Book Review

Immunology of HIV Infection

N Engl J Med 1997; 336:1533May 22, 1997

Article

Immunology of HIV Infection
Edited by Sudhir Gupta. 612 pp., illustrated. New York, Plenum, 1996. $95. ISBN: 0-306-45255-3

This book provides a comprehensive overview of most aspects of the immunology of human immunodeficiency virus (HIV) infection and AIDS. Of necessity, the literature surveyed in 30 chapters by international experts in the field fails to highlight spectacular research results reported in 1996, such as the identification of a herpesvirus in Kaposi's sarcoma, the identification of a novel coreceptor for HIV, and the dramatic decreases in HIV viral load with combination antiviral drug treatment. Nonetheless, this book contains a wealth of information for beginners and experts in the immunology of AIDS.

The book makes it painfully clear that we have not yet resolved such basic issues as why CD4+ helper cells decline over time or the extent to which HIV-specific cytotoxic T cells provide protection against HIV or promote the destruction of the immune system. Chapter 7, on apoptosis of lymphocytes in HIV infection, sums up the state of affairs: “Thus, even after one and a half decades of intensive studies, the exact mechanisms underlying HIV-mediated cytopathicity are still enigmatic and need closer scrutiny.”

Many of the chapters are well illustrated, but some would have benefited from better figures. For readers who are not experts on signal transduction, the discussions in chapter 4 (on lymphocyte adhesion coreceptors and their roles in the replication of HIV type 1) and chapter 6 (on the effects of HIV and HIV envelope glycoproteins on signaling pathways in T lymphocytes) make little sense without clarifying figures.

The section on immunotherapy dramatically shows how immune-based interventions in HIV infection and AIDS have failed so far. As with most other diseases, including cancer, cytokine treatment by itself is unlikely to have a substantial effect on AIDS. The chapter on HIV vaccines highlights the early preoccupation with envelope vaccines designed to induce neutralizing antibodies against HIV. Although theoretically capable of disease prevention, so far such antibodies can neutralize isolates of HIV that were adapted to T-cell lines but not natural field isolates of the virus. Even the question whether neutralizing antibodies can prevent sexual transmission of HIV has not been resolved. Will the next generation of vaccines be more successful? Novel vaccines are likely to be based on recombinant poxvirus, with broad representation of not only viral envelope genes but also the pol, gag, and nef genes of HIV, and they must be capable of inducing both neutralizing antibody and HIV-specific T cells. Such vaccines may be effective if they can induce cytotoxic T-lymphocyte responses before infection (prevention) or in patients with low viral loads after treatment with antiviral drugs.

I found the chapters on thymic hormones, growth factors, T-cell vaccination (i.e., vaccination against damaging but not beneficial T cells), and gene therapy detractions, because successful therapeutic applications in these areas appear to be far removed from reality, with the possible exception of supportive therapy with hematopoietic growth factors.

This book summarizes 13 years of immunologic research in HIV infection and underscores the immense complexity of the immunopathogenesis of AIDS and the futility of efforts to pinpoint the pernicious strategy this very old virus uses to subvert the human immune system. The book challenges its readers to search the evidence for important clues and new leads. The results may prove rewarding not only in the case of AIDS but also in the case of other immunopathologic conditions and cancer immunotherapy.

Cornelis J. Melief, M.D., Ph.D.
Leiden University Medical Center, 2300 RC Leiden, the Netherlands