February 12, 2003
This session on immune-based therapy was very interesting but promised more than it delivered. All of the presentations prior to this one suffered from problems with trial design. The interferon study (Abstract 59) was too small in scope (n=5 each group) and the other two therapeutic vaccine pilot trials had no control group so that the claims of possible immunologic benefit were not well substantiated. For the ANRS 093 trial presented by Y. Levy, a control group not receiving vaccinations was used. Both groups received HAART for 40 weeks after entering the study. The vaccine group received two vaccines at weeks 0, 4, 8 and week 12 and then received IL-2 at 4.5 million units SC BID for five days at weeks 16, 24 and 32. Study subjects with viral loads less than 50 copies/ml at week 36 had HAART stopped at week 40. The endpoints were 1) viral load more than 50,000 at week 44 or more than 10,000 after week 48, and 2) lymphoproliferative response (LPR) to p24 and 11 other peptides.
The CD4 change at week 36 was +60 for the control group and +323 for the vaccine/IL-2 group (p=<0.001). The HIV RNA level was less than 50 copies for 86 percent of the control group and 97 percent for the vaccine/IL-2 group. Virologic success as defined as time to re-initiate HAART or time to peak viremia was higher in the vaccine/IL-2 group than in the control groups (42 days versus 29 days and 41.5 and 34 days respectively). The number of subjects in the vaccine/IL-2 arm with a sustained p24 LPR at weeks 16 and 24 and with LPR=1 HIV peptide was higher than in the control group (p=0.046 and 0.014 respectively). Logistic-regression analysis found that those immunologic parameters were predictive of HIV control at week 52.
This was the best designed study in this session. The use of IL-2 made it difficult to assess the impact of the two vaccines on the modest improvements in immunologic and virologic parameters. Also, the narrow and short-term definition of viral failure would not allow assessment of what happens during a longer period off therapy. Since there is often a brisk rebound in viremia when therapy is stopped, an important issue involves whether the viral set point is at a lower level in the group receiving the intervention. Nonetheless, this study did demonstrate modest virologic benefit associated with an enhanced polyepitopic HIV immune response due to a combined immunologic intervention (need to assess IL-2 and vaccination separately, as noted in one of the questions from the audience). This study is indicative of how the "old Europe" is managing to lead the way with fresh and innovative ideas and studies.
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