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Background:  The role of HIV-specific T-cell responses in the control of viremia has not been well studied in children. It is not clear when HIV-specific T-cell responses become detectable in children or whether the responses are associated with improved immune control. Also, studies have not addressed the role of early HAART and structured treatment interruption (STI) in children. The Pediatric STI Study in South Africa is characterizing HIV-1-specific T-cell responses in acutely infected infants randomized onto early HAART and STI treatment arms.

Method:  We will enroll 60 acutely HIV-infected infants into the study, 20 children into 1 of 3 arms:  arm A, HAART onset as indicated by a low percentage of CD4 or clinical criteria; arm B, immediate HAART; Arm C, STI following immediate HAART. CD8⁺ and CD4⁺ T-cell responses are characterized using 410 peptides spanning the HIV clade-C consensus sequence on the IFN-γ ELISpot. Intracellular cytokine staining for IFN-γ, TNF-a, and IL-2 was also used to further characterize HIV-specific T-cell responses.

Results:  We have been enrolled 22 infants, 7 in arm A, 7 in arm B, and 8 in arm C. All children target the Nef/Tat/Rev/Vif/Vpu/Vpr (NTRVVV) region of HIV-1 the most, followed by Gag, Env, and then Pol. The CD8⁺ T-cell responses were detectable as early as week 1 in 3 infants. Children on arm A showed high CD8⁺ T-cell activity (100 to 2900 SFC/million PBMC). Responses that were detectable in arm B and C subjects before HAART initiation declined following onset of HAART. In arm C subjects, responses that became undetectable during HAART were detectable again following treatment interruption with additional epitopes targeted. Treatment interruptions were brief (2.5 weeks) in 2 of the subjects who have already undergone 2 treatment interruptions. 

Conclusions:  HAART reduced both viremia and T-cell responses in treated infants. The responses were augmented and broadened following exposure to antigen with treatment interruption. The entire HIV-1 genome was targeted with NTRVVV and Gag being targeted by most subjects, a similar pattern has been noted in adults. Low magnitude CD8⁺ T-cell responses were detected soon after birth. HIV-specific CD4⁺ T-cell responses were only observed exceptionally. The short interruption period could be due to a slow development of effective CD8⁺ T-cell responses in the first few months of life. The ongoing study will help establish the role played by CD8⁺ T-cell responses and the epitopes targeted during early infection in infants.

Keywords: CD8+ T cell response; CD4+ T cell response; HAART