africa to commit to HCV elimination in 2018, and as of 2022 it has achieved its screening target of 7 million people and initiated approximately 60,000 patients on hepatitis C treatment by rapid decentralization and integration of HCV services. In Nigeria, the integrated near-point-of-care testing approach in Nasarawa state has been effective in expanding access to HCV viremia testing and enabling the possibility of same-day testing and treatment initiation. Examples of decentralization and integration of HCV testing and linkage to care in Georgia, Rwanda and Nigeria could help inform effective strategies to reach 2030 hepatitis C elimination goals in other countries.

Strategies for Removal of Barriers to Hepatitis C Elimination in Sub-Saharan Africa.

Hepatitis C virus (HCV) infection is a major global health threat, with serious consequences including liver cirrhosis and cancer. Despite efforts to combat HCV, an estimated 1.5 million new infections occur each year and HCV was the sixth leading cause of death in 2017. Nevertheless, political leaders are increasingly interested in the fight against HCV, and the achievements of countries such as Rwanda, Egypt, India, Mongolia, Pakistan, Georgia, and Ukraine have given hope that the elimination plan to reduce new infections to 90% and mortality to 65% by 2030 is possible. It is true that some African countries can attest to the difficulty of operationalizing the HCV program with expensive testing platforms and HCV drugs that few could afford in the past, let alone the logistics involved, given that active case detection is an asset for HCV elimination. The inability to add direct-acting antivirals (DAAs) to the national essential drug list and negotiate DAA cost subsidies remains a major challenge in Africa. The lessons learned from implementing and scaling up the human immunodeficiency virus program can provide a strong framework to deliver comprehensive HCV services. We present the strategies used by some African countries to move toward HCV elimination, describe the challenges they have faced, and suggest realistic solutions.

The Cascade of Care for Hepatitis C Treatment in Rwanda: A Retrospective Cohort Study of the 2017-2019 Mass Screening and Treatment Campaign.

Access to hepatitis C (HCV) testing and treatment is still limited globally. To address this, the Government of Rwanda launched a voluntary mass screening and treatment campaign in 2017. We studied the progression of patients through the cascade of HCV care during this campaign. We conducted a retrospective cohort study and included all patients screened at 46 hospitals between April 2017 and October 2019. We used hierarchical logistic regression to assess factors associated with HCV positivity, gaps in care, and treatment failure. A total of 860,801 people attended the mass screening during the study period. Some 5.7% tested positive for anti-HCV, and 2.9% were confirmed positive. Of those who were confirmed positive, 52% initiated treatment, and 72% of those initiated treatment, completed treatment and returned for assessment 12 weeks afterward. The cure rate was 88%. HCV positivity was associated with age, socio-economic status, sex, marital status, and HIV coinfection. Treatment failure was associated with cirrhosis, baseline viral load, and a family history of HCV. Our results suggest that future HCV screening and testing interventions in Rwanda and other similar settings should target high-risk groups. High dropout rates suggest that more effort should be put into patient follow-up to increase adherence to care.

Epidemiology of sexually transmitted infections: trends among patients screened for sexually transmitted infections in rwandan health facilities 2014-2020.

BACKGROUND: Sexually Transmitted Infections (STIs) are of great global health concern. Currently, there are limited epidemiological data characterizing STIs in the general population in Rwanda. We assessed the national and regional epidemiology of STIs in Rwanda from 2014-2020 among patients syndromically screened for STIs in all health facilities in Rwanda. METHODS: This is a retrospective analysis of the trend of STIs epidemiology among screened patients at all health facilities in Rwanda using data from the Health Management Information System (HMIS) reporting. Adult patients (15 years and over) screened for STIs between July 2014 and June 2020 were included in the analysis. Outcomes of interest were the number of individuals screened for STIs and individuals diagnosed with at least one STI with a syndromic approach only or plus a test together. RESULTS: Overall, the number of individuals screened for STIs over the study period was 5.3 million (M) in 2014-2015, 6.6 M in 2015-2016, 6.3 M in 2016-2017, 6.7 M in 2017-2018, 6.2 M in 2018-2019, and 4.9 M in 2019-2020. There was a modest increase in the number of individuals diagnosed and treated for STIs from 139,357 in 2014-15 to 202,294 (45% increase) in 2019-2020. At the national level, the prevalence of STI syndromes amongst individuals screened at health facilities in Rwanda varied between 2.37% to 4.16% during the study period. Among the provinces, Kigali city had the highest prevalence for the whole 6 years ranging from 3.46% (95%CI: 3.41, 3.51) in 2014-2015 to 8.23% (95%CI: 8.15, 8.31) in 2019-2020. CONCLUSION: From 2014 to 2020, the number of patients screened for STI syndromes in Rwanda varied between 4.9 M and 6.7 M. However, the prevalence of STIs among screened patients increased considerably over time, which could be associated with public awareness and improved data recording. The highest prevalence of all STIs was observed in urban areas and near borders, and private clinics reported more cases, suggesting the need to improve awareness in these settings and increase confidentiality and trust in public health clinics.

