Molecular characteristics of hepatitis C genotype 2 in Georgia and its implication on DAA treatment outcomes within national hepatitis C elimination program
Project Status: 3 Approved without Funding
Duration in months: 24 months
Objective
Georgia has one of the highest HCV prevalence rates in the world. In partnership with the US CDC, and commitment from Gilead Sciences to donate DAAs, initially sofosbuvir, the country embarked on the world’s first hepatitis C elimination program in April, 2015. The overall goal of this program is to eliminate HCV in the country through identifying and treating all HCV patients strengthened by effective prevention interventions toward zero new infections. Georgia has set itself the ambitious target of diagnosing 90% of people living with HCV by 2020, treating 95% of those diagnosed and curing 95% of treated patients.
Several pilot studies conducted among Georgian HCV genotype 2 patients described unexpectedly high frequency of a natural intergenotypic recombinant strain, designated as RF1_2k/1b. Due to the extremely rare occurrence of RF1_2k/1b strains in HCV clinical trial patients worldwide, no official recommendation exists on diagnostic standards or effective treatment regimen for this strain.
Effectiveness of different DAA regimens among RF1_2k/1b patients was evaluated in a pilot study conducted in 2015 in Georgia. The study reported significantly higher cure rates among RF1_2k/1b patients treated with sofosbuvir/ribavirin in combination with interferon and especially ledipasvir/sofosbuvir/ribavirin compared to standard HCV genotype 2 treatments with 12 or 20 weeks of sofosbuvir/ribavirin. However, small sample size underlined the need for larger studies for reassessing existing methods for the management of HCV genotype 2 infections, especially in areas with high prevalence of the RF1_2k/1b strain.
Even though SVR rates reported among HCV genotype 2 and especially RF1_2k/1b patients are high within Georgia’s national hepatitis C elimination program, total number of patients experiencing virologic treatment failure can be still significant. Increasing emergence of resistance associated substitutions (RASs) among RF1_2k/1b patients could be the serious public health concern and needs immediate attention. Therefore, identifying the impact of RASs on DAA treatment outcomes for RF1_2k/1b patients is extremely important for achieving individual and public health benefit.
The 2 year prospective study is proposed to:
· Study the prevalence of RF1_2k/1b strains by analyzing HCV genomic regions among HCV genotype 2 patients;
· Evaluate DAA treatment outcomes among RF1_2k/1b patients;
· Explore the occurrence of RASs among HCV genotype 2 and RF1_2k/1b patients who failed on DAA treatment and identify impact of baseline NS5A RAS on predicting SVR; and finally
· Evaluate association of RASs with patients’ demographic, epidemiological and clinical characteristics.
We plan to prospectively enroll 400 HCV genotype 2 patients during the 2 year period for studying the prevalence and evaluating DAA treatment outcomes among RF1_2k/1b patients. Additionally 60 patients failing on DAA therapy will be evaluated for the presence of NS5A RASs. Pre- treatment specimens from these 60 patients will be retrospectively analyzed for baseline NS5A RASs.
The study will be implemented by the Infectious Diseases, AIDS and Clinical Immunology Research Center in collaboration with the Hepatology clinic “Hepa. Both institutions are country’s leading providers of HCV care.
Proposed study is the first initiative to identifying impact of RF1_2k/1b viral genomic characteristics and role of RASs on DAA treatment outcomes worldwide.
Georgia is setting an example for possibility of HCV elimination; therefore, understanding HCV molecular characteristics, especially underdiagnosed HCV strains that can influence effectiveness of DAA treatment will definitely provide extremely valuable clinical recommendations for optimizing HCV care worldwide.
Participating Institutions
LEADING
Georgian AIDS and Clinical Immunology Research Center
