Role of HIV-specific CD8+ T cells in pediatric HIV cure strategies after widespread early viral escape.
Leitman EM., Thobakgale CF., Adland E., Ansari MA., Raghwani J., Prendergast AJ., Tudor-Williams G., Kiepiela P., Hemelaar J., Brener J., Tsai M-H., Mori M., Riddell L., Luzzi G., Jooste P., Ndung'u T., Walker BD., Pybus OG., Kellam P., Naranbhai V., Matthews PC., Gall A., Goulder PJR.
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.