Infrequent detection of HIV-1-specific, but not cytomegalovirus-specific, CD8(+) T cell responses in young HIV-1-infected infants

Early potent combination antiretroviral therapies (ART) for HIV-1 infection can preserve or restore immune function, but control of viral replication early in infection may interfere with the development of HIV-1-specitic imm une responses. Using an IFN-gamma ELISPOT assay, ive evaluated the breadth and intensity of HIV-1-specific CD8(+) T cell responses in 17 vertically in fected infants who began ART at 1-23 mo of age. CW-specific responses were also characterized in three infants coinfected with HIV-1 and CMV. Before A RT, HIV-1-specific CD8(+) T cell responses were detected in two of 13 (15%) infants <6 mo of age. HIV-1-specific CD8(+) T cells became undetectable in these two infants after the control of viral replication. Intermittent HIV -1-specific responses were noted in six infants who did not experience dura ble control of viral replication. In contrast, HIV-1-specific responses wer e detected before ART in four of four infants >6 mo of age and became persi stently undetectable in only one child. CMV-specific CD8(+) T cell response s were persistently detected in all HIV-1 and CMV coinfected infants. In co nclusion, HIV-1-specific CD8(+) T cell responses were less commonly detecte d before therapy in young infants than in older infants. Suppression of vir al replication appeared to interfere with the development and maintenance o f HIV-1-specific CD8(+) T cell responses. The detection of CMV-specific res ponses in HIV-1 and CMV coinfected infants suggests a selective defect in t he generation or maintenance of HIV-1-specific CD8(+) T cell responses. The rapeutic HIV-1 vaccine strategies in young infants may prolong the clinical benefit of ART by expanding the HIV-1-specific CD8(+) T cell pool.