Understanding of the spectrum of the HIV and HCV epidemics in injection drug users (IDU) has been advanced by a number of outstanding prospective studies conducted in various part of the world, including, North America, Europe, and Australia. Each of these studies has furthered our understanding of disease prevalence and incidence, risk behaviors, and natural history, including clinical, immunological and virological factors. This application seeks funding for the first global collaboration of prospective studies of HIV and HCV in IDU. The """"""""International Collaboration of Incident HIV and HCV in Injecting Cohorts"""""""" (InC3), is merged international multi-cohort project of pooled biological and behavioral data from nine prospective cohorts of IDU. The InC3 collaboration will facilitate new in-depth studies of HIV and HCV infection not possible from each individual study. This collaboration will allow us to study 4,091 IDU who have been followed for a collective 9,016 person-years of observation, 859 incident HCV infections with longitudinal follow up, and 575 HIV infections. This proposal includes six research questions that represent some, but not all, of the potential breadth and depth of the proposed InC3 research collaboration, including: assessment of temporal trends in HIV and HCV incidence, examination of HCV incidence by HIV status and sexual behavior, estimates of rates and determinants of HCV viral clearance and reinfection, examination of the effects of HCV infection disclosure are on risk behaviors, and an evaluation of outcomes related to clinical treatment of acute HCV in IDU. Many of these questions remain unanswered due to the relatively small number of small numbers of behavioral, viral, or clinical events in each study. However, since many have been meticulously characterized in each of these rich longitudinal cohorts, merging data will offer the statistical power needed to make firm conclusions. The significant and innovative scientific agenda and the InC3 leadership will be supported by an administrative core and Data Coordinating Center (DCC). InC3 will promote and support the development of new study questions and research opportunities through supporting research exchange and training for participating junior scientists. Lastly, some gaps in biological data will be addressed with support for laboratory measures from stored specimens. This proposed InC3 study, will accomplish the following: (1) creation of a rich new data source that will fill scientific knowledge gaps that heretofore have not been possible in single studies alone;(2) enable new research relevant to understanding, preventing, and treating HIV and HCV in IDU;(3) the creation of a multilateral collaborative of researchers and scientists committed to long term cooperation and partnership in areas including: epidemiology, behavioral studies, clinical research, and laboratory science. Many of the investigators of this proposed multicenter project are experienced and successful in pooling and analyzing large epidemiological data in both a national, and international, context. Despite the obvious benefits to public health, such an organized effort has never been attempted with cohorts that have studied both HIV and HCV. InC3 is significant, innovative, will advance research relevant to the global burden, consequences, prevention, and treatment of HIV and HCV infections among IDU.

Public Health Relevance

This international collaboration: the InC3, will create a merged international multi-cohort project of data pooled from nine prospective studies of IDU conducted in four countries over 22 years. The collaboration will result in the largest dataset available for analyses and research on HIV and HCV infections in IDU, including acute HCV infection and HIV/HCV co-infections. The combined expertise and research data will advance research relevant to the global burden, consequences, prevention, and treatment of HIV and HCV infections among IDU.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA031056-03
Application #
8460542
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Hartsock, Peter
Project Start
2011-05-15
Project End
2016-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
3
Fiscal Year
2013
Total Cost
$413,985
Indirect Cost
$56,383
Name
University of California San Francisco
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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Rodrigo, Chaturaka; Walker, Melanie R; Leung, Preston et al. (2017) Limited naturally occurring escape in broadly neutralizing antibody epitopes in hepatitis C glycoprotein E2 and constrained sequence usage in acute infection. Infect Genet Evol 49:88-96
Rodrigo, C; Eltahla, A A; Bull, R A et al. (2017) Phylogenetic analysis of full-length, early infection, hepatitis C virus genomes among people with intravenous drug use: the InC3 Study. J Viral Hepat 24:43-52
Rodrigo, Chaturaka; Eltahla, Auda A; Bull, Rowena A et al. (2016) Historical Trends in the Hepatitis C Virus Epidemics in North America and Australia. J Infect Dis 214:1383-1389
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Page, Kimberly; Mirzazadeh, Ali; Rice, Thomas M et al. (2016) Interferon Lambda 4 Genotype Is Associated With Jaundice and Elevated Aminotransferase Levels During Acute Hepatitis C Virus Infection: Findings From the InC3 Collaborative. Open Forum Infect Dis 3:ofw024
Doyle, J S; Deterding, K; Grebely, J et al. (2015) Response to treatment following recently acquired hepatitis C virus infection in a multicentre collaborative cohort. J Viral Hepat 22:1020-32
Iversen, Jenny; Page, Kimberly; Madden, Annie et al. (2015) HIV, HCV, and Health-Related Harms Among Women Who Inject Drugs: Implications for Prevention and Treatment. J Acquir Immune Defic Syndr 69 Suppl 2:S176-81
Page, Kimberly; Tsui, Judith; Maher, Lisa et al. (2015) Biomedical HIV Prevention Including Pre-exposure Prophylaxis and Opiate Agonist Therapy for Women Who Inject Drugs: State of Research and Future Directions. J Acquir Immune Defic Syndr 69 Suppl 2:S169-75
Sacks-Davis, Rachel; Grebely, Jason; Dore, Gregory J et al. (2015) Hepatitis C Virus Reinfection and Spontaneous Clearance of Reinfection--the InC3 Study. J Infect Dis 212:1407-19

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