The research program funded by R01 013806 is focused on liver fibrosis progression in HIV/HCV coinfected persons. Liver disease is one of the leading causes of death in HIV infected persons, and its public health importance is expected to increase. As treatments for both HIV and HCV improve, the important clinical questions now are treatment-related. Does antiretroviral therapy (ART) affect progression of liver disease and therefore need to be given to HIV/HCV coinfected persons even at high CD4+ lymphocyte counts? Is suppression of HCV replication by treatment sufficient to stop fibrosis progression? Does the chronic immune activation caused by HIV contribute to IFN resistance and can ART diminish that effect? In the next funding cycle, we plan to answer these and other questions related to the """"""""treated"""""""" history of HIV/HCV coinfected persons by a series of integrated clinical and laboratory studies that build on the models of natural history and pathogenesis that we and others have developed over the past decade.
The specific aims are as follows:
Aim 1 is to test the hypothesis that effective antiretroviral therapy reduces progression of liver fibrosis in HIV/HCV coinfected persons.
Aim 2 is to test the hypothesis that suppression of HCV replication by treatment reduces liver fibrosis progression in HIV/HCV coinfected persons.
Aim 3 is to test the hypothesis that interferon alfa (IFN) sensitivity is improved by antiretroviral therapy.
The aims of prior funding cycles have been accomplished and reported among 25 peer reviewed articles supported by R01 013806. The current aims are revised to answer significant scientific questions during the next period using innovative research tools. There is a high likelihood that these studies will inform U.S. Public Health Service guidelines on when to start antiretroviral therapy and provide a scientific basis for existing guidelines governing treatment of HCV infection in persons with HIV.

Public Health Relevance

The proposed research is designed to guide significant clinical decisions, such as when to start antiretroviral therapy in the 25% of HIV infected persons who have chronic hepatitis C and whether treatment for HCV infection can be justified to prevent progression of liver disease. The studies might also explain why treatments for chronic hepatitis C are not as effective in persons dually infected with HIV.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DA013806-13
Application #
8262391
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Khalsa, Jagjitsingh H
Project Start
2000-09-20
Project End
2015-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
13
Fiscal Year
2012
Total Cost
$646,848
Indirect Cost
$236,301
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Wansom, Tanyaporn; Falade-Nwulia, Oluwaseun; Sutcliffe, Catherine G et al. (2017) Barriers to Hepatitis C Virus (HCV) Treatment Initiation in Patients With Human Immunodeficiency Virus/HCV Coinfection: Lessons From the Interferon Era. Open Forum Infect Dis 4:ofx024
Naggie, Susanna; Holland, David P; Sulkowski, Mark S et al. (2017) Hepatitis C Virus Postexposure Prophylaxis in the Healthcare Worker: Why Direct-Acting Antivirals Don't Change a Thing. Clin Infect Dis 64:92-99
Falade-Nwulia, Oluwaseun; Sutcliffe, Catherine; Moon, Juhi et al. (2017) High hepatitis C cure rates among black and nonblack human immunodeficiency virus-infected adults in an urban center. Hepatology 66:1402-1412
Seremba, Emmanuel; Ssempijja, Victor; Kalibbala, Sarah et al. (2017) Hepatitis B incidence and prevention with antiretroviral therapy among HIV-positive individuals in Uganda. AIDS 31:781-786
El-Diwany, Ramy; Breitwieser, Florian P; Soliman, Mary et al. (2017) Intracellular HIV-1 RNA and CD4+ T-cell activation in patients starting antiretrovirals. AIDS 31:1405-1414
Lazo, Mariana; Nwankwo, Chizoba; Daya, Natalie R et al. (2017) Confluence of Epidemics of Hepatitis C, Diabetes, Obesity, and Chronic Kidney Disease in the United States Population. Clin Gastroenterol Hepatol 15:1957-1964.e7
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
Falade-Nwulia, O; Mehta, S H; Lasola, J et al. (2016) Public health clinic-based hepatitis C testing and linkage to care in Baltimore. J Viral Hepat 23:366-74
Cepeda, Javier A; Solomon, Sunil S; Srikrishnan, Aylur K et al. (2016) Serum Fibrosis Markers for the Diagnosis of Liver Disease Among People With Chronic Hepatitis C in Chennai, India. Open Forum Infect Dis 3:ofw156
Wasilewski, Lisa N; El-Diwany, Ramy; Munshaw, Supriya et al. (2016) A Hepatitis C Virus Envelope Polymorphism Confers Resistance to Neutralization by Polyclonal Sera and Broadly Neutralizing Monoclonal Antibodies. J Virol 90:3773-82

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