July 11, 2002
Dr. Nokta and colleagues from the ACTG conducted an immunologic substudy (5007) among subjects enrolled in ACTG 384 (preliminary results presented at this meeting in posters LbOr20A and LbOr20B). The data presented in this poster involves the association between numerous baseline immunologic parameters.
Seventy-eight patients were enrolled in the substudy (63 men and 15 women) with a mean pre-therapy CD4+ count of 307 cells/mm3 and mean RNA of 4.81 log. The immunologic studies utilized include measurements of thymic size (thymic index), CD4+ activation markers, CD4+ and CD8+ naive T-cell levels and T-cell apoptotic markers.
There was a statistically significant positive correlation between naive CD4+ and CD8+ T-cell levels and absolute CD4+ T-cell counts. There was a significant inverse correlation between the levels of CD4+ and CD8+ naive cells and the baseline viral load (p = 0.0006). There was a weak inverse relationship between the percentage of apoptotic CD4+ T cells and the CD4+ count (p = 0.04) and no relationship between the percentage of apoptotic CD4+ T-cells and viral load (p = 0.2). There was a positive correlation between the thymic index and naive CD4+ (p = 0.001) and naive CD8+ (p = 0.0025) T-cell counts and an inverse relationship between the thymic index and age. That inverse relationship has been noted consistently in other studies and is a factor in the debate about delaying the initiation of antiretroviral therapy. The thymic index had a significant inverse correlation with the viral load and CD4+ T-cell activation markers (p = 0.012) and a marginally significant positive correlation with the absolute CD4+ T-cell count (p = 0.046).
These observations make biologic sense and fit well with the current thinking about the relationship between the thymus and HIV infection. This interesting study, which looked at the baseline status of this cohort of patients, suggests that both thymic depletion and/or activation contributes to the decline in CD4+ T-cell levels and is a consequence of high levels of viral replication. We look forward to future data from this study examining the impact of potent antiretroviral therapy in these immunologic parameters.
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