Nurse-led initiation of hepatitis C care in rural Cambodia.

Objective: To determine whether a nurse-led model of care for patients with hepatitis C virus (HCV) infections can provide safe and effective diagnosis and treatment in a resource-poor setting in rural Cambodia. Methods: The nurse-led initiation pilot project was implemented by Médecins Sans Frontières in collaboration with the Cambodian health ministry in two operational districts in Battambang Province between 1 June and 30 September 2020. Nursing staff at 27 rural health centres were trained to identify signs of decompensated liver cirrhosis and to provide HCV treatment. Patients without decompensated cirrhosis or another comorbidity were initiated at health centres onto combined treatment with sofosbuvir, 400 mg/day, and daclatasvir, 60 mg/day, orally for 12 weeks. Treatment adherence and effectiveness were assessed during follow-up. Findings: Of 10 960 individuals screened, 547 had HCV viraemia (i.e. viral load ≥ 1000 IU/mL). Of the 547, 329 were eligible for treatment initiation at health centres through the pilot project. All 329 (100%) completed treatment and 310 (94%; 95% confidence interval: 91-96) achieved a sustained virological response 12 weeks post-treatment. Depending on patient subgroups, this response varied from 89% to 100%. Only two adverse events were recorded; both were determined as unrelated to treatment. Conclusion: The safety and effectiveness of direct-acting antiviral medication has previously been demonstrated. Models of HCV care now need to enable greater access for patients. The nurse-led initiation pilot project provides a model for use in other resource-poor settings to scale up national programmes.

Costing analysis of field implementation of hepatitis C case detection in rural Maung Russey operational district, Cambodia.

BACKGROUND: When a new health programme is introduced, it is crucial to estimate the costs for rational health policy decision-making. The aim of this study was to determine the costs of implementing two strategies for hepatitis C virus (HCV) screening in rural Cambodia. METHODS: We retrospectively analysed clinical and cost data that were collected routinely for a demonstration project for scaling up HCV screening and testing in Cambodia. The programme data were collected between March and December 2018 in Maung Russey operational district in Battambang Province, Cambodia. FINDINGS: During the study period, 24 230 people were screened; 1194 (5%) were HCV seropositive, of whom 793 (66%) were confirmed to be viraemic. During the study period, 18% of the estimated population of the operational district were screened, of whom 45% were estimated to be seropositive and 41% to be viraemic. With passive screening alone, 8% of the estimated population were screened, of whom 29% were estimated to be seropositive and 28% viraemic. The cost per detected viraemic case was US$ 194 for passive screening alone and US$ 283 for passive and active screening combined. Labour costs (31%) and tests and materials (29%) comprised the largest proportions of the cost. CONCLUSION: Combined active and passive screening per viraemic case detected was US$ 89 more expensive than passive screening alone but provided a higher yield (41% versus 28%) of viraemic cases. Therefore, adding active screening to passive screening is beneficial. Selective active screening strategies, such as targeting people over 45 years and other higher-risk groups, added value for HCV diagnosis.

Decentralised hepatitis C testing and treatment in rural Cambodia: evaluation of a simplified service model integrated in an existing public health system.

