CROI 2019 Abstract eBook

Abstract eBook

Poster Abstracts

Results: Roughly 90% sequencing success rates, defined as achieving >100- fold NGS read coverage across NS3, NS5a and NS5b, was observed for most genotypes in samples with HCV RNA >5 log10 IU/mL (Table 1). The genotype- independent HCV method showed >99.8% nucleotide concordance with the GT1-optimized method in NS3, NS5a, and NS5b using a 20%mixture-calling threshold. The assay demonstrated near-perfect precision and reproducibility at detecting variants above 2% prevalence and showed no systematic bias in amplifying specific RAS. An absolute lower limit of 0.2% for reproducible minor species detection was estimated but warrants a more conservative threshold given MiSeq error rates (0.5%) and limitations of PCR. Conclusion: This study highlights the performance of a freely available, near whole-genome NGS assay and bioinformatic pipeline for genotype- independent HCV genotyping and RAS detection. The method demonstrated similar performance to a validated GT1 assay and can now be extended to other HCV genotypes. This method has been implemented clinically and has been used to deliver ~3000 resistance test reports to physicians across Canada.

Conclusion: Nearly 1 in 5 MSM screened for HPTN 078 have been infected with HCV in a high HIV burden sample. The prevalence is high regardless of HIV infection status and is high even in those who did not undergo substance use counseling. These data raise concern that in HIV burden networks high HCV infection prevalence may occur in HIV-uninfected MSM. HCV transmission risk could increase as PREP implementation expands and condom use declines among HCV positive MSM. Further work is needed to understand the high HCV antibody prevalence in this cohort. 597 EPIDEMIC HISTORY OF HEPATITIS C VIRUS AMONG MSM IN AMSTERDAM, THE NETHERLANDS Jelle Koopsen 1 , Thijs J. Van de Laar 2 , Colin Russell 1 , Maria Prins 3 , Elske Hoornenborg 3 , Alvin Han 4 , Edyth Parker 5 , Marc van der Valk 1 , Janke Schinkel 1 1 Academic Medical Center, Amsterdam, Netherlands, 2 Sanquin Research, Amsterdam, Netherlands, 3 Public Health Service Amsterdam, Amsterdam, Netherlands, 4 Agency for Science, Technology and Research, Queenstown, Singapore, 5 Cambridge University, Cambridge, UK Background: To strengthen HCV micro-elimination efforts in the MSM community, a better understanding of transmission networks is vital. Insight in the proportion of new HCV infections that results from ongoing transmission of local variants versus new infections via external introductions may further guide specific local elimination efforts. We describe the epidemic history of HCV infections among MSM in Amsterdam from 1994 to 2018. Methods: Sanger sequencing of part of the E1E2 genomic region (525 base pairs) was applied to 147 samples positive for HCV gt1a – the most prevalent genotype in Amsterdam (62%) – fromMSM diagnosed between 1994 and 2018. The majority of MSM was HIV positive (87%) and diagnosed during the acute phase of the infection (91%). Time-resolved phylogenetic analyses were performed using BEAST software to estimate the temporal origin and progression of the HCV epidemic in Amsterdam. PhyCLIP software was used for statistically supported cluster designation. Results: 114 sequences (78%) grouped into seven clusters with introduction dates ranging from 1996 to 2004. Cluster sizes ranged from three to thirty-seven sequences. A modest decrease in proportion of clustered sequences over time was observed: 80% (36/45) of samples from 2008-2013 and 70% (40/57) of samples from 2013-2018 were part of a cluster. We observed that the ratio non- clustered to clustered sequences remained fairly stable until 2015 (mean ratio 0.14, SD = 0.10), after which the ratio increased to 1.2 in 2018 (n=11) in favor of the non-clustered sequences. Conclusion: The identification of both non-clustered and clustered infections, in particular in the past five years, indicates that both external introductions and ongoing transmission within existing clusters fuel the HCV epidemic among MSM in Amsterdam. The seeming increase in external introductions when compared to local transmission coincides with the beginning of the DAA era in the Netherlands. Prospective, phylogenetic analysis of recent HCV infections combined with data collection on network characteristics of the individuals infected with HCV (e.g. meeting location of sex partners) has the potential to guide targeted prevention measures and stresses the need for real-time HCV sequence monitoring in the Netherlands.

Poster Abstracts

596 HPTN 078: HIGH PREVALENCE OF HCV ANTIBODIES AMONG MEN WHO HAVE SEX WITH MEN Risha Irvin 1 , Theresa Gamble 2 , Jowanna Malone 3 , Zhe Wang 4 , Ethan A. Wilson 4 , James P. Hughes 4 , Jason Farley 5 , Kenneth H. Mayer 6 , Carlos del Rio 7 , D. Scott Batey 8 , Susan H. Eshleman 1 , Robert H. Remien 9 , Chris Beyrer 3 , Chloe Thio 1 , for the HPTN 078 Research Group 1 Johns Hopkins University School of Medicine, Baltimore, MD, USA, 2 FHI 360, Durham, NC, USA, 3 Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA, 4 Statistical Center for HIV/AIDS Research and Prevention, Seattle, WA, USA, 5 Johns Hopkins University, Baltimore, MD, USA, 6 The Fenway Institute, Boston, MA, USA, 7 Emory University, Atlanta, GA, USA, 8 University of Alabama at Birmingham, Birmingham, AL, USA, 9 Columbia University, New York, NY, USA Background: Sexual transmission of hepatitis C virus (HCV) is uncommon, yet has been documented among MSM, primarily among those who are HIV- infected. Recent phylogenetic analyses reveal that some HIV-uninfected MSM are infected with HCV strains circulating in HIV-infected MSM transmission networks. Data on the prevalence of HCV infection in HIV-uninfected MSM are limited. Methods: In HPTN 078, which assessed the efficacy of an integrated strategy to achieve HIV viral suppression, 1305 MSM were screened using respondent driven sampling or direct recruitment across four geographically diverse US cities. HIV- infected MSM with viral loads >1,000 copies/mL were eligible for enrollment. At screening, demographic, behavioral, and psychosocial questionnaires were completed, along with HIV and HCV antibody testing. Multivariable logistic regression was used to evaluate associations with HCV antibody positivity. Results: Of the 1305 men screened, median age was 41, 69%were Black, 85% had a high school diploma or more, 84% had either public or private insurance, 35%were employed, 69%were HIV-infected, and 20% had undergone substance use counseling/treatment. The median lifetime number of male sexual partners was 17 (IQR: 6, 50) and female partners was 5 (2, 13). HCV antibody test results were available for 1287 (99%) of the men of whom 246 (19%) were positive. HCV antibody positivity was high in both HIV-infected (20%) and HIV-uninfected (16%) MSM (P=0.12) and was higher in those receiving substance use counseling/treatment (36%) than those that had not (15% )(P=<0.01). After adjusting for other factors, older age [odds ratio (OR) 1.06 per year, 95% CI 1.05-1.08], less than a high school degree [OR 1.71, 95% CI 1.15-2.55], drug/alcohol counseling or treatment [OR 2.57, 95% CI 1.83-3.61] and unstable housing [OR 2.16, 95% CI 1.29-3.61] were associated with increased risk for HCV antibody positivity.

CROI 2019 225