The advent of direct-acting antivirals (DAAs) has redefined the landscape of hepatitis C (HCV) treatment, offering unprecedented efficacy, safety, and patient tolerability. Since their introduction in 2014, DAAs have shifted the treatment paradigm from burdensome interferon-based regimens to highly effective, patient-friendly oral therapies. With sustained virologic response (SVR) rates of 95–99% and treatment durations as short as 8–12 weeks, DAAs have not only improved individual patient outcomes but also set the stage for global HCV eradication efforts. This overview explores the transformative impact of DAAs, their systemic implications, and lessons for market access and patient outcomes, providing insights for pharmaceutical executives navigating this evolving market.

Background
Hepatitis C, a viral infection affecting an estimated 130–150 million people globally, has historically been a major public health challenge, contributing to approximately 700,000 deaths annually due to liver-related complications. Prior to 2014, treatment relied on injectable interferon-based regimens. These intervention offered SVR rates of around 50%, required 24–72 weeks of therapy. In addition, it was associated with severe side effects (including chronic fatigue, depression, and anemia). These limitations led to low treatment adherence and significant patient warehousing, where individuals delayed therapy in anticipation of better options. The introduction of interferon-free DAAs marked a turning point, delivering near-cure rates, minimal side effects, and broader applicability across HCV genotypes, fundamentally altering the prognosis for patients and health systems.

Impact of DAAs: A Systems Perspective
From a systems perspective, DAAs have catalyzed a ripple effect across the HCV treatment ecosystem, influencing clinical, economic, and societal outcomes.

• Clinical Transformation: Clinical Transformation:
  DAAs shifted the focus from managing chronic HCV to achieving cures. This reduces the long-term burden of cirrhosis, liver cancer, and death. Early treatment, supported by strong clinical evidence, improves outcomes. It also prevents disease progression and aligns with proactive health system strategies.

• Economic Dynamics: The high initial costs of DAAs prompted health systems to impose restrictions. Patients with advanced disease were prioritized. However, as competition among DAA manufacturers increases, net prices are declining. This dynamic enables broader access. Health systems are now balancing upfront costs against long-term savings. Savings come specifically from reduced liver-related complications.

• Societal Impact: DAAs have highlighted the need for inclusive treatment strategies targeting at-risk populations, such as people who inject drugs or those with HIV co-infection. Innovative care models, such as telemedicine and pop-up clinics, are emerging to address screening and access gaps.

• Feedback Loops: The success of DAAs has driven demand for enhanced screening and diagnosis. This created a feedback loop where increased case identification fuel treatment uptake. The consequence is reduced transmission. However, barriers like stigma and limited healthcare infrastructure in high-risk populations require targeted interventions to sustain progress.
  This interconnected impact underscores the need for health systems to adopt holistic strategies.

Lessons for Market Access and Better Patient Outcomes

1. Strategic Market Access:

   • Leverage Competition: As new DAAs enter the market, pharmaceutical companies can negotiate discounts and rebates to improve payer acceptance. This approach can expand access to previously untreated populations.

   • Address Restrictions: Health systems in Europe and the U.S. initially restricted DAA access to patients with advanced disease. Advocacy for evidence-based policies that prioritize early treatment can improve outcomes and reduce long-term costs.

   • Tailored Positioning: Future DAAs should target niche markets, such as difficult-to-treat genotypes or treatment-experienced patients, to maintain market relevance in an eradication-focused landscape.

2. Enhancing Patient Outcomes:

   • Inclusive Treatment Models: Extending DAA therapy to marginalized groups, such as people who inject drugs, requires innovative delivery models like pop-up clinics and telemedicine, as well as education to prevent reinfection.

   • Screening and Diagnosis: Scaling up screening programs is critical to identifying undiagnosed cases, particularly in high-risk populations. Partnerships with community organizations can enhance outreach.

   • Long-Term Monitoring: Comprehensive follow-up mechanisms are essential to ensure treatment adherence and prevent reinfection, especially in populations with complex health needs.

Conclusion
Direct-acting antivirals have transformed hepatitis C treatment, offering a pathway to eradication through unparalleled efficacy and patient-centered care. Their systemic impact demands a dynamic approach to navigating market access and patient engagement. By leveraging competition, we can expand access to treatment. Advocating for targeted intervention ensures support for high-risk groups. Investing in screening and innovative care models improves early detection and access. Together, these actions drive sustained progress toward the WHO’s 2030 eradication goals. Ultimately improving patient outcomes and reshaping the global fight against HCV.