Summary: Defective regulatory components of the immune system seem to contribute to HIV disease progression. Highly active antiretroviral therapy (HAART) was reported to restore malfunctioning immunologic regulatory components. To corroborate this hypothesis, we studied different dendritic-cell (DC) and T-cell subsets with regulatory phenotype in 41 clinically stable patients with hemophilia more than 25 years after infection with HIV and 10 years after initiation of HAART. Compared with healthy controls, patients showed normal DC1 and DC2 levels, increased CD8+ peripheral blood lymphocyte (PBL) counts and T helper (Th) 2 proportions, and decreased Th1, CD3+CD4+CD127+, and CD3+CD8+CD127+ PBL proportions. High viral load was associated with high DC1, whereas high CD8+ PBL counts were associated with low DC2. CD3+CD4+CD25+Foxp3+ (regulatory T [Treg] cell) and CD3+CD8+CD28−Foxp3+ PBL counts (suppressor T [Ts] cell) exhibited normal levels in patients with undetectable retroviral load, were increased in parallel to retroviral load, and were associated with low CD8+ T lymphocytes and low CD19+ B lymphocytes. Normal or even increased levels of DCs and normal or even increased levels of PBL with a Treg or Ts phenotype that coincide with viral load increases and CD8+ T- and CD19+ B-lymphocyte decreases suggest a functioning immunoregulatory system that reacts to HIV replication. Increased CD8+ PBL counts imply immunocompetence. Increased CD8+ PBL counts and normal or even upregulated immunoregulatory cells might stabilize our long-term HIV-infected patients with hemophilia clinically.