Time to complete hepatitis C cascade of care among patients identified during mass screening campaigns in rural Rwanda: a retrospective cohort study.

BACKGROUND: Since the discovery of direct-acting antivirals, treatment for hepatitis C virus (HCV) is increasingly accessible in low-resource settings, but quality of care in these settings is not known. We described progression through the cascade of care among individuals who screened positive for HCV antibodies during a mass screening campaign in Kirehe and Kayonza, two rural Rwandan districts, in September 2019. METHODS: This retrospective cohort study used routine clinical data to assess proportions of participants completing each stage of the cascade of care, including: (a) screening positive on rapid diagnostic test; (b) return of initial viral load results; (c) detectable viral load; (d) treatment assessment; (e) treatment initiation; (f) return of sustained virological response (SVR12) results; and (g) achieving SVR12. We proposed three indicators to assess timely care provision and used medians and interquartile ranges (IQR) to describe the time to complete the cascade of care. RESULTS: Overall, 666 participants screened HCV positive, among them, 452 (68.1%) were female and median age was 61 years (IQR: 47, 70). Viral load results were returned for 537 (80.6%) participants of whom 448 (83.4%) had detectable viral loads. Of these, 398 (88.8%) were assessed for treatment, 394 (99%) were initiated, but only 222 (56.3%) had results returned for SVR12. Among those with SVR12 results, 208 (93.7%) achieved SVR12. When assessing timely care provision, we found 65.9% (95% CI: 62.0, 69.7) of initial viral load results were returned ≤ 30 days of screening; 45% (95% CI: 40.1, 49.8) of people with detectable viral load completed treatment assessment ≤ 90 days of initial viral load results; and 12.5% (95% CI: 9.2, 16.3) of SVR12 results were returned ≤ 210 days of treatment initiation among those who initiated treatment. The overall median time from screening to SVR12 assessment was 437 days. CONCLUSION: Despite high rates of SVR12 among those who completed all stages of the cascade of care, we identified gaps and delays in the treatment cascade. Improving communication between viral load testing hubs and health facilities could reduce the turn-around time for viral load testing, and actively monitor timeliness of care provision could improve quality of HCV care.

Safety and efficacy of sofosbuvir-velpatasvir-voxilaprevir for re-treatment of chronic hepatitis C virus infection in patients with previous direct-acting antiviral treatment failure in Rwanda (SHARED-3): a single-arm trial.

