Hi Tom,
Altho I am NOT adept at 'sleuthing', I think that I DID determine that Cel-Sci will not be presenting at the ICAAC.
However, from the URL that you provided, I was able to find some interesting abstracts. The site is 'search friendly' and having used Keywords from the Shareholder Letter AND the Univ. of Minnesota grant NR, I found some possible relevant papers:
Antiretroviral therapy intervention (from Shareholder Letter FAQ: HIV-AIDS)
39th ICAAC Program On-Line
Session: Strategic Approaches to Antiretroviral Therapy
Session Date: Tuesday, 9/28/99
Session Time: 2:00 pm - 4:30 pm
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"How Do We Exploit the Immune System?"
J.A. Levy
Univ. of California: San Francisco, CA
Infection with the human immunodeficiency virus (HIV) causes a compromise in immune function resulting primarily from direct infection of cells of the immune system, particularly CD4+ lymphocytes. In addition, cells of the brain, bowel, kidney, heart, and other tissues can be infected by the virus. The clinical course in infected individuals varies from a very rapid progression to disease as in infected newborn infants to a prolonged course in which some people are living more than 20 years with no signs of disease and on no antiviral therapy. The median time from infection to presentation with symptoms is about 10 years. A major reason that this infection can have variations in its expression of disease relates to the strength of the immune response against HIV. In long-term survivors, those living more than 10-15 years without symptoms and without therapy, a strong cellular immune response, particularly CD8+ cell non-cytotoxic immunity, can be demonstrated. This immunologic activity can be maintained for many years. It appears responsible for suppressing virus replication and keeping the immune system intact. Experimental evidence has demonstrated that the function of CD8+ lymphocytes depends on IL-2 principally made by CD4+ cells. Production of this cytokine is linked to normal functioning antigen presenting cells such as macrophages and dendritic cells. Thus attempts to maintain the immune response against HIV or to restore it to normal function should to be approached through immune modulation procedures. Other studies have demonstrated that individuals on long-term antiretroviral therapy show a decrease in CD8+ cell immune responses, and in some cases anti-HIV antibody production. These findings most likely reflect a decrease in viral antigen production under therapy. In attempts to restore immune responses in both infected and treated individuals, approaches including IL-2 administration and immunization are being explored. Essentially, the basic approach to maintaining long-term control of HIV, as seen in the long-term survivors, is linked to maintenance of strong CD8+ cell antiviral responses. Efforts to induce this response and sustain it in infected individuals should be encouraged.
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39th ICAAC Program On-Line
Session: Preservation and Enhancement of Immune System Responses in HIV Disease
Session Date: Monday, 9/27/99
Session Time: 8:30 am - 11:00 am
Presentation Time: 8:30 am - 8:45 am
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Clinical Impact of Treatment of Primary HIV-1 Infection with Zidovudine, Lamivudine, and Indinavir: a Cohort Study
M.M. Berrey1, T.S. Schacker2, A.C. Collier1, T. Shea1, S.J. Brodie1, R. Coombs1, L. Corey3
1Univ. Washington: Seattle, WA; 2Univ. Minnesota: Minneapolis, MN; 3Univ. Washington & Fred Hutchinson Cancer Res. Ctr.: Seattle, WA
Background: While antiretroviral treatment of primary HIV-1 is advocated, little data exist on its clinical benefit. Results: Standardized enrollment and follow-up procedures have been used in our acute HIV-1 infection clinic since its inception in 1993, allowing comparison of the clinical course of 67 subjects enrolled within 90 days of HIV-1 infection. 20 subjects were begun on zidovudine 300mg/d, lamivudine 300mg/d, and indinavir 2400mg/d; 47 subjects were initially untreated. Demographic and clinical parameters at enrollment were comparable for the two cohorts. Treated subjects achieved plasma HIV-1 RNA levels <500 copies/mL by week 7 and <50 copies by week 19. Treated subjects' absolute CD4+ T-cell counts increased 7.4 cells/month, while initially untreated subjects lost 9.6 cells/month (p=0.001). Twenty CDC defined Class B or C opportunistic infections (esophagitis, thrush, OHL) occurred in 10 (21.30%) initially untreated subjects, versus one (5%) of the initially treated cohort (one subject who had discontinued therapy). In an intent-to-treat analysis, an overall reduction of 90% (RR=0.11, p=0.02) in OIs was observed for the early treatment group. Six initially untreated subjects developed AIDS by CD4 counts <200/dL during the first 78 weeks of HIV-1 infection, versus none of the early treatment cohort (p<0.04). Treated subjects also had an 80+% reduction in mucocutaneous conditions (VZV, seborrheic dermatitis, psoriasis, gingivitis, others) (RR=0.17, p<0.001) and a 70+% reduction in respiratory infections (pneumonia, sinusitis, bronchitis) (RR=0.27; p<0.01). Conclusions: Early initiation of combination antiretroviral therapy reduced viral burden and improved CD4+ T-cell counts. There was a substantial 90% reduction in CDC-defined opportunistic infections and progression to AIDS within the first 78 weeks of HIV-1 infection. Less classically considered respiratory and mucocutaneous conditions were reduced by 70-80% in the early therapy cohort. Long-term monitoring will be necessary to determine whether initiation of therapy during primary HIV-1 infection results in sustained clinical benefit.
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