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 (112 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 street outreach. 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.
|Dubrow, Robert; Qin, Li; Lin, Haiqun et al. (2017) Association of CD4+ T-cell Count, HIV-1 RNA Viral Load, and Antiretroviral Therapy With Kaposi Sarcoma Risk Among HIV-infected Persons in the United States and Canada. J Acquir Immune Defic Syndr 75:382-390|
|Cepeda, Javier A; Thomas, David L; Astemborski, Jacquie et al. (2017) Increased Mortality Among Persons With Chronic Hepatitis C With Moderate or Severe Liver Disease: A Cohort Study. Clin Infect Dis 65:235-243|
|Anderegg, Nanina; Johnson, Leigh F; Zaniewski, Elizabeth et al. (2017) All-cause mortality in HIV-positive adults starting combination antiretroviral therapy: correcting for loss to follow-up. AIDS 31 Suppl 1:S31-S40|
|Drozd, Daniel R; Kitahata, Mari M; Althoff, Keri N et al. (2017) Increased Risk of Myocardial Infarction in HIV-Infected Individuals in North America Compared With the General Population. J Acquir Immune Defic Syndr 75:568-576|
|Jiamsakul, Awachana; Kariminia, Azar; Althoff, Keri N et al. (2017) HIV Viral Load Suppression in Adults and Children Receiving Antiretroviral Therapy-Results From the IeDEA Collaboration. J Acquir Immune Defic Syndr 76:319-329|
|Veenhuis, Rebecca T; Astemborski, Jacquie; Chattergoon, Michael A et al. (2017) Systemic Elevation of Proinflammatory Interleukin 18 in HIV/HCV Coinfection versus HIV or HCV Monoinfection. Clin Infect Dis 64:589-596|
|Ramsuran, Veron; Hernández-Sanchez, Pedro G; O'hUigin, Colm et al. (2017) Sequence and Phylogenetic Analysis of the Untranslated Promoter Regions for HLA Class I Genes. J Immunol 198:2320-2329|
|Kandathil, Abraham J; Breitwieser, Florian P; Sachithanandham, Jaiprasath et al. (2017) Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs. Ann Intern Med 167:1-7|
|Kirk, Gregory D; Dandorf, Stewart; Li, Huifen et al. (2017) Differential Relationships among Circulating Inflammatory and Immune Activation Biomediators and Impact of Aging and Human Immunodeficiency Virus Infection in a Cohort of Injection Drug Users. Front Immunol 8:1343|
|Vergara, C; Thio, C; Latanich, R et al. (2017) Genetic basis for variation in plasma IL-18 levels in persons with chronic hepatitis C virus and human immunodeficiency virus-1 infections. Genes Immun 18:82-87|
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