In this competing renewal, we propose to continue a 25-year investigation of the epidemiology of HIV risk among HIV-uninfected injection drug users (IDUs) enrolled in the AIDS Linked to the IntraVenous Experience (ALIVE-II) Study in Baltimore, MD. This study has provided critical insight into the dynamics of HIV infection and risk behavior while serving as a comparison group to a parallel cohort of HIV positive IDUs (DA04334, ALIVE-I). Our investigative team has been highly productive during the past funding cycle (105 publications &77 major presentations) and, over the next five years, we will continue cutting-edge and innovative broad- based investigations, while serving as a resource for clinical and pathogenesis studies related to HIV and HCV infection. In this proposal, we present a focused effort related to hepatitis C virus (HCV), which represents the major challenge that IDUs will face over the next decade. HCV prevalence ranges from 50-90% in IDU populations and morbidity and mortality secondary to HCV infection is expected to dramatically increase over the next decade. Building on lessons learned from HIV, we focus on collecting information to evaluate the population-level effectiveness of current HCV 'Test-and-Treat'initiatives and provide insight to the development of new interventions to target HCV testing, linkage to care, treatment and Treatment as Prevention (HCV-TasP).
Our Specific Aims are to: 1) Characterize the continuum of care for HCV among IDUs and its evolution over time with increasingly efficacious antiviral therapy;2) Assess population-level effectiveness of hepatitis C treatment among IDUs in Baltimore;3) Develop a mathematical model of HCV treatment dynamics to assess the potential impact and cost-effectiveness of different intervention strategies;and 4) continue to serve as an HIV negative comparison group for longitudinal investigation of non-AIDS outcomes and a platform for independently funded related studies. To achieve these aims, we will continue follow-up of a cohort of HIV negative IDUs (~1000) with semiannual visits and will open recruitment twice over the proposed funding period. New recruitment will occur in 2013-2014 and 2016-2017;500 participants at each time point will be accrued via respondent-driven sampling. The ALIVE-II cohort is unique in that it comprises a community-based IDU population of both genders with significant representation of African-Americans and those with limited access to appropriate medical care;these populations have been underrepresented in research on persons at risk for HIV infection. We collaborate with ALIVE-I, a parallel cohort of HIV-infected IDUs that capitalizes on the same protocol, facilities and staff with no fiscal overlap. Given the scientific rigor of the proposed methods, existing infrastructure, experienced investigators and multiple NIH-funded ancillary studies, we anticipate continued success and substantial scientific contribution.
While advances in treatment and prevention for HIV have led to reduced incidence of HIV among injection drug using (IDUs) populations, >80% are infected with hepatitis C virus (HCV) making it one of the greatest challenges IDUs will face over the next decade. The findings from this study will inform interventions to improve uptake of testing and treatment for hepatitis C at this critical time when major advances in hepatitis C treatment are expected.
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|Wojcik, G L; Thio, C L; Kao, W H L et al. (2014) Admixture analysis of spontaneous hepatitis C virus clearance in individuals of African descent. Genes Immun 15:241-6|
|Mehta, Shruti H; Srikrishnan, Aylur K; Noble, Eva et al. (2014) Emergence of cocaine and methamphetamine injection among HIV-positive injection drug users in northern and western India. Drug Alcohol Depend 135:160-5|
|Wojcik, Genevieve; Latanich, Rachel; Mosbruger, Tim et al. (2014) Variants in HAVCR1 gene region contribute to hepatitis C persistence in African Americans. J Infect Dis 209:355-9|
|Aka, Peter V; Kuniholm, Mark H; Pfeiffer, Ruth M et al. (2014) Association of the IFNL4-Î”G Allele With Impaired Spontaneous Clearance of Hepatitis C Virus. J Infect Dis 209:350-4|
|Duggal, Priya; Thio, Chloe L; Wojcik, Genevieve L et al. (2013) Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts. Ann Intern Med 158:235-45|
|Chatziandreou, Nikolaos; Arauz, Ana Belen; Freitas, Ines et al. (2012) Sensitivity changes over the course of infection increases the likelihood of resistance against fusion but not CCR5 receptor blockers. AIDS Res Hum Retroviruses 28:1584-93|
|Drummond, M Bradley; Kirk, Gregory D; Astemborski, Jacquie et al. (2012) Association between obstructive lung disease and markers of HIV infection in a high-risk cohort. Thorax 67:309-14|
|Khosla, Nidhi; Juon, Hee Soon; Kirk, Gregory D et al. (2011) Correlates of non-medical prescription drug use among a cohort of injection drug users in Baltimore City. Addict Behav 36:1282-7|
|Mehta, Shruti H; Buckle, Geoffrey C (2011) Assessment of liver disease (noninvasive methods). Curr Opin HIV AIDS 6:465-71|
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