Book Review

HIV and the Pathogenesis of AIDS

N Engl J Med 1995; 333:1016October 12, 1995

Article

HIV and the Pathogenesis of AIDS
By Jay A. Levy. 359 pp., illustrated. Washington, D.C., ASM Press, 1994. $49. ISBN: 1-55581-076-4

This timely and comprehensive work critically analyzes the history of AIDS, virologic and molecular aspects of the human immunodeficiency virus (HIV), and mechanisms of HIV infection. This work was originally written for Microbiological Reviews but has been expanded and updated.

The book begins with an overview of the history of one of the most important public health problems of our century. Levy believes that the elucidation of the mechanisms of viral pathogenesis will inevitably lead to effective control, and prevention, of HIV infection and long-term amelioration of its clinical sequelae. His book presents a stepwise, clearly written, balanced, and extraordinarily well referenced review of the pathobiology of HIV. This book will be of great assistance to any clinical or basic-science investigator who seeks a broad understanding of research problems pertinent to HIV infection. No other single work reviews mechanisms of viral disease in such a well-organized fashion. Of the 90,000 references on HIV and AIDS published since 1981, Levy has selected nearly 2000, thus providing an excellent bibliography. However, since the references are listed alphabetically by author, the reader must work to find the articles cited.

Appendixes deal with clinical categories of HIV infection, the classification and surveillance of HIV and AIDS, and lymphocyte monitoring. Some chapters are better written and more comprehensive than others, and, in some instances Levy's interpretation of disease mechanisms is biased. Alternative ideas are sometimes glossed over or not accepted. Nevertheless, the book follows a logical sequence, and a wide audience should easily understand it. Individual chapters usually close with a useful paragraph of conclusions and questions and directions for future research. This feature should make the book particularly helpful to new investigators.

Chapters on transmission, early infection, and immune responses offer readers an up-to-date overview of HIV type 1 and, where appropriate, HIV type 2. Levy frequently relates pathogenesis to the clinical state. The chapter on cancer in patients with AIDS focuses on Kaposi's sarcoma, lymphoma, and anal carcinoma. Three pages (including illustrations) deal with anal carcinoma, but there is only one paragraph on cervical carcinoma. The section on HIV infection of the central nervous system is more a laundry list of cells that could be infected by HIV and of mechanisms that may have a role in disease than an integrated discussion of viral and host factors. Why do only some patients die of brain disease? Why do some patients have encephalitis but no encephalopathy, or vice versa? How do neurovirulence, neurotropism, and neuroinvasiveness apply to HIV infections of the brain?

Levy presents an interesting two-phase theory of long-term survival after HIV infection. During phase 1, CD4+ helper T cells are gradually lost, and the remaining few are insufficient to support cell-mediated immunity. In phase 2, the function of CD8+ cytotoxic T cells is compromised. Virulent and cytopathic HIV strains then emerge, causing further loss of CD4 cells and ultimately death. Mounting evidence suggests that some people can resist or delay phase 2 — the long-term survivors. For example, some people are infected with HIV for more than eight years with no symptoms and CD4+ T-cell counts of >500 per cubic millimeter. Levy has found five major characteristics of long-term survivors, but such a complex combination of viral and host factors is not amenable to a simple analysis.

Levy states that the Concorde study did not show that 3'-azido-3-deoxythymidine, or zidovudine (AZT), prolongs life and cites a quality-of-life study showing that “a major benefit of AZT was not substantiated.” These statements reveal his pessimism regarding current therapies. His conclusion that “during asymptomatic infection, the presence of side effects and a lack of long-term benefits do not support [AZT's] use” is arguable. It is clear that AZT has clinical benefit. The real dilemma is when to start treatment and what combinations are best.

This comprehensive, well-written book should appeal to investigators at many levels of expertise. It will provide valuable background information and new directions for research on HIV and AIDS.

Howard E. Gendelman, M.D.
Susan Swindells, M.D.
University of Nebraska Medical Center, Omaha, NE 68198-5215