Drugs in Clinical Development for HIV
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Pharm Med 2011; 25 (2): 95-105 1178-2595/11/0002-0095/$49.95/0
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Drugs in Clinical Development for HIV Summary and Table
HIV is a global pandemic that has killed in excess of 25 million people since the virus was first discovered in 1981. In that time, approximately 40 million people have been infected or 0.6% of the world’s population. In 2008 alone, there were 2.7 million new cases and 2 million HIV/AIDS-related deaths worldwide. Although the worldwide estimated numbers of new infections have been falling year on year since 1996, prevalence continues to rise in many regions, and the number of people living with the disease has increased approximately 3-fold. HIV/AIDS is currently the leading cause of death in Africa. By 2025, mortality is expected to rise to 90 million in Africa, 31 million in India and 18 million in China, according to United Nations’ figures. In the last 30 years, great progress has been made in extending the life expectancy of infected individuals by delaying the progression of HIV to AIDS. Combination antiretroviral therapy has improved the prognosis from fatal to manageable chronic illness by controlling viral replication and reducing viral load. Nonetheless, existing drug cocktails have issues surrounding adherence, resistance and cumulative toxicity and, to date, the goal of finding a safe and effective way of eradicating the virus from the body or stopping the initial infection has failed. Advances in our understanding of the biology and immunopathology of HIV, its mode of transmission and how the human body responds to infection, while incomplete, are improving, and will hopefully pave the way towards designing new drugs and vaccines. Current thinking suggests that a successful HIV vaccine will need multiple effects, including the ability to affect an immune response by inducing both high titre neutralizing antibodies, to prevent infection at mucosal sur-
faces, and cytotoxic T lymphocytes that recognize multiple strains of the virus, to control the spread and replication of any virus that escapes neutralization. Furthermore, in those who do become infected, a vaccine might be expected to reduce steadystate viral load and CD4+ cell count decline before ramped-up viral production takes effect. Although a number of monoclonal antibodies have been identified that target the viral envelope, few have been shown to neutralise a broad range of heterologous viruses. Studies seeking to identify novel, naturally-occurring, cross-reactive neutralising antibodies are ongoing, utilizing high-throughput assays, single-cell sorting techniques and probes with antigenic specificity for the CD4 binding site of viral envelope glycoprotein 120. There have also been clinical successes of late, such as the promising phase III RV144 trial conducted in Thailand, where vaccination with ALVAC and AIDSVAX was shown to reduce the risk of HIV-1 infection by 31% in the modified intent-totreat analysis. Although, interestingly, vaccination was not shown to affect
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