ACE Inhibitors to Decrease Lymphoid Fibrosis and the Size of the Latent Reservoirin Antiretroviral-Treated, HIV-infected Patients: A Pilot Study
Award amount: 40,000.00
The use of highly active antiretroviral therapy (HAART) has resulted in the marked decline in the morbidity and mortality associated with HIV infection. However, despite this success, current antiretroviral therapy has limitations and does not achieve a cure. Eradication of HIV will likely require a combination of strategies, including therapies that bolster the host?s immune system and that re-activate the HIV latent reservoirs. The majority of the latent reservoir in treated patients resides in the secondary lymphoid tissues including lymph nodes. Early on in HIV infection, the lymphoid architecture is disrupted by collagen deposition and fibrosis prevents effective interaction between antigen-presenting cells (APCs) and cytotoxic T lymphocytes. Angiotensin converting enzyme (ACE) inhibitors have anti-fibrotic properties through inhibition of TGF-?1. Therefore, our hypothesis is that treatment with ACE-inhibitors will lead to decreased fibrosis in lymph nodes and result in improved HIV-specific responses and decreased levels of proviral DNA and cell-associated RNA. To test this hypothesis, we will be conducting a proof-of-concept, pathogenesis-oriented, randomized placebo-controlled study in which antiretroviral-treated, HIV-infected individuals will receive an ACE inhibitor vs. placebo for 24 weeks. Data will be analyzed to determine whether there are significant differences in lymphoid fibrosis, HIV-specific responses and the size of the latent reservoir, between the two groups.