The feasibility and acceptability of integrating hepatitis C and HIV diagnostic testing on centralized molecular laboratory platforms in Myanmar.

BACKGROUND: In Myanmar, 1.3 million people have been exposed to hepatitis C (HCV). However, public sector access to viral load (VL) testing for HCV diagnosis remains limited; ten near-point-of-care (POC) devices are available nationally. Myanmar's National Health Laboratory (NHL) has surplus capacity on centralized molecular testing platforms used for HIV diagnostics, presenting an opportunity for integrating HCV testing to expand overall testing capacity. This pilot assessed the operational feasibility and acceptability of HCV/HIV integrated testing implemented with a comprehensive package of supportive interventions. METHODS: HCV VL samples were collected prospectively from consenting participants at five treatment clinics and tested at Myanmar's NHL (October 2019-February 2020) on the Abbott m2000. To optimize integration, laboratory human resources were bolstered, staff trainings were offered, and existing laboratory equipment was serviced/repaired as needed. Diagnostics data during the intervention period were compared against HIV diagnostics data in the seven months prior. We conducted three time and motion analyses at the laboratory and semi-structured interviews with laboratory staff to assess time needs and program acceptability. RESULTS: 715 HCV samples were processed during the intervention period with an average test processing time of 18 days (IQR: 8-28). Despite adding HCV testing, average monthly test volumes were 2,331 for HIV VL and 232 for early infant diagnosis (EID), comparable to the pre-intervention period. Processing times were 7 days for HIV VL and 17 days for EID, also comparable to the pre-intervention period. HCV test error rate was 4.3%. Platforms utilization increased from 18.4% to 24.6%. All staff interviewed were supportive of HCV and HIV diagnostics integration; suggestions were made for broader implementation and expansion. CONCLUSIONS: With a package of supportive interventions, integration of HCV and HIV diagnostics on a centralized platform was operationally feasible, did not adversely impact HIV testing, and was acceptable to laboratory staff. In Myanmar, integrated HCV VL diagnostic testing on centralized platforms may be an important addition to existing near-POC testing in expanding national testing capacity for HCV elimination.

Epidemiological characteristics and real-world treatment outcomes of hepatitis C among HIV/HCV co-infected patients in Myanmar: A prospective cohort study.

Background and Aims: In Myanmar, public sector treatment programs for hepatitis C virus (HCV) infection were nonexistent until June 2017. WHO highlights the importance of simplification of HCV service delivery through task-shifting among health workers and decentralization to the primary health care level. Between November 2016 and November 2017, a study was conducted to describe the epidemiological data and real-world outcomes of treating HIV/HCV coinfected patients with generic direct acting antiviral (DAA) based regimens in the three HIV clinics run by nonspecialist medical doctors in Myanmar. Methods: HCV co-infection among people living with HIV (PLHIV) from two clinics in Yangon city and one clinic in Dawei city was screened by rapid diagnostic tests and confirmed by testing for viral RNA. Nonspecialist medical doctors prescribed sofosbuvir and daclatasvir based regimens (with or without ribavirin) for 12 or 24 weeks based on the HCV genotype and liver fibrosis status. Sustained virologic response at 12 weeks after treatment (SVR12) was assessed to determine cure. Results: About 6.5% (1417/21,777) of PLHIV were co-infected with HCV. Of 864 patients enrolled in the study, 50.8% reported history of substance use, 27% history of invasive medical procedures and 25.6% history of incarceration. Data on treatment outcomes were collected from 267 patients of which 257 (96.3%) achieved SVR12, 7 (2.6%) failed treatment, 2 (0.7%) died and 1 (0.4%) became loss to follow-up. Conclusion: The study results support the integration of hepatitis C diagnosis and treatment with DAA-based regimens into existing HIV clinics run by nonspecialist medical doctors in a resource-limited setting. Epidemiological data on HIV/HCV co-infection call for comprehensive HCV care services among key populations like drug users and prisoners in Yangon and Dawei.

Patient outcomes in public sector hepatitis C treatment programmes: a retrospective cohort analysis across five low- and middle-income countries.

