CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

1 Universidade de Lisboa, Lisbon, Portugal, 2 Institute of Health Carlos III, Madrid, Spain Background: Any successful strategy to prevent and control HCV infection requires an understanding of the epidemic behaviour of the virus. HCV genotype (GT) 1 is the most prevalent worldwide and GT1a represents almost 40% of the GT1 infections in Spain. We aimed to characterize the origin, epidemic history, transmission dynamics and diversity of HCV-GT1a in Spain. Methods: This study describes a nationwide multicenter (80 Spanish hospitals) cross-sectional study of 588 DAA-treatment naïve patients harboring HCV-GT1a. HCV population sequencing was used to identify relevant resistance-associated substitutions (RASs) to NS5A inhibitors. Phylogenetic analysis was used for subtyping and transmission cluster identification. HCV-GT1a lineages (clade I and clade II) were confirmed by geno2pheno[HCV]. Bayesian methods were used to reconstruct the epidemic history of HCV-GT1a. Results: 51.0% (n=300) were HCV+ and 49.0% (n=288) were HIV+/HCV+ subjects. HCV-GT1a clade II was more prevalent than clade I (82.3%, n=484, vs. 17.7%, n=104; P<0.001). Viruses bearing RASs to NS5A inhibitors were present in 50 samples (8.5%), seven of those having viruses with double RASs. Higher prevalence of RAS was found in clade II (80%).The most common RASs were M28A/T/V (44.0%; n=22/50), Y93C/F/H/N (28.0%; n=14/50) and Q30E/H/R (24.0%; n=12/50). The double mutations 30H+93H, 28V+30R and 30R+93H were also observed. A prevalence of RASs of <10%was observed in eleven regions while a prevalence >10%was observed in five, highlighting Cantabria (15.9%; n=7/44) and Murcia (12.5%; n=1/8). Among patients harboring RASs, those that harbored mutations which confers high resistance were: 38.0% (n=19/50) to daclatasvir, 34.0% (n=17/50) to ledipasvir, 36.0% (n=18/50) to ombitasvir, 6.0% (n=3/50) to elbasvir, 8.0% (n=4/50) to velpatasvir, 4.0% (n=2/50) to pibrentasvir. GT1a clade II epidemic preceded clade I by 45 years [time to the most recent common ancestor (TMRCA), 95% highest posterior density (95%HPD): 1907, 1879–1932 vs 1952, 1939–1965] (Fig1 A-B-C). GT1a clade II epidemic started in Basque Country, was dispersed throughout the entire country and is now declining. The current GT1a clade I epidemic is still mostly concentrated in the North of Spain and Canary Islands (Fig1 D-E). Conclusion: Current HCV GT1a epidemic in Spain is mainly driven by clade I viruses which seem to have different dispersion routes relative to clade II viruses. Close surveillance of patients with NS5A RAS will be important to prevent further therapeutic failures.

1 Johns Hopkins University, Baltimore, MD, USA, 2 University of NewMexico, Albuquerque, NM, USA, 3 YR Gaitonde Center for AIDS Research and Education, Chennai, India, 4 National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA Background: Accurate hepatitis C virus (HCV) incidence estimates are critical for monitoring progress towards hepatitis C elimination goals which include a reduction in HCV incidence of 80% by 2030. Moreover, incidence estimates can help guide local prevention and treatment programming, particularly in the context of the US opioid epidemic. Methods: An inexpensive ($4/sample), Genedia-based HCV IgG antibody avidity assay was evaluated as a platform to estimate cross-sectional, population-level HCV incidence using 1840 anti-HCV+ and RNA+ samples from 875 individuals enrolled in 5 cohort studies in the US and India of whom 220 were HIV+. Using samples collected <2 years following HCV seroconversion, the mean duration of recent infection (MDRI) was calculated by fitting a binomial regression to the probability of appearing recent using a maximum likelihood approach. Among samples collected ≥2 years following HCV seroconversion, a subject-level false recent rate (FRR) was calculated by estimating the probability of appearing recent using an exact binomial test. Factors associated with falsely appearing recent using an avidity index (AI) cutoff <40% among samples collected ≥2 years post seroconversion were determined by Poisson regression with generalized estimating equations and robust variance estimators. We simulated populations reflecting low, moderate, and high burden HCV and HIV epidemics and assessed the approach’s precision to estimate incidence, with a relative standard error (RSE) of 30%. Results: Using an AI cutoff of <40% this approach had an MDRI of 113 days (95%CI:84-146), and FRR of 0.4% (95%CI:0.0-1.2) and 4.6% (95%CI:2.2-8.3) among HIV- and HIV+ individuals, respectively, and did not differ between HCV genotypes 1 and 3. In multivariable analysis, among samples collected from individuals infected for >2 years, an AI<40%was more likely to be observed in HIV+ individuals who had a CD4+ T-cell count <200 cells/µL, adjPRR = 22.0 (95% CI: 6.28, 77.01; p<0.001) compared to HIV- individuals. In hypothetical scenarios of high-risk settings, a sample size of <1000 individuals was needed to accurately estimate HCV incidence (Figure 1). Conclusion: This cross-sectional approach can estimate HCV incidence for the most common genotypes, particularly in populations with low HIV prevalence. This tool can serve as a valuable resource for program and policy planners seeking to monitor and reduce the global burden of HCV.

Poster Abstracts

601 HCV ANTIBODY AVIDITY–BASED METHOD TO ESTIMATE POPULATION- LEVEL INCIDENCE Denali Boon 1 , Veronica Bruce 2 , Eshan U. Patel 1 , Jeffrey Quinn 1 , Aylur K. Srikrishnan 3 , Shanmugam Saravanan 3 , Syed Iqbal 3 , Pachamuthu Balakrishnan 3 , David L. Thomas 1 , Thomas C. Quinn 4 , Andrea Cox 1 , Kimberly Page 2 , Sunil S. Solomon 1 , Shruti H. Mehta 1 , Oliver Laeyendecker 4

CROI 2019 227