BACKGROUND: Hepatitis C virus (HCV) genotype 4 non-a/d subtypes, which frequently have NS5A resistance-associated substitutions, are highly prevalent in sub-Saharan Africa. These subtypes, particularly genotype 4r, have been associated with higher rates of failure of treatment regimens containing the NS5A inhibitors ledipasvir or daclatasvir, which are the most accessible direct-acting antivirals in low-income countries. Clinical evidence regarding the efficacy of re-treatment options for these subtypes is limited. We aimed to evaluate the safety and efficacy of sofosbuvir-velpatasvir-voxilaprevir for the treatment of adults in Rwanda with chronic HCV infection, predominantly of genotype 4, and a history of direct-acting antiviral treatment failure. METHODS: In this single-arm prospective trial, we enrolled adults (aged ≥18 years) with a HCV RNA titre of at least 1000 IU/mL, and a documented history of direct-acting antiviral failure. Patients were assessed for eligibility at a single study site after referral from hospitals with HCV treatment programmes throughout Rwanda, and participants for whom sofosbuvir-ledipasvir treatment had failed in the previous SHARED trial were also included. Participants with decompensated liver disease or hepatitis B virus co-infection were excluded. Participants were treated once daily with an oral fixed-dose combination tablet containing sofosbuvir (400 mg), velpatasvir (100 mg), and voxilaprevir (100 mg) for 12 weeks. The primary endpoint was the proportion of participants with a sustained virological response 12 weeks after completion of treatment (SVR12) in the intention-to-treat population. Viral sequencing of NS3, NS5A, and NS5B genes was done at baseline in all participants and at end of follow-up (week 24) in participants with treatment failure. The study is registered with ClinicalTrials.gov (NCT03888729) and is completed. FINDINGS: Between Sept 23, 2019, and Jan 10, 2020, 49 individuals were screened and 40 participants were enrolled. 20 (50%) were female, 20 (50%) were male, median age was 63 years (IQR 56-68), and median HCV viral load was 6·2 log10 IU/mL (5·8-6·5) at baseline. The genotype subtypes identified were 4r (18 [45%] participants), 4k (six [15%]), 4b (five [13%]), 4q (four [10%]), 4l (two [5%]), 4a (one [3%]), 4m (one [3%]), and 3h (one [3%]). One (3%) genotype 4 isolate could not be subtyped, and one (3%) isolate was of unknown genotype. All successfully sequenced isolates (33 [83%]) had at least two NS5A resistance-associated substitutions and 25 (63%) had three or more. 39 (98% [95% CI 87-100]) participants had SVR12. Seven (18%) participants had a total of ten grade 3, 4, or 5 adverse events, including three (8%) cases of hypertension, and one (3%) case each of cataract, diabetes, gastrointestinal bleeding, joint pain, low back pain, vaginal cancer, and sudden death. Four of these events were categorised as serious adverse events resulting in hospitalisation. The one sudden death occurred at home from an unknown cause 4 weeks after the completion of treatment. No serious adverse event was determined to be related to the study drug or resulted in treatment discontinuation. INTERPRETATION: A 12 week course of sofosbuvir-velpatasvir-voxilaprevir is safe and efficacious for the re-treatment of individuals infected with HCV genotype 4 non-a/d subtypes with frequent baseline NS5A resistance-associated substitutions, following failure of previous direct-acting antiviral treatment. Improved affordability and access to sofosbuvir-velpatasvir-voxilaprevir in regions with these subtypes is crucial. FUNDING: Gilead Sciences.

Safety and efficacy of sofosbuvir-velpatasvir to treat chronic hepatitis C virus infection in treatment-naive patients in Rwanda (SHARED-3): a single-arm trial.

BACKGROUND: Hepatitis C virus (HCV) genotype 4 is the predominant type of HCV found in sub-Saharan Africa. Various genotype 4 subtypes, such as 4r, frequently have resistance-associated substitutions that can increase rates of treatment failure with common direct-acting antiviral regimens. In-vitro studies suggest that the NS5A inhibitor velpatasvir is effective against viral isolates containing such resistance-associated substitutions, but its clinical efficacy against genotype 4 non-a/d subtypes in sub-Saharan Africa remains to be confirmed. We aimed to evaluate the safety and efficacy of sofosbuvir-velpatasvir among adults chronically infected with HCV and naive to direct-acting antiviral treatment in Rwanda, where genotype 4 non-a/d subtypes predominate. METHODS: In this single-arm prospective trial, we enrolled adults (age ≥18 years) in Rwanda who had chronic HCV infection and a plasma HCV RNA titre of at least 1000 IU/mL. Patients were referred from hospitals with HCV treatment programmes throughout Rwanda and were sequentially enrolled and assessed for eligibility at a single study site. Individuals with decompensated liver disease or hepatitis B virus co-infection were excluded. Participants were given an oral fixed-dose combination tablet of sofosbuvir (400 mg) and velpatasvir (100 mg) once-daily for 12 weeks. The primary endpoint was the proportion of participants with a sustained virological response 12 weeks after completion of treatment (SVR12) in the intention-to-treat population. Viral sequencing of the NS5A and NS5B genes was done at baseline for all participants and end of follow-up (week 24) for participants who did not have SVR12. This study is registered with ClinicalTrials.gov (NCT03888729) and is completed. FINDINGS: Between Sept 23, 2019, and Jan 10, 2020, 73 individuals were screened for eligibility, of whom 12 (16%) were excluded and 61 (84%) were enrolled. 40 (66%) participants were female, 21 (34%) were male, median age was 64 years (IQR 51-74), and median baseline HCV viral load was 5·7 log10 IU/mL (5·2-6·2). The genotypes identified among the participants were 4k (28 [46%] participants), 4r (11 [18%]), 4v (eight [13%]), 4q (five [8%]), 4l (three [5%]), 4b (one [2%]), 4c (one [2%]), and one undetermined genotype 4 subtype. Three isolates could not be sequenced and were of indeterminate genotype. Of the 55 HCV isolates that were successfully sequenced, all had at least two NS5A resistance-associated substitutions. 59 (97% [95% CI 89-99]) participants had SVR12. 18 (30%) participants had grade 3 adverse events (including 12 [20%] with hypertension), and none had grade 4 adverse events. Four (7%) participants had serious adverse events, including one asthma exacerbation, one abscess, one uterine myoma, and one pelvic fracture related to a motor vehicle accident. No serious adverse events were attributed to the study drug and no adverse event resulted in discontinuation of the study drug. INTERPRETATION: A 12-week regimen of sofosbuvir-velpatasvir is safe and efficacious in treating chronic HCV genotype 4 infection in patients in Rwanda. This regimen could be an effective treatment option in regions known to have a high prevalence of HCV genotype 4 of diverse non-a/d subtypes. FUNDING: Gilead Sciences.

