An Updated Look at Immune Reconstitution

Abstract

With antiretrovial therapy (ART), nurses are now seeing patients live longer and healthier lives. They have seen their immune systems reconstituted as evidenced by an increase in CD4 T cells. Diseases that were relentless in the beginning of the epidemic have been tamed. Often, patients respond so well to ART that they no longer require prophylaxis medications against some of the common opportunistic infections. Despite this good news, we know that more than half of our patients who begin ART will experience virologic failure after 2 years. For other patients, the benefits of ART seem to have an effect only on viral load and not on T cells, leaving this subgroup of patients still vulnerable to infection. Obviously, ART is not enough. We need to find ways to increase immune reconstitution. Many areas have been explored; therapeutic vaccines have been and are being developed, and drugs currently on the market for other reasons are being tested to see if they will assist in the reconstitution of the immune system (e.g., growth hormones). One drug that has long been used toward this end is interleukin-2 (IL-2). IL-2 is a naturally occurring cytokine that when produced by our bodies, regulates the proliferation and distribution of lymphocytes, including CD4 and CD8 T cells. Many studies using recombinant IL-2 have shown that IL-2 administered intermittently with ART has resulted in sustained increases in CD4 cell counts. IL-2 is given subcutaneously and does bring its own long list of side effects. This issue of JANAC contains a supplemental section featuring four articles on the important issue of immune reconstitution. The first article, “Immune Mechanisms in HIV Infection,” details an immune response in healthy individuals and how that system goes awry in the HIV-infected population. The second article, “Immune Restoration in Patients With HIV Infection: HAART and Beyond,” explains how highly active antiretroviral therapy (HAART) has affected our patients and their immune systems, both positively and negatively. The third article, “Interleukin-2, Where Are We Going?” gives a historical overview of IL-2 and its use in clinical trials. The last article, “Management of Adverse Effects Associated With the Use of Interleukin-2 in Patients With HIV Infection,” gives much needed insight into handling the very significant yet manageable side effects of treatment with IL-2. This supplemental section of JANAC is being offered because as HIV nurses, we feel that immune reconstitution—and IL-2, specifically—is a challenging, interesting, and rewarding part of our practice. IL2 has been in development for many years. As nurses caring for patients infected with HIV, it is important for us to call for a renewed interest in its use and push for its approval as a medication approved in HIV infection. At present, IL-2 is still in clinical trials sponsored by the National Institutes of Health (i.e., the Esprit Trial, which is a multinational effort). Individual researchers are also pushing for it, and we need to add our voices to those who feel IL-2 is a drug our patients need. Personally, I feel that the benefits outweigh the side effects, and there are many data to suggest with some certainty that it works in increasing the number and durability of T cells. I would like to thank Dr. Richard Sowell for his assistance in preparing the supplemental section contained in this issue. I would also like the thank the following individuals who graciously gave of their time to peer review these articles: Gene Bundrock, MS, RN, CCM; Donna Sabatino, RN, ACRN; Kathy Foley, RN, MS; Christine Balt, RN, FNP, ACRN; Salome Juethner, NP; Shean Marley, RN, ACRN; Karen Anderson, MSN, NP; and Tom Young, MS, NP.