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.

A cost analysis of the diagnosis and treatment of malaria at public health facilities and communities in three districts in Rwanda.

BACKGROUND: Malaria is a potentially fatal disease spread by the bites of Plasmodium-infected Anopheles mosquitoes. Despite long-term efforts to control malaria in Rwanda, malaria incidence increased from 48 to 403 cases/1000 individuals between 2012 and 2016. The diagnosis and treatment of malaria occurs at multiple levels, but the costs of these activities are not well understood. This research was conducted to estimate the direct medical costs incurred by the Ministry of Health in diagnosing and treating malaria in three districts of Rwanda in 2018. METHODS: A cross-sectional and retrospective costing analysis was conducted in three districts that represented low (5-200 cases per 1000 individuals), moderate (> 200-400 cases per 1000 individuals), and high (> 400 cases per 1000 individuals) endemicity regions. Data on malaria cases managed at three healthcare levels (community, health centre, district hospital) was obtained from national databases. The direct medical costs of cases per malaria severity ('simple malaria', 'simple malaria with minor digestive symptoms', and 'severe malaria') were calculated based on the minimum package of health services provided. Total costs for each of the three districts were also calculated. RESULTS: A total of 298,381 malaria cases were recorded in Burera, Kirehe, and Southern Kayonza districts in 2018. The average unit cost per case ranged from USD 1.36 (for simple malaria at the community level) to USD 92.80 (for severe malaria with cerebral complications at district hospitals). Simple malaria cases managed at health centres and district hospitals were more than two-fold (USD 2.99-USD 3.00) and more than eight-fold (USD 12.10-USD 12.12) higher, respectively, than those managed in the community (USD 1.36). Overall, the Ministry of Health incurred USD 645,647.68 in direct medical costs related to malaria management across the three districts in 2018. Changes in disease rates from different endemicity regions and costs of anti-malarial oral medications significantly impacted the study results. CONCLUSION: In Rwanda, severe malaria results in much higher expenses compared to other malaria types. Prompt diagnosis and appropriate treatment are crucial to prevent the progression of simple malaria to severe malaria, to reduce Ministry of Health malaria expenditures, and to reduce community transmission.

Characteristics and clinical outcomes of patients presenting with advanced HIV disease in the "treat all" era: a retrospective cohort study from rural Rwanda.

BACKGROUND: In 2016 Rwanda adopted "treat all" where all patients with HIV are immediately eligible for ART regardless of disease progression. Despite widespread availability of treatment, it is unknown whether presentation with advanced HIV persists. METHODS: We conducted a retrospective cohort among patients aged ≥ 15 who enrolled in care between July 2016 and July 2018 in three rural Rwandan districts. We estimated the prevalence of advanced HIV, defined as presenting with CD4 count < 200 cells/mm3 or WHO stage 3 or 4, and compared baseline characteristics of patients with and without advanced HIV. We compared cumulative incidences and time to events using Chi squared tests and Cox proportional hazards models, respectively, for (a) viral load tests; (b) viral suppression; (c) death; and (d) treatment failure (a composite of death, lost to follow up, or virologic failure). RESULTS: Among 957 patients, 105 (11.0%) presented with advanced HIV. These patients were significantly more likely to have low body mass index, come from Burera district, be older, and be identified through inpatient settings rather than through voluntary or prenatal testing. Patients with advanced HIV had significantly higher risks of death at 12-months (9.5% vs 1.5%, p < 0.001) and 18-months (10.5% vs 1.9%, p < 0.001) and significantly higher risk of treatment failure at 12-months (21.9% vs. 14.2%, p = 0.037). After adjusting for confounders, patients with advanced HIV had still higher rates of death (adjusted Hazard ratio [aHR] = 4.4, 95% CI: 1.9, 10.2, p < 0.001) and treatment failure (aHR = 1.7, 95% CI: 1.1, 2.5, p = 0.017), but no difference in viral load testing (aHR = 1.1, 95% CI: 0.8, 1.5, p = 0.442) or viral suppression (aHR = 1.0, 95% CI: 0.8, 1.4, p = 0.949). When allowing for the hazard ratio to vary over time, patients with advanced HIV experienced elevated rates of treatment failure in the first six of enrollment, but not after nine months. CONCLUSION: Presenting with advanced HIV remains common and is still associated with poor patient outcomes. Sensitization of the community to the benefits of early ART initiation, identification of patients with advanced HIV, and holistic support programs for the first 6 months of treatment may be needed to improve outcomes.

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.

Drug resistance mutations after the first 12 months on antiretroviral therapy and determinants of virological failure in Rwanda.