BACKGROUND: Direct-acting antiviral treatment for hepatitis C virus (HCV) has provided the opportunity for simplified models of care delivered in decentralised settings by non-specialist clinical personnel. However, in low-income and middle-income countries, increasing overall access to HCV care remains an ongoing issue, particularly for populations outside of urban centres. We therefore aimed to implement a simplified model of HCV care via decentralised health services within a rural health operational district in Battambang province, Cambodia. METHODS: The study cohort included adult residents (≥18 years) of the health operational district of Moung Russei who were voluntarily screened at 13 local health centres. Serology testing was done by a rapid diagnostic test using SD Bioline HCV (SD Bioline HCV, Standard Diagnostics, South Korea) with capillary blood. HCV viral load testing was done by GeneXpert (Cepheid, Sunnyvale, CA, USA). Viraemic patients (HCV viral load ≥10 IU/mL) received pretreatment assessment by a general physician and minimal treatment evaluation tests at the health operational district referral hospital. Viraemic patients who did not have additional complications received all HCV care follow-up at the local health centres, provided by nursing staff, and patients who had decompensated cirrhosis, previously treated with a direct-acting antiviral, HBV co-infection, or other comorbidities requiring observation continued receiving care at the referral hospital with a general physician. Patients deemed eligible for treatment were prescribed oral sofosbuvir (400 mg) and daclatasvir (60 mg) once a day for 12 weeks, or 24 weeks for patients with decompensated cirrhosis or those previously treated with a direct-acting antiviral. HCV cure was defined as sustained virological response at 12 weeks after treatment (HCV viral load <10 IU/mL). Patients were assessed for serious and non-serious adverse events at any time between treatment initiation and 12 weeks post-treatment testing. FINDINGS: Between March 12, 2018, and Jan 18, 2019, 10 425 residents (ie, 7·6% of the estimated 136 571 adults in the health operational district of Moung Russei) were screened. Of those patients screened, the median age was 44 years (IQR 31-55) and 778 (7·5%) were HCV-antibody positive. 761 (97·8%) of 778 antibody-positive patients received HCV viral load testing, and 540 (71·0%) of those tested were HCV viraemic. Among these 540 patients, linkage to treatment and follow-up care was high, with 533 (98·7%) attending a baseline consultation at the HCV clinic, of whom 530 (99·4%) initiated treatment. 485 (91·5%) of 530 patients who initiated treatment received follow-up at a health centre and 45 (8·5%) were followed up at the referral hospital. Of the 530 patients who initiated direct-acting antiviral therapy, 515 (97·2%) completed treatment. Subsequently, 466 (90·5%) of 515 patients completed follow-up, and 459 (98·5%) of 466 achieved a sustained virological response at 12 weeks after treatment. Two (0·4%) adverse events (fatigue [n=1] and stomach upset [n=1]) and five (0·9%) serious adverse events (infection [n=2], cardiovascular disease [n=1], and panic attack [n=1], with data missing for one of the causes of serious adverse events) were reported among patients who initiated treatment. All serious adverse events were deemed to be unrelated to therapy. INTERPRETATION: This pilot project showed that a highly simplified, decentralised model of HCV care can be integrated within a rural public health system in a low-income or middle-income country, while maintaining high patient retention, treatment efficacy, and safety. The project delivered care via accessible, decentralised primary health centres, using non-specialist clinical staff, thereby enhancing the efficient use of limited resources and maximising the potential to test and treat individuals living with HCV infection. FUNDING: Médecins Sans Frontières.

Cost and cost-effectiveness of a simplified treatment model with direct-acting antivirals for chronic hepatitis C in Cambodia.

BACKGROUND & AIMS: In 2016, Médecins Sans Frontières established the first general population Hepatitis C virus (HCV) screening and treatment site in Cambodia, offering free direct-acting antiviral (DAA) treatment. This study analysed the cost-effectiveness of this intervention. METHODS: Costs, quality adjusted life years (QALYs) and cost-effectiveness of the intervention were projected with a Markov model over a lifetime horizon, discounted at 3%/year. Patient-level resource-use and outcome data, treatment costs, costs of HCV-related healthcare and EQ-5D-5L health states were collected from an observational cohort study evaluating the effectiveness of DAA treatment under full and simplified models of care compared to no treatment; other model parameters were derived from literature. Incremental cost-effectiveness ratios (cost/QALY gained) were compared to an opportunity cost-based willingness-to-pay threshold for Cambodia ($248/QALY). RESULTS: The total cost of testing and treatment per patient for the full model of care was $925(IQR $668-1631), reducing to $376(IQR $344-422) for the simplified model of care. EQ-5D-5L values varied by fibrosis stage: decompensated cirrhosis had the lowest value, values increased during and following treatment. The simplified model of care was cost saving compared to no treatment, while the full model of care, although cost-effective compared to no treatment ($187/QALY), cost an additional $14 485/QALY compared to the simplified model, above the willingness-to-pay threshold for Cambodia. This result is robust to variation in parameters. CONCLUSIONS: The simplified model of care was cost saving compared to no treatment, emphasizing the importance of simplifying pathways of care for improving access to HCV treatment in low-resource settings.

High sustained viral response rate in patients with hepatitis C using generic sofosbuvir and daclatasvir in Phnom Penh, Cambodia.

Safe and efficacious pan-genotypic direct-acting antiviral (DAA) regimens, such as sofosbuvir and daclatasvir (SOF + DCV), facilitate simplified models of care for hepatitis C virus (HCV). However, in Cambodia access to HCV testing and treatment has typically been low. In response, Médecins Sans Frontières (MSF) implemented a HCV testing and treatment pilot project in Phnom Penh, Cambodia in 2016. This project provides the first real-world evidence of SOF + DCV effectiveness across a large patient cohort using a simplified care model in Cambodia. Patients treated with SOF + DCV from September 2016 to June 2019 were included in the analysis. Medical standard operational procedures (SOPs) were simplified significantly across the study period. Treatment effectiveness was assessed by sustained viral response at 12 weeks post-treatment (SVR12) according to a modified intention-to-treat methodology. Treatment safety was assessed by clinical outcome and occurrence of serious and nonserious adverse events (S/AE). Of 9158 patients, median age was 57 years and 39.6% were male. At baseline assessment, 27.2% of patients had compensated cirrhosis and 2.9% had decompensated cirrhosis. Genotype 6 was predominant (53.0%). Among patients analysed according to modified intention to treat (n = 8525), treatment effectiveness was high, with 97.2% of patients achieving SVR12. Occurrence of SAE was low (0.7%). Treatment effectiveness and safety was not affected by the iterative simplification to treatment modality. In conclusion, in this large treatment cohort in Phnom Penh, Cambodia, the SOF + DCV regimen showed high rates of treatment effectiveness and safety across patient sub-groups and during progressive simplification.