OBJECTIVES: Given limited data on factors associated with hepatitis C virus (HCV) treatment discontinuation and failure in low- and middle-income countries, we aimed to describe patient populations treated for HCV in five countries and identify patient groups that may need additional support. DESIGN: Retrospective cohort analysis using routinely collected data. SETTING: Public sector HCV treatment programmes in India (Punjab), Indonesia, Myanmar, Nigeria (Nasarawa) and Vietnam. PARTICIPANTS: 104 957 patients who initiated treatment in 2016-2022 (89% from Punjab). PRIMARY OUTCOMES: Treatment completion and cure. RESULTS: Patient characteristics and factors associated with outcomes varied across countries and facilities. Across all patients, median age was 40 years (IQR: 29-52), 30.6% were female, 7.0% reported a history of injecting drugs, 18.2% were cirrhotic and 4.9% were coinfected with HIV. 79.8% were prescribed sofosbuvir+daclastasvir. Of patients with adequate follow-up, 90.6% (89,551) completed treatment. 77.5% (69,426) of those who completed treatment also completed sustained virological testing at 12 weeks (SVR12), and of those, 92.6% (64 305) were cured. In multivariable-adjusted models, in most countries, significantly lower treatment completion was observed among patients on 24-week regimens (vs 12-week regimens) and those initiated in later years of the programme. In several countries, males, younger patients <20 years and certain groups of cirrhotic patients were less likely to complete treatment or be cured. In Punjab, treatment completion was also lower in those with a family history of HCV and people who inject drugs (PWID); in other countries, outcomes were comparable for PWID. CONCLUSION: High proportions of patients completed treatment and were cured across patient groups and countries. SVR12 follow-up could be strengthened. Males, younger people and those with decompensated cirrhosis on longer regimens may require additional support to complete treatment and achieve cure. Adequate programme financing, minimal user fees and implementation of evidence-based policies will be critical to close gaps.

Feasibility of decentralised, task-shifted hepatitis C testing and treatment services in urban Myanmar: implications for scale-up.

OBJECTIVES: To assess the feasibility considerations for a decentralised, one-stop-shop model of care implemented in Yangon, Myanmar. SETTING: Two primary care level clinics in urban Yangon, Myanmar. DESIGN: This is a feasibility study of a highly effective care model. Using Intervention Complexity Framework by Gericke et al, we collated and analysed programmatic data and evaluation data to outline key project implementation requirements and experiences. PARTICIPANTS: Programmatic data were collected from clinical records, GeneXpert device test and maintenance reports, national guidelines, product and device instructions and site monitoring visit reports. Healthcare providers involved in delivering care model contributed interview data. RESULTS: The main feasibility considerations are appropriate storage for test kits and treatments (in response to temperature and humidity requirements), installation of a continuous stable electricity supply for the GeneXpert device, air-conditioning for the laboratory room hosting GeneXpert, access to a laboratory for pretreatment assessments and clear referral pathways for specialist consultation when required. Lessons from our project implementation experiences included the extensive time requirements for patient education, the importance of regular error monitoring and stock storage reviews and that flexible appointment scheduling and robust reminder system likely contributed to high retention in care. CONCLUSIONS: Detailed documentation and dissemination of feasibility requirements and implementation considerations is vital to assist others to successfully implement a similar model of care elsewhere. We provide 10 recommendations for successful implementation. TRIAL REGISTRATION NUMBER: The trial was registered at ClinicalTrials.gov NCT03939013 on May 6, 2019. This manuscript presents post-results data on feasibility.

Hepatitis C elimination in Myanmar: Modelling the impact, cost, cost-effectiveness and economic benefits.

BACKGROUND: Myanmar has set national hepatitis C (HCV) targets to achieve 50% of people diagnosed and 50% treated by 2030. The WHO has additional targets of reducing incidence by 80% and mortality by 65% by 2030. We aimed to estimate the impact, cost, cost-effectiveness and net economic benefit of achieving these targets. METHODS: Mathematical models of HCV transmission, disease progression and the care cascade were calibrated to 15 administrative regions of Myanmar. Cost data were collected from a community testing and treatment program in Yangon. Three scenarios were projected for 2020-2030: (1) baseline (current levels of testing/treatment); and testing/treatment scaled up sufficiently to reach (2) the national strategy targets; and (3) the WHO targets. FINDINGS: Without treatment scale-up, 333,000 new HCV infections and 97,000 HCV-related deaths were estimated to occur in Myanmar 2020-2030, with HCV costing a total $100 million in direct costs (testing, treatment, disease management) and $10.4 billion in lost productivity. In the model, treating 55,000 people each year was sufficient to reach the national strategy targets and prevented a cumulative 40,000 new infections (12%) and 25,000 HCV-related deaths (25%) 2020-2030. This was estimated to cost a total $189 million in direct costs ($243 per DALY averted compared to no treatment scale-up), but only $9.8 billion in lost productivity, making it cost-saving from a societal perspective by 2024 with an estimated net economic benefit of $553 million by 2030. Reaching the WHO targets required further treatment scale-up and additional direct costs but resulted in greater longer-term benefits. INTERPRETATION: Current levels of HCV testing and treatment in Myanmar are insufficient to reach the national strategy targets. Scaling up HCV testing and treatment in Myanmar to reach the national strategy targets is estimated to generate significant health and economic benefits. FUNDING: Gilead Sciences.