OBJECTIVE: To evaluate HIV drug resistance (HIVDR) and determinants of virological failure in a large cohort of patients receiving first-line tenofovir-based antiretroviral therapy (ART) regimens. METHODS: A nationwide retrospective cohort from 42 health facilities was assessed for virological failure and development of HIVDR mutations. Data were collected at ART initiation and at 12 months of ART on patients with available HIV-1 viral load (VL) and ART adherence measurements. HIV resistance genotyping was performed on patients with VL ≥1000 copies/ml. Multiple logistic regression was used to determine factors associated with treatment failure. RESULTS: Of 828 patients, 66% were women, and the median age was 37 years. Of the 597 patients from whom blood samples were collected, 86.9% were virologically suppressed, while 11.9% were not. Virological failure was strongly associated with age <25 years (adjusted odds ratio [aOR]: 6.4; 95% confidence interval [CI]: 3.2-12.9), low adherence (aOR: 2.87; 95% CI: 1.5-5.0) and baseline CD4 counts <200 cells/µl (aOR 3.4; 95% CI: 1.9-6.2). Overall, 9.1% of all patients on ART had drug resistance mutations after 1 year of ART; 27% of the patients who failed treatment had no evidence of HIVDR mutations. HIVDR mutations were not observed in patients on the recommended second-line ART regimen in Rwanda. CONCLUSIONS: The last step of the UNAIDS 90-90-90 target appears within grasp, with some viral failures still due to non-adherence. Nonetheless, youth and late initiators are at higher risk of virological failure. Youth-focused programmes could help prevent further drug HIVDR development.

Implementation and Adaptation of a Combined Economic Empowerment and Peer Support Program Among Youth Living With HIV in Rural Rwanda.

Background: Youth living with HIV in rural Rwanda experience poor clinical outcomes. In 2017, we implemented Adolescent Support Groups (ASGs), which provided economic incentives and peer support to youth aged 15-25. Methods: We assessed the ASG program using programmatic and electronic medical records. We described group composition and achievement on three indicators used to determine economic incentive levels: (1) quarterly pharmacy visit attendance, (2) biannual savings target achievement, and (3) annual viral suppression. Results: In total, 324 members enrolled in 34 ASGs. Group size and member ages varied more than anticipated. Groups performed well on pharmacy visit attendance (median quarterly group attendance range 91-100%) and on achieving savings targets (median biannual achievement range 80-83%). The viral suppression indicator could not be implemented as planned. Conclusion: To reflect contextual realities, adaptations in enrollment, indicator evaluation, and awarding of incentives occurred during implementation. Future research should assess whether these adaptations affected results.

Receipt of a combined economic and peer support intervention and clinical outcomes among HIV-positive youth in rural Rwanda: A retrospective cohort.

INTRODUCTION: To combat poor clinical outcomes among HIV-positive youth, Partners In Health/Inshuti Mu Buzima (PIH/IMB) implemented Adolescent Support Groups (ASGs), which combined peer support and group-based economic incentives to promote treatment adherence, economic empowerment, and viral suppression. This study assesses the association between ASG membership and clinical outcomes among HIV-positive youth living in rural Rwanda. METHODS: We constructed a retrospective cohort using PIH/IMB's electronic medical record (EMR) system. ASG members were matched to control youth within strata defined by health facility, year of birth, and whether the patient had enrolled in HIV services as a pediatric patient, as a PMTCT mother, or through another route. Our 12-month outcomes of interest were a) death-free retention in care, b) death-free retention with active follow-up, c) ≥80% adherence to appointment keeping, and d) viral load suppression (<20 copies/ml). We used generalized linear mixed models to estimate odds ratios for the association between ASG participation and each outcome. To mitigate possible unmeasured confounding, we additionally included participant data from the previous year and conducted a difference-in-difference analysis for each outcome to assess whether ASG members experienced greater changes compared to control youth over a similar period. RESULTS: Two-hundred sixty ASG members were identified in the EMR and matched to 209 control youth for analysis. After 12 months of follow-up, ASG members had similar outcomes to the control youth in terms of death-free retention (93% vs. 94%), death-free retention with active follow-up (79% vs. 78%), ≥80% adherence to appointment keeping (42% vs. 43%), and viral suppression (48% vs. 51%). We did not observe any significant associations between ASG participation and clinical outcomes in crude or adjusted models, nor did ASG members experience greater improvements than control youth in our difference-in-difference analysis. CONCLUSIONS: The ASG program did not improve retention, appointment adherence, or viral suppression among HIV positive youth in rural Rwanda. Challenges implementing the intervention as designed underscore the importance of incorporating implementation strategies and youth perspectives in program design. This population remains vulnerable to poor clinical outcomes, and additional research is needed to better serve youth living with HIV.

