Cellular Restriction Factors: Exploiting the Body’s Antiviral Proteins to Combat HIV-1/AIDS

Introduction 1.1 Overview of HIV-1/AIDS therapiesIn 1983, when researchers first isolated HIV-1 from an AIDS patient, few imagined that it foretold a worldwide pandemic (Broder & Gallo, 1984, Barre-Sinoussi et al., 1983).More than 25 years later, 65 million people have been infected with HIV-1; nearly half of these people have died of AIDS, and despite many scientific advances we are still without an efficacious vaccine (Merson, 2006).The majority of HIV-1 infections and deaths have occurred in developing countries, with sub-Saharan Africa accounting for over 38 million HIV-1 infections alone.Sadly, the number of new infections currently exceeds our ability to treat everyone infected with the virus, and in the hardest-hit countries the social and economic backlash has been profound.After HIV-1 was isolated, a blood test to screen patients and the blood supply quickly followed, as did research on its structure and pathogenesis.Many assumed that a vaccine would be available in a few years, and excitement increased further with the licensing of the first effective drug against HIV-1, zidovudine (AZT) (Fischl et al., 1987).However, researchers soon discovered that the virus was highly resilient, and HIV-1 quickly developed resistance to AZT (Poli et al., 1989, Richman et al., 1994).Over the next few years, a number of new antiretroviral drugs were developed that attacked the virus in different ways, and it was at this time that a new approach to therapy ensued.Highly active antiretroviral therapy (HAART) combined three or more different drugs to reduce HIV-1 replication, and significantly improved the prognosis of HIV-1-infected individuals (Richman et al., 2009).However, HAART was not a cure, and many patients were resistant to at least one of the antiretroviral drugs.In addition, the drugs were highly toxic, making adherence to treatment difficult.During this time, the vaccine field was also hard at work, trying to develop a safe and effective HIV-1 vaccine.Most initial vaccine approaches focused on the HIV-1 envelope protein (gp120), and aimed to induce an antibody response to gp120.AIDSVAX was the first vaccine candidate of this type, and was developed by a U.S. pharmaceutical company called VaxGen (Flynn et al., 2005, Pitisuttithum et al., 2006).An alternative approach, developed by Merck, aimed to induce a T-cell response to HIV-1 using a recombinant adenovirus vector expressing HIV-1 Gag, Pol and Nef proteins (Shiver et al., 2002).Unfortunately, results from www.intechopen.

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