Values and preferences for hepatitis C self-testing among the general population and healthcare workers in Rwanda.

BACKGROUND: In 2018, Rwanda launched a 5-year hepatitis C virus (HCV) elimination plan as per the World Health Organization global targets to eliminate HCV by 2030. To improve awareness of HCV status, strategies are needed to ensure easy access to HCV testing by as-yet unreached populations. HCV-self-testing, an innovative strategy, could further increase HCV testing uptake. This assessment explores perceptions around HCV self-testing among members of the public and healthcare workers in Rwanda. METHODS: A qualitative study was undertaken in Masaka District Hospital, comprising individual interviews, group interviews and participatory action research (PAR) activities. Purposive and snowball sampling methods guided the selection of informants. Informed consent was obtained from all participants. A thematic analysis approach was used to analyse the findings. RESULTS: The participants comprised 36 members of the public and 36 healthcare workers. Informants appreciated HCV self-testing as an innovative means of increasing access to HCV testing, as well as an opportunity to test privately and subsequently autonomously decide whether to seek further HCV care. Informants further highlighted the need to make HCV self-testing services free of charge at the nearest health facility. Disadvantages identified included the lack of pre/post-test counselling, as well as the potential psychosocial harm which may result from the use of HCV self-testing. CONCLUSION: HCV self-testing is perceived to be an acceptable method to increase HCV testing in Rwanda. Further research is needed to assess the impact of HCV self-testing on HCV cascade of care outcomes.

Prevalence and associated risk factors for hepatitis B and C viruses among refugee populations living in Mahama, Rwanda: A cross-sectional study.

INTRODUCTION: As part of the integration of refugees into Rwanda's national hepatitis C elimination agenda, a mass screening campaign for hepatitis B (HBV) and hepatitis C (HCV) was conducted among Burundian refugees living in Mahama Camp, Eastern Rwanda. This cross-sectional survey used data from the screening campaign to report on the epidemiology of viral hepatitis in this setting. METHODS: Rapid diagnostic tests (RDTs) were used to screen for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) among people of ≥15years old. We calculated seroprevalence for HBsAg and anti-HCV by age and sex and also calculated age-and-sex adjusted risk ratios (ARR) for other possible risk factors. RESULTS: Of the 26,498 screened refugees, 1,006 (3.8%) and 297 (1.1%) tested positive for HBsAg and Anti-HCV, respectively. HBsAg was more prevalent among men than women and most common among people 25-54 years old. Anti-HCV prevalence increased with age group with no difference between sexes. After adjusting for age and sex, having a household contact with HBsAg was associated with 1.59 times higher risk of having HBsAg (95% CI: 1.27, 1.99) and having a household contact with anti-HCV was associated with 3.66 times higher risk of Anti-HCV (95% CI: 2.26, 5.93). Self-reporting having HBV, HCV, liver disease, or previously screened for HBV and HCV were significantly associated with both HBsAg and anti-HCV, but RDT-confirmed HBsAg and anti-HCV statuses were not associated with each other. Other risk factors for HBsAg included diabetes (ARR = 1.97, 95% CI: 1.08, 3.59) and family history of hepatitis B (ARR = 1.32, 95% CI: 1.11, 1.56) and for anti-HCV included heart disease (ARR = 1.91, 95% CI: 1.30, 2.80) and history of surgery (ARR = 1.70, 95% CI: 1.24, 2.32). CONCLUSION: Sero-prevalence and risks factors for hepatitis B and C among Burundian were comparable to that in the Rwandan general population. Contact tracing among household members of identified HBsAg and anti-HCV infected case may be an effective approach to targeted hepatitis screening given the high risk among self-reported cases. Expanded access to voluntary testing may be needed to improve access to hepatitis treatment and care in other refugee settings.

