Vaginal microbicides for the prevention of HIV transmission

The human immunodeficiency virus (HIV) kills more people worldwide than any other infectious disease. Approximately 42 million people, mostly in Africa and Asia, are currently infected with HIV (Figure 3.1), and 5 million new infections occur every year (AIDS Epidemic Update, 2002). It is estimated that 22 milIion people have died since the first clinical evidence of AIDS (acquired immunodeficiency syndrome) emerged in 1981 ('Mobilization for Microbicides' ~ The Rockfeller Foundation). HIV is generally transmitted in one of three ways: through unprotected sexual intercourse, blood-to-blood contact, and mother-to-child transmission. Once the virus has entered the body, it invades the cells of the immune system and initiates the production of new virus particles with concomitant destruction of the immune cells. As the number of immune cells in the body slowly declines, weight loss, debilitation, and eventually death occur due to opportunistic infections or cancers. Although AIDS is presently incurable, highly active antiretroviral therapy (HAART), where a cocktail of potent antiretroviral drugs are administered daily to HIV-positive patients to control the viral load, has resulted in dramatic reductions in HIV-related morbidity and mortality in the developed world

Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection

Virus-specific CD8+ T cells are known to play an important role in the control of HIV infection. In this study we investigated whether there may be qualitative differences in the CD8+ T cell response in HIV-1- and HIV-2-infected individuals that contribute to the relatively efficient control of the latter infection. A molecular comparison of global TCR heterogeneity showed a more oligoclonal pattern of CD8 cells in HIV-1- than HIV-2-infected patients. This was reflected in restricted and conserved TCR usage by CD8+ T cells recognizing individual HLA-A2- and HLA-B57-restricted viral epitopes in HIV-1, with limited plasticity in their response to amino acid substitutions within these epitopes. The more diverse TCR usage observed for HIV-2-specific CD8 T cells was associated with an enhanced potential for CD8+ expansion and IFN- production on cross-recognition of variant epitopes. Our data suggest a mechanism that could account for any possible cross-protection that may be mediated by HIV-2-specific CD8+ T cells against HIV-1 infection. Furthermore, they have implications for HIV vaccine development, demonstrating an association between a polyclonal, virus-specific CD8+ T cell response and an enhanced capacity to tolerate substitutions within T cell epitopes.