Background:  Following mother to child transmission (MTCT) of HIV-1, infants characteristically exhibit sustained high plasma viral load and a rapid progression of disease. In a longitudinal study, we previously demonstrated that HIV-1-specific CD8 cytotoxic T cells responses are commonly found in infants following MTCT, but appeared ineffective in reducing HIV-1 viral load, and did not affect survival. We performed additional studies designed to elicit the basis of the sustained viremia found following peripartum infection of infants.

Methods:  Plasma HIV-1 RNA viral loads were determined by a transcription-mediated amplification method and gag-specific polymerase chain reaction (PCR) was used to detect HIV-1 DNA in filter paper specimens collected within 48 hours of birth. Peripartum infection had negative assays at birth, with subsequent evidence of plasma viremia. CD4 and CD8 subsets were quantified in cryopreserved specimens. Ki67 and CD25 staining was used to quantify activation and cell cycle progression in these subsets. T-cell receptor (TCR) recombination excision circles (TREC) in peripheral blood mononuclear cells (PBMC) were quantified by real-time PCR. Interferon-gamma (IFN-γ) ELISpot was used to quantify HIV-1-specific CD8 T-cell responses, using peptides representing HIV-1 A and D subtype epitopes restricted by MHC-I alleles commonly found in East African populations. 

Results:  From >500 infants enrolled, 21 with peripartum-MTCT were identified with detectable plasma HIV-1 RNA at 1 month of age (mean 6.72 log₁₀ copies/mL), and at least 2 subsequent visits in the first year of life (3, 6, 9, or 12 months of age):  71% had their peak viral load at 1 month and 15 had evidence of HIV-1 specific cytotoxic T lymphocytes by 9 months of age. There was no correlation between CD8 T-cell responses and the magnitude and timing of subsequent reductions in viral load. Relative to values from adults, median PBMC TREC values were highly elevated at birth in both HIV-exposed but uninfected infants. At 6 months of age, infants infected peripartum had a higher fraction of Ki67⁺CD4⁺ cells than did 10 HIV-exposed but uninfected infants (p = 0.007, Mann-Whitney U test). Median TREC values changed little through the first 12 months of life, despite the sustained high HIV viral load.

Conclusions:  T-cell activation and the relatively high degree of thymopoeisis seen in infancy likely contribute to the sustained high-level HIV-1 viral load seen after MTCT, which is unimpeded by nascent cytotoxic T lymphocyte activity.