Initiation of hepatitis C treatment in two rural Rwandan districts: a mobile clinic approach.

BACKGROUND: To eliminate hepatitis C, Rwanda is conducting national mass screenings and providing to people with chronic hepatitis C free access to Direct Acting Antivirals (DAAs). Until 2020, prescribers trained and authorized to initiate DAA treatment were based at district hospitals, and access to DAAs remains expensive and geographically difficult for rural patients. We implemented a mobile clinic to provide DAA treatment initiation at primary-level health facilities among people with chronic hepatitis C identified through mass screening campaigns in rural Kirehe and Kayonza districts. METHODS: The mobile clinic team was composed of one clinician authorized to manage hepatitis, one lab technician, and one driver. Eligible patients received same-day clinical consultations, counselling, laboratory tests and DAA initiation. Using clinical databases, registers, and program records, we compared the number of patients who initiated DAA treatment before and during the mobile clinic campaign. We assessed linkage to care during the mobile clinical campaign and assessed predictors of linkage to care. We also estimated the cost per patient of providing mobile services and the reduction in out-of-pocket costs associated with accessing DAA treatment through the mobile clinic rather than the standard of care. RESULTS: Prior to the mobile clinic, only 408 patients in Kirehe and Kayonza had been initiated on DAAs over a 25-month period. Between November 2019 and January 2020, out of 661 eligible patients with hepatitis C, 429 (64.9%) were linked to care through the mobile clinic. Having a telephone number and complete address recorded at screening were strongly associated with linkage to care. The cost per patient of the mobile clinic program was 29.36 USD, excluding government-provided DAAs. Providing patients with same-day laboratory tests and clinical consultation at primary-level health facilities reduced out-of-pocket expenses by 9.88 USD. CONCLUSION: The mobile clinic was a feasible strategy for providing rapid treatment initiation among people chronically infected by hepatitis C, identified through a mass screening campaign. Compared to the standard of care, mobile clinics reached more patients in a much shorter time. This low-cost strategy also reduced out-of-pocket expenditures among patients. However, long-term, sustainable care would require decentralization to the primary health-centre level.

Risk factors for difficult-to-treat hepatitis C virus genotype 4r in Rwanda and implications for elimination in sub-Saharan Africa.

In sub-Saharan Africa, there exist distinct HCV genotype (GT) subtypes harbouring resistance-associated substitutions to commonly used non-structural protein 5A (NS5A) inhibitor-based direct-acting antiviral (DAA) regimens. In particular, GT4r subtype has demonstrated high rates of treatment failure. In the absence of routine viral sequencing in sub-Saharan Africa, it is important to identify sociodemographic, epidemiologic, and clinical characteristics that may be associated with GT4r infection. Methods: A secondary analysis was performed on data from 300 adults with HCV GT4 enrolled in a prospective trial assessing the safety and efficacy of sofosbuvir-ledipasvir in Rwanda in 2017. The association between characteristics at enrolment and GT subtype was assessed by chi-square analysis and logistic regression. In multivariate analysis, there were a higher proportion of participants with GT4r subtype with age <40 years (OR: 3.6, 95% CI: 1.3-10.5, p = 0.02), previous hospitalization (OR: 2.5, 95% CI: 1.3-5.0, p = 0.006), previous surgery (OR: 2.2, 95% CI: 1.1-4.2, p = 0.03), cirrhosis (OR: 3.2, 95% CI: 1.3-7.5, p = 0.008) and baseline HCV RNA >1 million IU/ml (OR: 3.4, 95% CI: 1.6-6.9, p = 0.001). Rwandan adults with GT4r are more likely to be younger, have a history of hospital admissions and surgeries and have more active or advanced liver disease compared to those with other GT4 subtypes. In the absence of advanced diagnostics to assess GT subtype, patients with these characteristics may warrant closer monitoring for treatment failure or alternative DAA regimens. More treatment experience with diverse DAA regimens is urgently needed for GT subtypes particular to this region.

