Immune Reconstitution: New Review on Web

"Immune Reconstitution and Immunotherapy in HIV Infection," an excellent one-hour overview of current knowledge about possibilities of immune-based therapy for HIV disease, went online last week on the Medscape site, http://www.medscape.com/hiv-aidshome; the author is Bruce D. Walker, M.D., of Massachusetts General Hospital and Harvard Medical School. Anyone can use this review without charge, and for medical professionals, one hour of continuing medical education credit is available. This module is written for "primary-care physicians, physician assistants, pharmacists, as well as specialists in AIDS care who seek a better understanding of host defenses against HIV and how these might be augmented to benefit patients." Readers will need some familiarity with basic immune-system concepts and terminology--for example humoral (antibody) vs. cellular immunity, CD4 T-helper cells, and CD8 CTLs (cytotoxic T lymphocytes). For those who want more in-depth information, over 130 references are included.

We believe that studying the immune system in HIV disease--and the possibility of therapy to help the immune system maintain control of the virus--is the most important area of AIDS treatment research today, but receives too little attention and funding because the money and institutional structures are focused on antiretrovirals. Dr. Walker is one of the most influential experts in this area. To give readers a quick overview of his review of this field, we quote the introduction, table on contents, and a paragraph on testing for HIV-specific immunity.


Introduction

"An understanding of the potential for immunotherapy and immune reconstitution in HIV infection requires a detailed understanding of the host immune response to this virus. Emerging data over the past 2 years indicate that the immune system plays a key role in determining the viral set point and delaying disease progression. There is no doubt that highly active antiretroviral therapy (HAART) has had a beneficial effect among infected persons,[1,2] but in the absence of the ability to eradicate latent virus, it is likely that the next big breakthroughs in HIV treatment will come through manipulation of the immune system. Therefore, this review begins with a detailed explanation of the way in which the body responds immunologically to chronic viral infections in general and to HIV in particular, and provides a description of the most important components of this immune response for containing the virus. Specific Immunotherapeutic strategies that are being pursued or planned will then be discussed."

Table of Contents
    Introduction
    Immune Protection in Chronic Viral Infections
    Immune Responses to HIV-1 Infection
    Immunologic Control of HIV Infection
      Cytotoxic T lymphocytes
      T-helper cell responses
      Neutralizing antibodies
      The special case of exposed seronegative persons
    Limits of Immunologic Control
      Immune exhaustion
      Lack of adequate T-helper cell function
      Immune escape
      Host genetic factors
      Direct infection of CD8 cells
    Immunologic Monitoring in HIV Infection
    Immune Reconstitution in the Era of HAART
      General immune function
      Thymic function
      HIV-specific immunity
      Immune recovery inflammatory syndromes
    Approaches to Immune-Based Therapy in HIV Infection
      Cytokine-based therapy
      Adoptive cell transfers
      Therapeutic vaccination
      Interruptions in therapy to augment immunity
      Passive antibody therapy
      Gene therapy
    Conclusions
    References
Tests of HIV-Specific Immune Function

Dr. Walker discusses new blood tests of how well the immune system is responding to HIV. Today these tests are used only by research specialists, but they could become more standardized and available--greatly accelerating research and development in immune-based therapies, as viral load testing did several years ago for the development of antiretrovirals.

"Tests of virus-specific immune function, including CTL assays, assays for T-helper-cell function, and neutralizing antibody responses, are not readily available. In fact, there are no standardized tests in existence for measuring HIV-1-specific immunity. These assays are only available through research laboratories, and different investigators employ different techniques for performing them. The field would greatly benefit from standardized, sensitive and highly reproducible assays. These are likely to be forthcoming now that new flow-cytometry-based assays are becoming available, and may be extremely important in monitoring clinical trials of immune-based therapies."


Taking the Course Online (Or Printing a Copy)

Medical professionals or others can take this one-hour course at http://www.medscape.com/hiv-aidshome; look under "Clinical Management." You can also print a copy to read elsewhere, directly through your browser with no other software required.

This program was sponsored by an unrestricted grant from Agouron Pharmaceuticals.