OBJECTIVE: To analyse the effect of viral coinfections on immune reconstitution in HIV-1-infected children (textless 18 years) taking highly active antiretroviral therapy (HAART). METHODS: Absolute lymphocyte numbers of various subsets of CD8 T cells were measured. RESULTS: Prior cytomegalovirus (CMV) infection correlated with an increased number of CD8 effector T cells (i.e., CD45RA+CD27-) at baseline (CMV-seropositive versus CMV-seronegative patients; P = 0.009), as well as an increased state of T cell activation as defined by HLA-DR and CD38 expression. The expansion of effector CD8 T cells persisted over time, independent of the HIV response to HAART. Numbers of CD8 effector T cells were significantly higher in patients with CMV replication as reflected by persistent urinary CMV shedding and periodic CMV DNAaemia (P = 0.02). These patients also showed an increase in CMV-specific antibodies compared with those without CMV shedding (P = 0.007). The number of CMV-specific interferon-gamma (IFN-gamma)-producing CD8 T cells was lower in children who persistently shed CMV compared with those who did not (P = 0.02). In contrast, CMV-specific CD4 T cell responses were detected at similar levels in both groups. CONCLUSIONS: In HIV-1-infected children, CMV infection correlated with the outgrowth of CD8+CD45RA+CD27- effector T cells. Activation of the immune system by persistent CMV secretion resulted in increasing CMV-specific IgG and higher numbers of CD8 effector T cells. Despite these increases, the CMV-specific IFN-gamma-producing CD8 T cell response was diminished, which could explain the inability to suppress CMV completely in 41% of HIV-1-infected children.