Epigenetic regulation of HIV, AIDS, and AIDS-related malignancies.

Abstract

Although epigenetics is not a new field, its implications for acquired immunodeficiency syndrome (AIDS) research have not been explored fully. To develop therapeutic and preventive approaches against the human immunodeficiency virus (HIV) and AIDS, it is essential to understand the mechanisms of interaction between the virus and the host, involvement of genetic and epigenetic mechanisms, characterization of viral reservoirs, and factors influencing the latency of the virus. Both methylation of viral genes and histone modifications contribute to initiating and maintaining latency and, depending on the context, triggering viral gene repression or expression. This chapter discusses progress made at the National Institutes of Health (NIH), recommendations from the International AIDS Society Scientific Working Group on HIV Cure, and underlying epigenetic regulation. A number of epigenetic inhibitors have shown potential in treating AIDS-related malignancies. Epigenetic drugs approved by the US Food and Drug Administration and their implications for the eradication of HIV/AIDS and AIDS-related malignancies also are discussed.Past and current progress in developing treatments and understanding the molecular mechanisms of AIDS and HIV infection has greatly improved patient survival. However, increased survival has been coupled with the development of cancer at higher rates than those observed among the HIV/AIDS-negative population. During the early days of the AIDS epidemic, the most frequent AIDS-defining malignancies were Kaposi's sarcoma and non-Hodgkin lymphoma (NHL). Now, with increased survival as the result of widespread use in the developed world of highly active antiretroviral therapy (HAART), non-AIDS defining cancers (i.e., anal, skin, and lung cancers, and Hodgkin disease) are on the increase in HIV-infected populations. The current status of AIDS-related malignancies also is discussed.