Molecular epidemiology of hepatitis C virus in Cambodia during 2016-2017.

In Cambodia, little epidemiological data of hepatitis C virus (HCV) is available. All previous studies were limited to only small or specific populations. In the present study, we performed a characterization of HCV genetic diversity based on demography, clinical data, and phylogenetic analysis of HCV non-structural 5B (NS5B) sequences belonging to a large cohort of patients (n = 3,133) coming from majority part of Cambodia between September 2016 and December 2017. The phylogenetic analysis revealed that HCV genotype 1 and 6 were the most predominant and sharing equal proportions (46%). The remaining genotypes were genotype 2 (4.3%) and unclassified variants (3.6%). Among genotype 1, subtype 1b was the most prevalent subtype accounting for 94%. Within genotype 6, we observed a high degree of diversity and the most common viral subtypes were 6e (44%) and 6r (23%). This characteristic points to the longstanding history of HCV in Cambodia. Geographic specificity of viral genotype was not observed. Risks of HCV infection were mainly associated with experience of an invasive medical procedure (64.7%), having partner with HCV (19.5%), and blood transfusion (9.9%). In addition, all of these factors were comparable among different HCV genotypes. All these features define the specificity of HCV epidemiology in Cambodia.

Demonstration of the diagnostic agreement of capillary and venous blood samples, using hepatitis-C virus SD Bioline© rapid test: A clinic-based study.

BACKGROUND: Simplifying hepatitis C virus (HCV) screening is a key step in achieving the elimination of HCV as a global public health threat by 2030. OBJECTIVES: The objective of this study was to demonstrate the agreement of capillary blood and venipuncture specimens when using SD Bioline© HCV, a low-cost rapid diagnostic test (RDT), prequalified by WHO in 2016 on venous blood samples. STUDY DESIGN: Recruitment was conducted prospectively among adult patients presenting for HCV testing at the Médecins Sans Frontières (MSF) clinic of Preah Kossamak Hospital (Phnom Penh, Cambodia) between October and November 2017. Capillary and venous blood samples were collected from consenting patients and tested with SD Bioline© HCV. Two independent, blinded readers, and in the case of disagreement, a third reader, interpreted the results of each blood sample. Concordance between results was compared using Cohen's Kappa interrater reliability statistic. Discrepant sample pairs were tested with an enzyme immunoassay, the reference standard, at the Institute Pasteur of Cambodia. RESULTS: Among 421 pairs of samples collected, reader disagreement occurred for 0.7% (n = 3) of the participants. Sixty-four percent of capillary and venous blood sample pairs tested positive for HCV, with a Kappa statistic of 0.985 between the two methods. Three participants with discrepant sample pair results tested positive with EIA. CONCLUSIONS: Capillary and venous blood samples were concordant when tested with HCV SD Bioline© in a clinical context. This simplified testing approach is essential to the scale-up of HCV screening and useful in resource-limited settings or among populations for whom venipuncture is problematic.

Vital status of pre-ART and ART patients defaulting from care in rural Malawi.

OBJECTIVES: To ascertain the outcome of pre-Antiretroviral therapy (ART) and ART patients defaulting from care and investigate reasons for defaulting. METHODS: Patients defaulting from HIV care in Chiradzulu between July 2004 and September 2007 were traced at last known home address. Deaths and moves were recorded, and patients found alive were interviewed. Defaulting was defined as missed last appointment by more than 1 month among patients of unknown vital status. RESULTS: A total of 1637 individuals were traced (54%-88% of eligible), 981 pre-ART and 656 ART patients. Of 694 pre-ART patients found, 49% had died (51% of adults and 38% of children), a median of 47 days after defaulting, and 14% had moved away. Of 451 ART patients found, 54% had died (54% of adults and 50% of children), a median of 52 days after defaulting, and 20% had moved away. Overall, 221 patients were interviewed (90% of those found alive), 42% had worked outside the district in the previous year; 49% of pre-ART and 19% of ART patients had not disclosed their HIV status to other household members. Main reasons for defaulting were stigma (43%), care dissatisfaction (34%), improved health (28%) and for ART discontinuation, poor understanding of disease or treatment (56%) and drug side effects (42%). CONCLUSION: This study in a rural African HIV programme reveals the dynamics related to health service access and use, and it provides information to correct programme mortality estimates for adults and children.