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Molecular Understanding of HIV-1 Latency

DOI: 10.1155/2012/574967

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Abstract:

The introduction of highly active antiretroviral therapy (HAART) has been an important breakthrough in the treatment of HIV-1 infection and has also a powerful tool to upset the equilibrium of viral production and HIV-1 pathogenesis. Despite the advent of potent combinations of this therapy, the long-lived HIV-1 reservoirs like cells from monocyte-macrophage lineage and resting memory CD4+ T cells which are established early during primary infection constitute a major obstacle to virus eradication. Further HAART interruption leads to immediate rebound viremia from latent reservoirs. This paper focuses on the essentials of the molecular mechanisms for the establishment of HIV-1 latency with special concern to present and future possible treatment strategies to completely purge and target viral persistence in the reservoirs. 1. Introduction Infection with HIV-1, which was first isolated in 1983, causes AIDS, a syndrome that was first reported in 1981 [1]. The HIV-1 pandemic represents one of the great plagues in the history of mankind and a major challenge for medicine, public health, and medical research [2]. The majority of people living with HIV-1 belong to low- and middle-income countries. For example, sub-Saharan Africa accounts for two third of all infected people with HIV-1, where in few countries more than one in five adults are infected with HIV. South and south East Asia have second highest number of people living with HIV-1. Furthermore the epidemic is spreading most rapidly in Eastern Europe and central Asia, where the number of people living with HIV increased by 54.2% between 2001 and 2009. UNAIDS estimated that 33.3 million people were infected with HIV at the end 2009 compared to 26.2 million in 1999, a 27% increase in HIV infection. Each year 2.6 million people are infected with HIV-1 and 1.8 million die of AIDS (UNAIDS 2010). Much has been learned about the science of AIDS and continuous research has allowed the development of 25 different active compounds belonging to six different drug families shifting the HIV-1 infection from a fatal illness into a chronic disease [3, 4]. HIV-1 life cycle can be categorized into two phases. The early stage occurs between entry into host cells and integration into its genome (Figure 1). The late phase occurs from the state of integrated provirus to full viral replication [5]. Similarly two types of viral latency can be differentiated: preintegration latency results in generation of different forms of viral DNA before integration, whereas postintegration latency refers to the lack of viral replication

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