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Background: In the pre-HAART era, children positive for both CMV and HIV-1 were more likely to have disease progression than children who were HIV-1-positive but CMV-negative. In a healthy pediatric cohort it was shown that CMV infection was associated with the outgrowth of CD8⁺CD45RA⁺CD27^– effector T cells. In this study, we analyzed the effect of CMV infection and replication on CD8⁺ T-cell differentiation, as well as CMV-specific immunity in HIV-1-infected children under HAART.

Methods:   We followed prospectively 52 children, median age 5.0 years (range 0.8 to 17.9), starting HAART between 1997 and 2002. Immunophenotyping, CMV-serology, and CMV culture were performed at 3 monthly intervals. IFN-g production in response to CMV antigens was measured cross-sectionally.

Results:  Prior CMV infection correlated with an increased number of CD8⁺ effector T cells (i.e. CD45RA⁺CD27^–) at baseline (369 vs 101 cells/µL (CMV-seropositive (n = 37) vs seronegative patients (n = 15), respectively); p = 0.01), as well as an increased state of T-cell activation as defined by HLA-DR and CD38 expression. After 48 weeks, 44 children still had undetectable HIV RNA. The expansion of CD8⁺ effector T cells persisted after 48 weeks (323 vs 41 cells/µL), independently of the HIV response to HAART. Numbers of CD8⁺ effector T cells were significantly higher in patients with CMV replication (n = 13), as reflected by persistent urinary CMV shedding after > 36 weeks on HAART and periodic CMV DNA-emia, compared with those without CMV shedding (n = 19)(650 vs 270 cells/µL; p = 0.01). These patients also showed an increase in CMV-specific antibodies (73.3 vs 0.0 arbitrary units; p = 0.02). The number of CMV-specific IFN-g-producing CD8⁺ T cells was lower in children who persistently shed CMV compared with those who did not (6.1 vs 13.6; p = 0.02). In contrast, CMV-specific CD4⁺ T-cell responses were detected at similar levels in both groups.

Conclusions:  Our findings demonstrate that, in HIV-1-infected children CMV infection correlates with the outgrowth of CD8⁺ effector T cells (i.e. CD45RA⁺CD27^–). Chronic activation of the immune system by persistent CMV secretion resulted in increasing CMV-specific IgG and numbers of CD8⁺ effector T cells. Despite these increases, CMV-specific IFN-g-producing CD8⁺ T-cell responses are diminished.

Keywords: Pediatric HIV; CD8+ effector T cell; cytomegalovirus