Recent studies have suggested greater HIV cure potential among infected children than adults. A major obstacle to HIV eradication in adults is that the viral reservoir is largely comprised of HIV-specific cytotoxic T lymphocyte (CTL) escape variants. We here evaluate the potential for CTL in HIV-infected slow-progressor children to play an effective role in "shock-and-kill" cure strategies. Two distinct subgroups of children were identified on the basis of viral load. Unexpectedly, in both groups, as in adults, HIV-specific CTL drove the selection of escape variants across a range of epitopes within the first weeks of infection. However, in HIV-infected children, but not adults, de novo autologous variant-specific CTL responses were generated, enabling the pediatric immune system to "corner" the virus. Thus, even when escape variants are selected in early infection, the capacity in children to generate variant-specific anti-HIV CTL responses maintains the potential for CTL to contribute to effective shock-and-kill cure strategies in pediatric HIV infection.
J Exp Med
3239 - 3261
Adult, CD8-Positive T-Lymphocytes, Child, Child, Preschool, Epitopes, T-Lymphocyte, HIV Infections, HIV-1, HLA Antigens, Host-Pathogen Interactions, Humans, Immune Evasion, Interferon-gamma, T-Lymphocytes, Cytotoxic, Viral Load, gag Gene Products, Human Immunodeficiency Virus