1. Implementing programs on diagnosis and treatment of hepatitis C in lower- and middle-income countries: What can we learn from the HIV experience? July 2014 Colleen Connell, Clinton Health Access Initiative

2. The opportunities and barriers faced by HCV are similar to those faced by HIV in early days of global response Current status Lack of HCV treatment programs in lower and middle-income countries is leading to high mortality, high costs to the public health system, and continued transmission Market shifts Development of new HCV treatments that greatly increase chance of curing disease Release of first WHO guidelines for HCV diagnosis and treatment Push for greater global access to treatment by advocacy community Potential barriers Prohibitive prices for necessary drugs and diagnostics Perceived complexity of diagnostic algorithms and treatment regimens Lack of country-level diagnostic and treatment guidelines and programs Lack of infrastructure for treatment and diagnosis Difficulties in case-finding due to perceived stigma of disease Sources: WHO(1), UNITAID(1), TAG(1) 2

3. However, there are important differences between HIV and HCV that must be considered when adapting HIV lessons Drugs suppress virus Effect of drugs Chronic disease management is not necessary for HCV Location of burden Over 80% in low/lower middle-income countries Price reductions will be key as donor interest in middle-income markets may be limited Economic impact Affecting people in their prime, high direct economic loss Strong evidence of potential impact in morbidity/mortality is needed to justify national programs Drugs cure patients ~ 80% in middle- income countries Later stage mortality, less direct economic loss Donor priority Donors open to large-scale treatment programs Need to focus on highly cost- effective interventions from the beginning Donor support for large-scale programs unlikely 3 Lessons from HIV must be tailored to HCV – adapted rather than copied HIVHCVIMPLICATION

4. Seven key lessons from the HIV experience can guide future HCV program development and scale up Support operational technical assistance (TA) to accelerate guideline adoption, implementation and updating Ensure diagnostic programs and products develop in parallel with treatment Coordinate and align activities to leverage existing infrastructure Promote the rational deployment of diagnostic equipment Encourage the availability of a regulatory pathway for generic drugs and diagnostics Emphasize price reduction to drive greater access Build national, large-scale access programs early on 1 2 3 4 5 6 7 4

5. 5 HIV: history and context Normative guidelines from WHO were a key factor accelerating HIV treatment scale-up and impact Operational barriers (particularly around planning, HR, and budgeting) often delayed the adoption, implementation, and updating of guidelines at the country level Due to delays, impact of treatment innovations lagged in many countries TA to MOHs was effective in mitigating operational barriers HCV: how to apply Key lesson Support operational TA to accelerate guideline adoption, implementation, and updating Provide TA to adapt WHO guidelines to country context Support program operational planning - including systems, HR, budgeting and training activities - to drive guidelines implementation Establish process for rapidly updating local guidelines and programs (especially as new products come to market) Operational TA is key to adapting guidelines at the country level and ensuring that systems are in place to implement them Sources: NIH (1), WHO (1, 2), CHAI interviews, World Bank (1) 1

6. 6 HIV: history and context Guidance and TA for lab systems often lagged behind HIV treatment guidance Delayed emphasis on laboratory system strengthening (e.g., training, QA/QC, and sample transport) was a bottleneck to treatment uptake Similarly, innovation in diagnostic products (such as POC platforms) lagged treatment Investment in diagnostic innovation is just now becoming a priority HCV: how to apply Key lesson 2 Ensure diagnostic programs and products develop in parallel with treatment Provide TA for lab system strengthening early on Promote investment in diagnostic innovations (e.g., HCV antigen RDTs and DBS VL) as well as guidance where needed (e.g. target product profiles) in order to keep pace with advances in treatment Diagnostic programs require investment in systems strengthening and innovation Sources: NIH (1), Fearson (1), Chappel (1), CHAI interviews

