Paediatric HIV infection: the potential for cure

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Abstract
Recent anecdotal reports of HIV remission in children following a discrete period of antiretroviral therapy (ART) have prompted the suggestion that HIV cure might be more readily achieved in children than in adults. This Review examines the evidence for such a claim and discusses the unique opportunities for immunotherapeutic interventions in children to maximize HIV cure potential. ART can be initiated within minutes of birth following in utero infection with HIV. Early initiation of ART results in a substantially smaller viral reservoir. The decay half-life of the viral reservoir is shorter following ART initiation in children compared with adults, and the decrease in size of the reservoir seems to continue for longer in children. The tolerogenic immune environment in utero and in early life increases the potential for HIV cure in infants. Other aspects of immune ontogeny, including the strong T helper 17 cell bias at birth, decrease cure potential in children. The overall balance between these opposing influences may depend crucially on the timing of initiation of ART. Maternal factors — including maternal health (which influences child feeding, general care and ART provision), maternally transmitted infections (such as cytomegalovirus and tuberculosis) and genetic factors (such as the effect of HLA class I alleles on dendritic cell function through leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) binding avidity) — could all markedly affect the potential for HIV cure in children. Paediatric infection presents particular opportunities for HIV cure through early interventions in addition to ART. Certain challenges are also posed by paediatric infection and the effects of immune ontogeny. The onset of puberty may limit the optimal window of opportunity for immunotherapeutic interventions in children to the ages of ∼3–9 years.

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