This chapter consists of three sections: future directions for biomedical efforts, future directions for social efforts, and a final note of optimism: time is on our side.
The first section begins with an up-to-date discussion of the prospects for an effective vaccine against HIV. It describes the challenges of producing an effective vaccine to a virus that can evade the immune response by a variety of mechanisms and that exists as different strains in different parts of the world. It points out that a few years ago NIH halted vaccine trials in the USA because it was thought unlikely that existing vaccines would be effective. The various experimental models that exist for vaccine research are described, including the use of simian immunodeficiency virus (SIV), which causes AIDS-like symptoms in some strains of monkeys. The studies of live attenuated strains of SIV as a model for a live attenuated HIV vaccine are discussed. It is pointed out correctly that safety of such live HIV vaccines is a major issue and recent data suggests that such live attenuated viruses can cause disease.
New drug development is then considered. Current anti-HIV drugs target only two of the proteins encoded by the HIV genome: reverse transcriptase and protease. In the future, efforts will be made to target other HIV proteins that are essential for the virus life cycle. Three of the most promising new targets are identified as the viral integrase that is required to integrate the viral DNA into the host cell’s DNA, and the regulatory proteins rev and tat. The process of drug discovery is explained, including issues of efficacy versus toxicity and the kinds of laboratory and clinical studies that are required to develop a new drug. The goals of Phase I, Phase II, and Phase III clinical trials are explained.
Another potential class of antiviral drugs that have been studied previously are those that prevent HIV from entering the cell. Attention was initially focused on methods to block the binding of HIV to CD4 on the surface of susceptible cells, but this approach failed to generate new drugs. As stated in this chapter, however, the discovery of co-receptors has rekindled interest in trying to block viral entry and the first generation of drugs targeted at the co-receptor are entering clinical trial. Finally, this section closes with a discussion of molecular biological approaches to anti-HIV drugs that have not yet left the laboratory. One approach is the use of anti-sense constructs that bind to HIV RNA and block replication; the other approach is the use of novel RNA molecules called ribozymes that can cleave the HIV RNA, thus preventing viral expression.
A fundamentally different approach to the treatment of AIDS is then discussed: therapies aimed at restoring the immune system and consequently preventing opportunistic infections. The use of the T cell hormone, IL-2, to boost T cell counts is described in detail. This approach has been used in clinical trials for a number of years, but as is pointed out, there are significant drawbacks to this kind of treatment. One is the side effects of IL-2 treatment and the other is cost.
A section is then devoted to a discussion of new treatments for opportunistic infections and cancers. These would not cure AIDS but potentially could improve quality of life and increase survival.
Finally, the discussion of the future of biomedical AIDS research ends with an interesting section on ideas about how to improve the conduct of AIDS clinical trials.
The section on future directions for social efforts focuses upon the need for effective education and prevention strategies targeted at members of high risk groups. It points out the political opposition to clean needle exchange programs even though there is a consensus in the scientific community that such programs are effective. It also emphasizes the need to develop programs for ethnic groups that have been disproportionately impacted by the AIDS, and the need to provide education to reduce the ignorance and fear of some members of the public that foster prejudice, discrimination, and hatred against people with HIV/AIDS. The need for continued epidemiological studies and survey research is also stressed. Importantly, the section ends with a call for better evaluation of HIV and AIDS programs using objective criteria to measure outcomes.
The final section of the chapter serves as an epilogue full of optimism. It argues that the years it takes for HIV-infected individuals to develop AIDS provides a window of opportunity to develop new therapies. It also correctly points to how rapidly AIDS was recognized as a new disease and the causal agent identified and the rapid progress that has been made in developing effective therapies. The fact that these therapies have dramatically reduced AIDS-related deaths in the last few years is balanced by the recognition that the rate of new HIV infections has not been reduced. NOTE Following this chapter is a comprehensive glossary that is particularly useful for students with a limited biology background. |
