Vaccination of HIV-infected individuals increases HIV viral load, reduces CD4 cell counts, and might influence disease progression. Because these deleterious effects are postulated to be secondary to a direct activation of T lymphocytes induced by the immunogen, we compared immunologic and virologic effects of a T cell-dependent and a T cell-independent vaccine. Seventeen HIV-infected children were immunized with influenza (FLU) (T cell-dependent) or pneumococcal (PNEUMO) (T cell-independent) vaccines. HIV viral load and type 1 (IL-2 and IFN-gamma) and type 2 (IL-4 and IL-10) cytokine production were evaluated before and 7, 14, and 28 days after vaccination. Slopes of CD4 cell counts analyzed 6 months before and 6 months after vaccination were not significantly different. HIV viral load increased in both groups of children despite the fact that type 1 cytokine production and the type 1-to-type 2 ratio increased in FLU-vaccinated but not in PNEUMO-vaccinated patients. Thus, an increase in HIV viral load in the absence of T cell activation (as measured by cytokine production) was observed in PNEUMO-vaccinated children. Because polysaccharides of the bacterial cell wall stimulate TNF-alpha production by monocyte-macrophages and TNF-alpha was shown to stimulate HIV replication directly on activation of NF-kappa b after binding the long terminal repeat (LTR) sequences of HIV, we measured TNF-alpha production and observed a significant increase in both groups of vaccines. These data suggest that an increase in HIV viral load can be observed in vaccinated HIV-infected children even independent of direct antigen-induced activation of T lymphocytes, and that augmented production of TNF-alpha might play a role in this phenomenon.