Resistance-Driven Treatment Failure: A Challenge to HCV Elimination in Pakistan
Author(s)
Saima Mushtaq, PhD1, Aaron G. Lim, DPhil2, Amjad Khan, PhD3, Yu Fang, PhD4.
1Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, 2Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom, 3Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan, 4Department of Pharmacy Administration and Clinical Pharmacy, Xi'an Jiaotong University, Xi'an, China.
1Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, 2Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom, 3Department of Pharmacy, Quaid-i-Azam University, Islamabad, Pakistan, 4Department of Pharmacy Administration and Clinical Pharmacy, Xi'an Jiaotong University, Xi'an, China.
OBJECTIVES: Hepatitis C virus (HCV) genotype 3 is the predominant strain in Pakistan and presents significant barriers to elimination efforts due to higher rates of treatment failure. Although direct-acting antiviral (DAA) therapies have improved cure rates, resistance-associated substitutions (RASs) in the NS5A region of HCV contribute significantly to these failures. The role of liver cirrhosis and GT3 subtypes (3a vs 3b) in shaping resistance patterns not fully understood. This study determines the prevalence and predictors of NS5A RASs among HCV GT3 DAA-failing patients and evaluates the influence of cirrhosis and viral subtype on resistance patterns.
METHODS: We conducted a multicenter retrospective analysis of 153 HCV GT3 patients with confirmed DAA treatment failure from tertiary hospitals across Pakistan (2022-2024). Data included cirrhosis status, viral subtype, and prior DAA exposure. NS5A RASs were identified by Sanger sequencing. RAS prevalence was compared across subgroups, and multivariate logistic regression was used to identify independent predictors.
RESULTS: Among 153 patients with treatment failure, 64% had cirrhosis. HCV subtype distribution included 107 (70%) patients with subtype 3a and 46 (30%) with subtype 3b. NS5A RASs were detected in 68.8% of cirrhotic patients compared to 31.2% of non-cirrhotic patients (p < 0.01). RAS prevalence was significantly higher in subtype 3b patients (82.6%, 38/46) versus subtype 3a patients (57.8%, 62/107) (p = 0.004). Patients treated with sofosbuvir/velpatasvir had a lower Y93H RAS rate (52%) than those treated with sofosbuvir/daclatasvir (73%). Multivariate logistic regression identified cirrhosis (OR: 2.8; 95% CI: 1.4-5.4) and subtype 3b infection (OR: 3.6; 95% CI: 1.8-7.1) as independent predictors of resistance.
CONCLUSIONS: Patients with cirrhosis and subtype 3b have a higher prevalence of NS5A RASs, which contribute to treatment failure. In real-world settings like Pakistan, the presence of these RASs poses challenges for retreatment, potentially leading to increased healthcare costs and delays in achieving national HCV elimination goals.
METHODS: We conducted a multicenter retrospective analysis of 153 HCV GT3 patients with confirmed DAA treatment failure from tertiary hospitals across Pakistan (2022-2024). Data included cirrhosis status, viral subtype, and prior DAA exposure. NS5A RASs were identified by Sanger sequencing. RAS prevalence was compared across subgroups, and multivariate logistic regression was used to identify independent predictors.
RESULTS: Among 153 patients with treatment failure, 64% had cirrhosis. HCV subtype distribution included 107 (70%) patients with subtype 3a and 46 (30%) with subtype 3b. NS5A RASs were detected in 68.8% of cirrhotic patients compared to 31.2% of non-cirrhotic patients (p < 0.01). RAS prevalence was significantly higher in subtype 3b patients (82.6%, 38/46) versus subtype 3a patients (57.8%, 62/107) (p = 0.004). Patients treated with sofosbuvir/velpatasvir had a lower Y93H RAS rate (52%) than those treated with sofosbuvir/daclatasvir (73%). Multivariate logistic regression identified cirrhosis (OR: 2.8; 95% CI: 1.4-5.4) and subtype 3b infection (OR: 3.6; 95% CI: 1.8-7.1) as independent predictors of resistance.
CONCLUSIONS: Patients with cirrhosis and subtype 3b have a higher prevalence of NS5A RASs, which contribute to treatment failure. In real-world settings like Pakistan, the presence of these RASs poses challenges for retreatment, potentially leading to increased healthcare costs and delays in achieving national HCV elimination goals.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO212
Topic
Clinical Outcomes, Epidemiology & Public Health, Real World Data & Information Systems
Topic Subcategory
Clinical Outcomes Assessment, Comparative Effectiveness or Efficacy
Disease
Gastrointestinal Disorders, Generics, Infectious Disease (non-vaccine), Oncology