Initial success from a public health approach to hepatitis C testing, treatment and cure in seven countries: the road to elimination.

With political will, modest financial investment and effective technical assistance, public sector hepatitis C virus (HCV) programmes can be established in low- and middle-income countries as a first step towards elimination. Seven countries, with support from the Clinton Health Access Initiative (CHAI) and partners, have expanded access to HCV treatment by combining programme simplification with market shaping to reduce commodity prices. CHAI has supported a multipronged approach to HCV programme launch in Cambodia, India, Indonesia, Myanmar, Nigeria, Rwanda and Vietnam including pricing negotiations with suppliers, policy development, fast-track registrations of quality-assured generics, financing advocacy and strengthened service delivery. Governments are leading programme implementation, leveraging HIV programme infrastructure/financing and focusing on higher-HCV prevalence populations like people living with HIV, people who inject drugs and prisoners. This manuscript aims to describe programme structure and strategies, highlight current commodity costs and outline testing and treatment volumes across these countries. Across countries, commodity costs have fallen from >US$100 per diagnostic test and US$750-US$900 per 12-week pan-genotypic direct-acting antiviral regimen to as low as US$80 per-cure commodity package, including WHO-prequalified generic drugs (sofosbuvir + daclatasvir). As of December 2019, 5900+ healthcare workers were trained, 2 209 209 patients were screened, and 120 522 patients initiated treatment. The cure (SVR12) rate was >90%, including at lower-tier facilities. Programmes are successfully implementing simplified, decentralised public health approaches. Combined with political will and affordable pricing, these efforts can translate into commitments to achieve global targets. However, to achieve elimination, additional investment in scale-up is required.

Decentralized, Community-Based Hepatitis C Point-of-Care Testing and Direct-Acting Antiviral Treatment for People Who Inject Drugs and the General Population in Myanmar: Protocol for a Feasibility Study.

BACKGROUND: The advent of direct-acting antivirals (DAAs) and point-of-care (POC) testing platforms for hepatitis C allow for the decentralization of care to primary care settings. In many countries, access to DAAs is generally limited to tertiary hospitals, with limited published research documenting decentralized models of care in low-and middle-income settings. OBJECTIVE: This study aims to assess the feasibility, acceptability, effectiveness, and cost-effectiveness of decentralized community-based POC testing and DAA therapy for hepatitis C among people who inject drugs and the general population in Yangon, Myanmar. METHODS: Rapid diagnostic tests for anti-hepatitis C antibodies were carried out on-site and, if reactive, were followed by POC GeneXpert hepatitis C RNA polymerase chain reaction tests. External laboratory blood tests to exclude other major health issues were undertaken. Results were given to participants at their next appointment, with the participants commencing DAA therapy that day if a specialist review was not required. Standard clinical data were collected, and the participants completed behavioral questionnaires. The primary outcome measures are the proportion of participants receiving GeneXpert hepatitis C RNA test, the proportion of participants commencing DAA therapy, the proportion of participants completing DAA therapy, and the proportion of participants achieving sustained virological response 12 weeks after completing DAA therapy. RESULTS: Recruitment was completed on September 30, 2019. Monitoring visits and treatment outcome visits are scheduled to continue until June 2020. CONCLUSIONS: This feasibility study in Myanmar contributes to the evidence gap for community-based hepatitis C care in low- and middle-income settings. Evidence from this study will inform the scale-up of hepatitis C treatment programs in Myanmar and globally.