HIV prevalence in the US is increasing due to a combination of the stable incidence of HIV (estimate at 53,600/cases year in 2006) and the longer life expectancy due to effective antiretroiral therapies (7). As HIV patients continue to live longer in the setting of effective ART, live disease has become the leading cause of nonAIDS related mortality (1). Because of shared routes of transmission, HCV and HBV are common in HIVinfected patients though other chronic liver diseases such as alcohol and fatty liver disease are also emerging.Epidemiologic data suggests that HIV accelerates liver fibrosis from a variety of liver diseases. Median time to cirrhosis in HIV/HCV coinfected patients is approximately 12 years sooner than HCV monoinfected patients(11,12). In the case of HIV/HBV coinfection, HIV/HBV coinfected patients are more than 8X likely to die from liver disease than those infected with HIV alone and 19X more likely to die from liver disease than HBV monoinfected individuals (14). In HIV monoinfected patients, NASH is emerging as a cause of liver disease. Given the shortage of donor organ, the economic burden of transplant (15), and the aging cohort of HIV + patients with underlying liver disease, there is an urgent need for the development of antifibotic treatments for this population. This application focuses on understanding how HIV interacts with 2 key cells in the liver which play an important in liver inflammation and fibrosis: 1) the activate hepatic stellate cell and 2) the liver macrophages (Kupffer cells). We will also examine if Kupffer cells are a reservoir for HIV in patients who are on antiretroviral therapies. Findings from this application will lead to innovative antifibrotic approaches for HIV + patients that may prevent the need for transplant and will advance our understanding of HIV reservoirs which is critical to finding a cure for HIV.
Endstage liver disease is the most common cause of nonAIDS related mortality in HIV+ patients in the era of effective antiretroviral therapies. Given the shortage of donor organs and the aging HIV+ population, there is an urgent need to develop antifibrotic approaches for this population.
| Mosoian, Arevik; Zhang, Lumin; Hong, Feng et al. (2017) Frontline Science: HIV infection of Kupffer cells results in an amplified proinflammatory response to LPS. J Leukoc Biol 101:1083-1090 |
