345 Lymphoproliferative Responses to HIVp24 in Chronically HIV-1 Infected Patients Treated with HAART Reflect Low-level Viral Replication but Not an Improvement in Indices of Immune Phenotype or Function C. G. Lange*1,2, B. K. Patterson3, B. Harnish4, K. Medvik1, Z. Xu4, R. Asaad1, H. Valdez1, S. J. Lee5, A. Landay6, J. Lieberman4, M. M. Lederman1 1Ctr for AIDS Res, Case Western Reserve Univ, Univ Hosp of Cleveland, OH; 2Med Clin, Res Ctr, Borstel, Germany; 3Childrenīs Mem Hosp, Northwestern Univ Med Sch, Chicago, IL; 4Ctr for Blood Res, Harvard Med Sch, Boston, MA; 5Dana-Farber Cancer Inst, Boston, MA; and 6Rush Med Coll, Chicago, IL
Background: While CD4+ T-cells may be needed to sustain CD8+ T-cell activity in chronic viral infection, it has been difficult to dissect the cause-and-effect relationship between preservation of CD4+ T-cell helper function and control of HIV-replication.
Methods: Functional immune responses to vaccination (immune response scores), lymphocyte phenotype and expression of cytolytic molecules on HIV-specific CD8+ T-cells, and levels of intracellular HIV-mRNA were analyzed in HIV-infected patients (pts) with HIV-RNA < 400 copies/mL for > 12 months, and strong (group A: stimulation index [SI] > 10) or absent (group B: SI < 3) lymphocyte proliferation (LP) to HIVp24 antigen. Group comparisons were analyzed by non-parametric Mann-Whitney tests. Proportions were estimated by Pearsonīs chi2 analysis.
Results: Mean SI in response to HIVp24 antigen was 20.0 and 1.4 in groups A (n = 21) and B (n = 18), respectively. Median circulating numbers (cells/muL) of CD4+ (705; 744) and CD8+ (963; 865) T-cells, CD28+/CD4+ (657; 698) and HLA DR CD38+/CD8+ (114; 93) T-cells and immune response scores to non-HIV antigens were comparable in both groups (0.47; 0.46). In a subgroup of HLA-A2+ or B8+ pts, HIV-reactive CD8+ T-cells in both groups had similar expression of perforin, granzyme A, and T-cell maturation markers (CD27, CD28, CCR7, CD62L). Pts with SI > 10 in response to HIVp24 had a higher frequency of CD4+ cells with intracellular HIV-1 mRNA (> 1.5%) than did pts with SI < 3 (p < 0.05).
Conclusion: Following longstanding suppression of viral replication on HAART, the presence of HIV-1 specific T-helper cell responses reflects low level HIV-1 replication, but there is no evidence that heightened CD4+ T-cell responses are related to improvements in indices of immune phenotype or function.
