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,
* Graduate Program in Immunology/Virology,
Department of Pediatrics, and
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605
This study investigated the relationship between HIV-1 replication and virus (HIV-1; CMV)-specific CD4+ T cell frequency and function in HIV-1-infected children. HIV-1 gag p55-specific CD4+ T cell IFN-
responses were detected in the majority of children studied. p55-specific responses were detected less commonly and at lower frequencies in children with <50 copies/ml plasma HIV-1 RNA than in children with active HIV-1 replication. In children with <50 copies/ml plasma HIV-1, p55-specific responses were detected only in children with evidence of ongoing HIV-1 replication, indicating a direct relationship between HIV-1 replication and HIV-specific CD4+ T cell frequencies. In contrast, p55-specific proliferative responses were detected more frequently in children with <50 copies/ml plasma HIV-1. CMV-specific CD4+ responses were more commonly detected and at higher frequencies in CMV-coinfected children with suppressed HIV-1 replication. The lack of HIV-specific CD4+ proliferative responses, along with the preservation of CMV-specific CD4+ responses in children with controlled HIV-1 replication, suggests that viral replication may have deleterious effects on HIV-1 and other virus-specific CD4+ responses. Vaccination to stimulate HIV-specific CD4+ T cell responses in these children may synergize with antiretroviral therapy to improve the long-term control of viral replication, and may perhaps allow the eventual discontinuation of antiretroviral therapy.
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