Rediscovering life after being diagnosed with HIV: A qualitative analysis of lived experiences of youth living with HIV in rural Rwanda.

Introduction: In sub-Saharan Africa, youth living with HIV, especially those who have lost one or both parents, face economic, socially and psychological challenges that hinder adherence to ART, ultimately leading to poor health outcomes. Partners In Health/Inshuti Mu Buzima implemented an Adolescent Support Group (ASG) to support HIV-positive youth aged 15-25 years. During the evaluation of the ASG program, we sought to better understand youths' lived experiences to improve our delivery of HIV care. Methods: We conducted qualitative in-depth, semi-structured individual interviews with youth enrolled in the ASG program. All interviews were conducted in-person or by telephone. Thematic analysis applying the framework approach with parallel inductive coding in Kinyarwanda and English was used. Results: We interviewed 35 youth who ranged in age from 16 to 29 years. The main themes related to the lived experiences of youth were (a) Experiences living with HIV, including disclosure, stigma, interactions with the health care system, and medication adherence; (b) external challenges, defined as challenges that were not related to the implementation of the ASG program; and (c) personal vision. Almost all youth reported acquiring HIV from their mothers and disclosure of HIV status occurred around the age of 10. Disclosure was often unintentional and followed by internalized and enacted stigma. Many reported poor past medication adherence which improved following enhanced counselling. External challenges were overwhelmingly economic in nature, and orphanhood was a root cause of other challenges such as difficulty accessing education, lack of transport to health facility, and lack of insurance fees. Despite these challenges, youth have an optimistic view of the future with dreams of health, economic attainment, marriage, and children. Conclusion: Healthcare providers should empower caregivers to support HIV disclosure. Supporting youth as they face many economic challenges could help address socio-economic barriers to good health and promote holistic well-being.

Implementation of Refugees' Inclusion in National Viral Hepatitis B and Hepatitis C Screening Campaign in Mahama Refugee Camp, Rwanda.

INTRODUCTION: The World Health Organization has called for the elimination of hepatitis B virus (HBV) and hepatitis C virus (HCV) as public health threats by 2030. In response to the United Nations High Commissioner for Refugees requests, Rwanda became the first country to include refugees in its national viral hepatitis prevention and management program in 2019. We used secondary data to describe the implementation of the first HBV and HCV screening program among refugees in Rwanda. METHODS: Rapid diagnostic tests were used to screen for HBV surface antigen (HBsAg) and HCV antibody (anti-HCV). We used routine data collected during the HBV and HCV mass screening campaign among Burundian refugees living in Mahama camp and program records to estimate the screening coverage, the prevalence of HBV and HCV, and the cost of the campaign. RESULTS: Over 28 days in February and March 2020, 26,498 unique individuals were screened for HBV and HCV, reflecting a screening coverage of 77.9% (95% confidence interval [CI]=76.5%, 78.4%). Coverage was greater than 90% among women aged 30-64 years, but younger age groups and men were less likely to be screened. On average, 946 clients were screened per day. The prevalence of anti-HCV was 1.1% (95% CI=1.0%, 1.3%), and the prevalence of HBsAg was 3.8% (95% CI=3.6%, 4.0%). We estimate that the total cost of the campaign was US$177,336.60, reflecting a per-person-screened cost of US$6.69. CONCLUSION: Conducting a mass screening was a feasible and effective strategy to achieve high screening coverage and identify refugees who were eligible for HBV and HCV treatment. This screening program in the Mahama refugee camp can serve as a reference for other refugee camps in Rwanda and elsewhere.

Knowledge among patients with Hepatitis C initiating on direct-acting antiviral treatment in rural Rwanda: A prospective cohort study.

