More about Fauci's changing views: Fauci has finally acknowledge that anti-HIV specific immune responses will be required to treat and control HIV infection. Not only that, in the past Fauci and many others did not believe that the immune response could help control viral infection. Now Fauci says:
"In fact, although it was originally felt that the immune system could not undergo a substantial degree of spontaneous reconstitution during HIV infection, it is now clear that, in the era of HAART, varying degrees of improvement in immune system function are indeed possible."
Kind of what Jonas Salk said over 10 years ago.
"In addition to more effective and less toxic HAART regimens, including, perhaps, regimens of structured drug holidays, such a goal will almost certainly require a major contribution from host factors such as HIV-specific immune responses. A number of studies have been aimed at enhancing both HIV-specific and nonspecific immune responses by a variety of approaches, including intermittent infusions of immuno-enhancing cytokines such as IL-2, thymic transplantation, bone marrow transplantation, and, post-infection HIV-specific vaccination."
from: Latent Reservoirs of HIV: Obstacles to the Eradication of Virus.
Tae-Wook Chun, Ph.D. and Anthony S. Fauci, M.D.
niaid.nih.gov Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health Bethesda, Maryland. Proceedings of the National Academy of Sciences - Vol. 96, Issue 20, 10958-10961 September 28, 1999
"There has been considerable interest in potential approaches toward diminishing, containing, or eliminating the latent reservoir of HIV in infected individuals. Among such approaches is the preservation of normal HIV-specific immune function by early treatment of HIV infection before the development of significant virus-related immune dysfunction. Because a considerable proportion of patients begin treatment after substantial damage to the immune system has already occurred, this approach may not be feasible in most cases. Therefore, consideration has been given to the use of immune enhancers to partially reconstitute immune competency. To achieve this goal, the use of immune-activating reagents, such as anti-CD3 antibody, IL-2, and therapeutic HIV-specific vaccines has been considered."
"Initial attempts at utilizing anti-CD3 antibody in HIV-infected individuals who are receiving HAART have been somewhat discouraging because of the toxic nature of this reagent in vivo.
The use of intermittent IL-2 in infected individuals has been extensively studied and has resulted in considerable expansion of the pool of CD4+ T cells, despite manageable toxicity's during the period of administration."
(I think that means hospitalization, to manage the toxicity.)
"Many of these approaches had been attempted during the pre-HAART era, when adequate control of HIV replication was not attainable.
Now that prolonged suppression of HIV plasma is plausible, such adjunctive immune-based approaches might have a much higher probability of success. In this regard, the immune system may ultimately be capable of controlling the spread of virus from HIV reservoirs, as suggested in studies of HIV-infected individuals with long-term non-progressive disease in whom persistent HIV-1 specific CD4+ T cell responses have been demonstrated.......Of note, the regeneration of non-HIV-specific responses appears to occur much more readily than the regeneration of HIV-specific responses. Clearly, heightened emphasis on research on immune-based therapy directed toward the preservation and enhancement of HIV-specific immunity is warranted if long-term control and perhaps functional eradication of HIV are to be realized. Unfortunately, currently available regimens of HAART alone do not seem capable of achieving such a goal."
At one point, not that long ago, IL-2 was being heralded as a tool in the goal of eradicating HIV. Isn't it interesting that the media has paid no attention to the failure of IL-2 to purge the reservoirs of HIV? We all know what would happen to any biotech company that released this kind of news. I wonder if the NIH still going to fund that $40 million plus study of IL-2 plus HAART, a ten year multi-site study? I guess they want to establish the nature of the non-specific immune response.
This was the Immune Response citation:
Moss, R. B., Giermakowska, W. K., Savary, J. R., Theofan, G., Daigle, A. E., Richieri, S. P., Jensen, F. C. & Carlo, D. J. (1998) AIDS Res. Hum. Retroviruses 14, Suppl. 2, S167-S175.
Gulick, R. M., Mellors, J. W., Havlir, D., Eron, J. J., Gonzalez, C., McMahon, D., Richman, D. D., Valentine, F. T., Jonas, L., Meibohm, A., et al. (1997) N. Engl. J. Med. 337, 734-739.
|
