July 10, 2002
Dr. Autran summarized past and new work performed by her group in Paris on the correlates of a favorable prognosis in long-term non-progressors (LTNPs). She focused on that group to gain insight into what type of immunity might be necessary for a therapeutic vaccine to be successful in helping control HIV replications. They identified a cohort of 70 long-term non-progressors (defined as CD4+ T-cell counts greater than 600 for five years or more without therapy) and another control cohort of 50 HIV-infected patients who demonstrated progression of their HIV disease.
Studies of immunologic markers in these cohorts found an association between the intensity and diversity of CD8+ cytotoxic lymphocytes (CTLs) and protection against progression (key test involves an ELISPOT assay looking at gamma-interferon production induced by various antigens).
Another arm of the cell-mediated immunity that was examined was HIV-specific CD4+ Th1 lymphocyte levels and activity. High levels of HIV-specific CD4+ Th1 lymphocytes were identified as the best factor linked to protection in the long-term non-progressor cohort. Another key aspect of protection against progression could be the genetic status of the patient (i.e., CCR5 and HLA-B27 haplotypes) that has been previously identified as important in certain populations. Another possible factor providing protection could be humeral immunity (such as IgG2 antibody levels). Dr. Autran's group found that high levels of IgG2 antibody also afforded protection in the long-term non-progressor group.
When combinations of these factors were included in an analysis of what mix of immunologic and/or genetic markers seemed to be most associated with the long-term non-progressor status, the best protection was seen in patients with both high levels of HIV-specific CD4+ T-cells and IgG2 antibodies. An excellent question from the audience involved the potential for a different conclusion one might reach in this type of analysis if newly infected patients were compared to those with established infection.
The long-term non-progressors are an unusual group of patients (less than 5 percent of all HIV-infected patients) and what is needed is data about what would protect the newly infected patient from progression versus what may still be protecting long-term non-progressors. Dr. Autran concurred that more work is needed on both populations and that insights from those studies may influence the direction taken in the development of either preventative or therapeutic HIV vaccines.
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