BACKGROUND: Curative direct-acting antiviral treatment (DAA) has made it plausible to implement hepatitis C elimination interventions. However, poor hepatitis C knowledge among patients could impede the effectiveness of screening and treatment programs. OBJECTIVE: We assessed knowledge on hepatitis C among rural Rwandans initiating DAA treatment for hepatitis C in a prospective cohort. METHODS: We administered 15 true-false statements before treatment initiation and during one follow-up visit occurring either 1 or 2 months after treatment initiation. We assessed the average number of correct responses per patient, the proportion of correct responses to individual statements, pre-treatment predictors of knowledge, and whether post-initiation knowledge was associated with time since treatment initiation, quality of care, or adherence. RESULTS: Among 333 patients who answered knowledge questions before treatment initiation, 325 (97.6%) were re-assessed at a post-initiation visit. Pre-initiation, 72.1% knew hepatitis C was curable, 61.9% knew that hepatitis C could cause liver damage or cancer, and 42.3% knew that people with hepatitis C could look and feel fine. The average number of correct responses was 8.1 out of 15 (95% CI: 7.8-8.5), but was significantly lower among those with low educational attainment or with low literacy. Post-initiation, correct responses increased by an average of 2.0 statements (95% CI: 1.6, 2.4, p-value <0.001). Many patients still mistakenly believed that hepatitis C could be transmitted through kissing (66.5%), eating utensils (44.1%), handshakes (34.8%), and hugs (34.8%). Post-initiation knowledge is inversely associated with self-reported quality of care and unassociated with self-reported adherence. CONCLUSION: Although knowledge improved over time, key gaps persisted among patients. Accessible public education campaigns targeted to low-literacy populations emphasizing that hepatitis C can be asymptomatic, has severe consequences, and is curable could promote participation in mass screening campaigns and linkage to care. Visual tools could facilitate clinician-provided patient education.

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.

Prevalence of transmitted HIV-1 drug resistance among young adults attending HIV counselling and testing clinics in Kigali, Rwanda.

BACKGROUND: Scaling-up antiretroviral therapy (ART) in resource-limited settings has raised concerns of emerging HIV drug resistance (DR) and its transmission to newly infected individuals. To assess the prevalence of transmitted drug resistance (TDR) in recently HIV-infected individuals, a WHO TDR threshold survey was conducted among young adults in Kigali, Rwanda. METHODS: Between May and July 2011, HIV subtype and genotyping were performed on dried blood spots (DBS) prepared from blood specimens collected from newly HIV-diagnosed and ART-naive individuals aged 15 to 21 years in eight HIV voluntary counselling and testing (VCT) sites in Kigali. RESULTS: In total, 57 of the 68 DBS collected from eligible participants were successfully amplified. The median age of participants was 20 years and 86% were female. Most participants (96%) were infected with subtype A1 virus. Two participants (4%) had the K103N non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation and one (2%) had the M46L protease inhibitor (PI) mutation. The TDR prevalence was 3.5% (95% CI 0.4, 12.1) for NNRTI and 1.8% (95% CI 0.0, 9.4) for PI. CONCLUSIONS: The prevalence of HIV TDR in VCT attendees in Kigali was characterized as low (<5%) for all drug classes according to the WHO HIV DR threshold survey methodology. Despite a decade of widespread ART in Rwanda, TDR prevalence remains low, and so the current first-line ART regimens should continue to be effective. However, as scale-up of ART continues, frequent HIV DR surveillance is needed to monitor the effectiveness of available ART regimens at the population level.

HIV drug resistance mutations among patients failing second-line antiretroviral therapy in Rwanda.

BACKGROUND: Studies of patients failing second-line antiretroviral therapy (ART) in resource-limited settings (RLS) are few. Evidence suggests most patients who appear to be virologically failing do so not due to drug resistance but to poor adherence, which, if properly addressed, could allow continued use of less expensive first- and second-line regimens. Drug resistant mutations (DRMs) were characterized among patients virologically failing second-line ART in Rwanda. METHODS: A total of 128 adult patients receiving second-line ART for at least 6 months were invited to participate; 74 agreed and had HIV-1 viral load (VL) measured. Resistance genotypes were conducted in patients with virological failure (VF; that is, VL ≥1,000 copies/ml). RESULTS: In total, 35 patients met the criteria for VF. The median time on lopinavir/ritonavir-based second-line ART was 2.7 years. Of 30 successful resistance genotype analyses, 13 (43%) had ≥1 nucleoside reverse transcriptase inhibitor (NRTI) mutation, 18 (60%) had at least 1 non-NRTI mutation and 5 (17%) had at least 1 major protease inhibitor mutation. Eleven (37%) had virus without significant mutations that would be fully sensitive to first-line ART; 12 (40%) had DRM to first-line ART but sensitive to second-line ART. Only 7 patients (23%) demonstrated a DRM profile requiring third-line ART. CONCLUSIONS: Among 30 genotyped samples of patients with VF on second-line ART, more than one-third had no significant DRMs, implicating poor adherence as the primary cause of VF. The majority of patients (77%) would not have required third-line ART. These findings reinforce the need for intensive adherence assessment and counselling for patients who appear to be failing second-line ART in RLS.