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.

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.

Role of unsafe medical practices and sexual behaviours in the hepatitis B and C syndemic and HIV co-infection in Rwanda: a cross-sectional study.

OBJECTIVES: This study describes the burden of the hepatitis B, C and HIV co-infections and assesses associated risk factors. SETTING: This analysis used data from a viral hepatitis screening campaign conducted in six districts in Rwanda from April to May 2019. Ten health centres per district were selected according to population size and distance. PARTICIPANTS: The campaign collected information from 156 499 participants (51 496 males and 104 953 females) on sociodemographic, clinical and behavioural characteristics. People who were not Rwandan by nationality or under 15 years old were excluded. PRIMARY AND SECONDARY OUTCOMES: The outcomes of interest included chronic hepatitis C virus (HCV) infection, chronic hepatitis B virus (HBV) infection, HIV infection, co-infection HIV/HBV, co-infection HIV/HCV, co-infection HBV/HCV and co-infection HCV/HBV/HIV. Multivariable logistic regressions were used to assess factors associated with HBV, HCV and HIV, mono and co-infections. RESULTS: Of 156 499 individuals screened, 3465 (2.2%) were hepatitis B surface antigen positive and 83% (2872/3465) of them had detectable HBV desoxy-nucleic acid (HBV DNA). A total of 4382 (2.8%) individuals were positive for antibody-HCV (anti-HCV) and 3163 (72.2%) had detectable HCV ribo-nucleic acid (RNA). Overall, 36 (0.02%) had HBV/HCV co-infection, 153 (0.1%) HBV/HIV co-infection, 238 (0.15%) HCV/HIV co-infection and 3 (0.002%) had triple infection. Scarification or receiving an operation from traditional healer was associated with all infections. Healthcare risk factors-history of surgery or transfusion-were associated with higher likelihood of HIV infection with OR 1.42 (95% CI 1.21 to 1.66) and OR 1.48 (1.29 to 1.70), respectively, while history of physical traumatic assault was associated with a higher likelihood of HIV and HBV/HIV co-infections with OR 1.69 (95% CI 1.51 to 1.88) and OR 1.82 (1.08 to 3.05), respectively. CONCLUSIONS: Overall, mono-infections were common and there were differences in significant risk factors associated with various infections. These findings highlight the magnitude of co-infections and differences in underlying risk factors that are important for designing prevention and care programmes.

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.

Risk factors for viral hepatitis C infection in Rwanda: results from a nationwide screening program.

BACKGROUND: The epidemiology and risk factors for hepatitis C virus (HCV) infection in Rwanda are not well known; however, this information is crucial to shaping the country's public health approach to hepatitis C control. METHODS: A HCV screening campaign was conducted in the general population in 24 districts previously identified to have a high HCV disease burden. At the time of sample collection, sociodemographic information and self-reported risk factors were collected. Bivariate and multivariate logistic regressions were conducted to assess risk factors independently associated with hepatitis C antibodies (HCVAb) seroprevalence. RESULTS: Out of a total of 326,263 individuals screened for HCVAb, 22,183 (6.8%) were positive. In multivariate analysis, risk factors identified as statistically associated with HCVAb Seroprevalence include history of traditional operation or scarification (OR = 1.09, 95% CI: 1.05-1.14), presence of viral hepatitis in the family (OR = 1.27, 95% CI: 1.15-1.40), widowed or separated/divorced (OR = 1.36, 95% CI: 1.26-1.47), Southern province (OR = 1.98, 95% CI: 1.88-2.08) and aged 65 years and older (OR = 4.86, 95% CI: 4.62-5.11). Ubudehe category 3 (OR = 0.97, 95% CI: 0.93-1.01) and participants using RAMA (Health insurances for employees of public and private sectors) insurance (OR = 0.76, 95% CI: 0.70-0.85) had lower odds of HCV seroprevalence. CONCLUSIONS: Our findings provide important information for Rwanda's strategy on prevention and case-finding. Future prevention interventions should aim to reduce transmission through targeted messaging around traditional healing practices and case-finding targeting individuals with a history of exposure or advanced age.

