Chapter 30 : Immune Intervention in AIDS

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This chapter reviews concepts and strategies that are being considered for the development of effective immune interventions for the treatment of human immunodeficiency virus (HIV) disease. It is likely that the development of effective immune-based interventions for the treatment of HIV infection will be greatly facilitated by an improved understanding of the fundamental mechanisms of the immunopathogenesis of AIDS. An important challenge for future research efforts will be to discover ways of modulating the host immune response so its beneficial aspects are enhanced without simultaneously increasing its deleterious aspects. Similarly, any attempt to use immunosuppression as an approach to abrogation of the deleterious indirect consequences of HIV infection will need to be done in a way that does not also compromise the beneficial aspects of immunemediated control of HIV replication. The idea of therapeutic vaccination of HIVinfected individuals dates back to the early years of the AIDS epidemic, and clinical trials aimed at augmenting anti-HIV cellular immune responses in infected patients by immunization with the recombinant HIV envelope glycoproteins gp120 and gp160 were first performed in the early 1990s. Recent studies of prophylactic DNA vaccine in macaque models of simian immunodeficiency virus (SIV) infection have shown that DNA vaccines, in combination with cytokines (e.g., interleukin-2 [IL-2]) or followed by boosting with recombinant viral vectors (e.g., an attenuated strain of vaccinia virus known as modified vaccinia Ankara), can induce potent anti-HIV CD4 and CD8 T-cell responses and enable substantial control of SIV viremia following experimental challenge with virulent virus strains.

Citation: Silvestri G, Feinberg M. 2002. Immune Intervention in AIDS, p 453-477. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch30
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Figure 1

Immunopathogenesis of HIV infection (A) in humans and SIV infection (B) in a natural host species (sooty mangabeys). Straight lines represent specific pathogenic mechanisms contributing to disease progression in chronically infected individuals. Dotted-bar lines represent physiologic (CTL) or therapeutic (HAART) events opposing the progression of the infection toward chronic immunodeficiency and AIDS. Dotted lines in panel B represent immunopathologic mechanisms of disease that are absent in the nonpathogenic chronic SIV infection of sooty mangabeys.

Citation: Silvestri G, Feinberg M. 2002. Immune Intervention in AIDS, p 453-477. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch30
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Figure 2

Virology and immunology in three subjects who controlled viremia after the first treatment interruption. In all three, the plasma viral load rose but then dropped, remaining consistently below 5,000 copies of HIV-1 RNA per ml (top row). Gag-specific T-helper-cell responses were maintained in all three subjects (middle row). CTL responses increased significantly from baseline values and are shown as responses to individual CTL epitopes with HLA restriction (bottom row). CTL responses were confirmed by cloning and testing in cytolytic assays. The shaded area indicates antiviral therapy reinitiated for subject 3, despite not meeting protocol indication for retreatment. Reprinted from with permission of the publisher.

Citation: Silvestri G, Feinberg M. 2002. Immune Intervention in AIDS, p 453-477. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch30
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Table 1

Mechanisms of immune evasion by HIV

Citation: Silvestri G, Feinberg M. 2002. Immune Intervention in AIDS, p 453-477. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch30
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Table 2

Immune interventions in HIV-infected individuals

Citation: Silvestri G, Feinberg M. 2002. Immune Intervention in AIDS, p 453-477. In Kaufmann S, Sher A, Ahmed R (ed), Immunology of Infectious Diseases. ASM Press, Washington, DC. doi: 10.1128/9781555817978.ch30

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