7. 7 HIV: history and context International cooperation accelerated best practice sharing between countries Eventual coordination of partner activities led to more efficient resource utilization (note coordination had to be learned over time) Establishment of vertical HIV programs allowed for rapid scale-up of services, but these now must be integrated into the broader health system HCV: how to apply Key lesson 3 Coordinate and align activities to leverage existing infrastructure Share information between countries implementing HCV programs to encourage efficiency Develop a global body similar to UNAIDS in the HCV space to lead partner activities Integrate HCV programs into existing health systems where possible (carefully consider the downsides of siloing) Strong coordination among partners can make programs more cost-effective and sustainable Sources: Garrett (1), Howard (1), Berkman (1), Boyer (1), Rabkin (1), Ford (1)

8. 8 HIV: history and context Efficient placement of diagnostic equipment, particularly testing platforms, is a longstanding challenge for partners working in HIV Equipment purchasing often preceded the establishment of national lab strategies in many countries Lack of robust supply chain and maintenance schemes has led to significant equipment downtime and underutilization HCV: how to apply Key lesson 4 Promote the rational deployment of diagnostic equipment Survey existing infrastructure and identify potential synergies prior to purchasing/placing new diagnostic equipment Define national strategic plans for diagnostic deployment and maintenance prior to program launch The efficient placement of diagnostic equipment can reduce program costs and improve effectiveness Sources: CHAI interviews, WHO(1), Olmsted(1), Parsons(1)

9. 9 HIV: history and context The WHO established prequalification in 2001, creating a validated pathway for generic ARVs to enter the market A mechanism for non-US market ARVs to be approved by the FDA was established in 2004 for purchase by PEPFAR For HIV diagnostics, an unclear regulatory pathway led to delays and duplication of efforts until a diagnostics PQ process was established in 2008 – note that even with PQ country registration a frequent bottleneck HCV: how to apply Key lesson 5 Encourage the availability of a regulatory pathway for generic drugs and diagnostics Establish a funded PQ process for fast and internationally accepted quality assurance of generic HCV treatments Ensure that a clear venue for the rapid validation and regulatory approval of new diagnostic tools also exists in order to encourage investment and innovation Rapid regulatory pathways can accelerate the availability of necessary drugs and diagnostics Sources: Scielo (1), UNICEF (1), CHAI interviews

10. 10 HIV: history and context Community activists created pressure on ARV prices ARV prices declined dramatically through a number of strategies: New supplier entry and increased competition Increased market transparency and pooled procurement Cost-based negotiations based on reduced production costs HCV: how to apply Key lesson 6 Emphasize price reduction to drive greater access Encourage increased generic competition through greater transparency and reduced barriers to entry Pursue cost-based negotiations, building on process chemistry and sourcing cost reductions Use pooled procurement and other volume-based negotiation strategies Price reductions can catalyze patient access by removing price as a barrier Sources: CHAI interviews

11. 11 HIV: history and context A focus on national roll-outs built momentum and buy-in Universal access, focusing on multiple entry points, accelerated uptake Decentralized HIV care increased coverage and improved early access to care Demand generation activities, such as community support in education and screening, were necessary to drive uptake HCV: how to apply Key lesson 7 Build national, large-scale access programs early on Prioritize establishing nation-wide programs with rapid scale-up Provide access to HCV treatment through multiple, decentralized channels to accelerate uptake Generate demand through community engagement to ensure that access programs reach scale A focus on achieving large patient volumes early on can accelerate the development of access programs Sources: Rueda (1), Howard (1), Berkman (1), Boyer (1) Ford (1)

12. Practical operational research can support the application of HIV lessons to HCV 12 In order to maximize it’s contribution to increasing access in HCV, research should:..consider the operational challenges that the roll out of new ideas will entail..build upon existing best practices..focus on regimen and dose optimization for the widest possible population to support volume optimization..take into account the minimum resources needed, rather than the optimal..concentrate on large operational programs as scale is often the limiting success factor in practice