1st International AIDS Society Conference on HIV Pathogenesis and Treatment Buenos Aires, Argentina - July 8-11, 2001

[ABSTRACT:] In a prospective and longitudinal study of infants born to HIV-positive women, the level and specificity of HIV-specific CTL responses was assessed. A surprisingly high percentage (> 90%) of uninfected infants in this cohort have strong HIV-specific CTL activity, with the majority of CTL responses being directed to HIV-1 IIIB envelope. In addition, approximately one third of the uninfected infants have responses to other HIV genes such as gag, pol, gp120, or nef. Since the envelope responses were found in infants less than 18 months of age, it was possible that the cytotoxic activity was antibody-dependent, utilizing maternal antibodies. However, although ADCC activity was present in uninfected infants, it declined over time consistent with the decay of maternal antibody, and ADCC activity did not correlate with the presence or absence of envelope directed CTL activity. Cell separation experiments indicate that the envelope cytotoxic activity is due to CD4⁺ CTL not CD8⁺ or CD16⁺ cells, although cytotoxicity directed to other HIV genes is mediated by classical CD8⁺ class I-restricted CTL. The recent introduction of effective antiretroviral therapy and elective caesarian section has coincided with a marked reduction in the frequency of these HIV-1 envelope CTL responses among exposed uninfected infants. This observation suggests that the reduction in maternal viral load and decreased risk of viral exposure during the perinatal period associated with elective caesarian section may affect the generation of the HIV-1 envelope CTL response, indicating it is likely to have been primed by exposure to replicating virus.

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