Screening a nation for hepatitis C virus elimination: a cross-sectional study on prevalence of hepatitis C and associated risk factors in the Rwandan general population.

OBJECTIVES: We analysed data collected during programmatic screening activities conducted in 2017 to describe hepatitis C virus (HCV) seroprevalence in the general population and identify associated factors. DESIGN: We analysed data collected between June and September 2017. For both seroprevalence and viraemia, variations across demographic and geographic factors were assessed and multivariate regression models were fit to identify factors independently associated with each marker. Geospatial data were examined for visualisation. SETTING: HCV screening was organised within each of the 30 districts in Rwanda. One designated location in each district was selected as the screening site and screening took place for 1 week at each site. PARTICIPANTS: This study included 124 223 male and female volunteers. Anti-HCV-positive individuals were followed up with HCV RNA viral load (VL) testing for infection confirmation. MAIN OUTCOME MEASURES: Two markers were examined: the presence of HCV antibodies and HCV RNA VL. RESULTS: Among 124 223 individuals screened, 11 003 (8.86%, 95% CIs: 8.70% to 9.02%) were positive for anti-HCV. Anti-HCV prevalence varied by age with the oldest age group (>55 year olds) having a prevalence of 16.46% (95% CIs: 16.14% to 16.80%) and the youngest age group (<25 year olds) having a prevalence of 2.20% (95% CIs: 1.93% to 2.50%) (crude OR=8.78). After adjustment for covariates, an association remained between anti-HCV prevalence and age (p<0.001), province (p<0.001) and socioeconomic status (p<0.001). Of the 3771 anti-HCV-positive individuals who had an available HCV RNA VL result, 2099 (55.66%, 95% CI: 54.06% to 57.25%) had a detectable HCV RNA VL. Age was also associated with HCV viraemia (p<0.001). CONCLUSION: Results suggest that over 55% of individuals who screened positive for HCV-antibodies were chronically infected. Targeted screening for HCV among older individuals is recommended, given the association between age and infection. Further geographical hotspots of HCV infection can also inform targeted screening as Rwanda moves towards HCV elimination.

Prevalence of hepatitis B surface antigen (HBsAg) positivity and its associated factors in Rwanda.

BACKGROUND: The epidemiology of hepatitis B virus (HBV) infection in the general population in Rwanda is not well known. This study examined the prevalence of HBV surface antigen (HBsAg) positivity and associated risk factors among people aged 25 years and over in an organized national screening campaign. METHODS: This is a cross-sectional study using data from a nationwide HBV screening campaign organized by the Rwanda Biomedical Centre from March to October 2018. This campaign targeted individuals aged > 25 years old from 24 of 30 districts of Rwanda. Sensitization was done through multimedia announcements, community health workers and local church leaders. During the campaign, a structured interview was administered by trained healthcare workers to collect information on socio-demographic, clinical and behavioral characteristics of participants; HBV screening was performed with HBsAg using enzyme-linked immunosorbent assays (ELISA) testing. Bivariate and multivariate logistic regressions were used to assess factors associated with HBsAg positivity in the screened participants. RESULTS: A total of 327,360 individuals were screened during the campaign. Overall 12,865(3.9%) were HBsAg positive. The highest prevalence (4.2%) was found in the 35-44-year-old group, but the difference from other groups was not significant (Odds Ratio [OR = 1.057, 95% Confidence Interval(CI) (0.904-1.235)]. Being male [OR = 1.348, 95% CI (1.30,1.40)]; being single [OR = 1.092, 95% CI (1.10-1.16)] compared to married; a previous positive TB screening test [OR = 2.352, 95% CI (1.63-3.39)]; history of surgical operation [OR = 1.082, 95% CI (1.00,1.17)]; exposure to traditional operational practices and scarification [OR = 1.187, 95% CI (1.13, 1.24)]; and having a person in the family with viral hepatitis [OR = 1.367, 95% CI (1.21, 1.53)] were significantly associated with HBV infection. CONCLUSIONS: These data provide the first national estimate of the prevalence of HBsAg seropositivity and its associated factors in Rwanda. The study identified people with the highest risk of HBV infection who should be the priority of future prevention efforts in Rwanda and in similar settings.