Early antiretroviral therapy in HIV-infected infants: can it lead to HIV remission?

Abstract

Interventions to prevent mother-to-child HIV transmission have been extremely successful, but new HIV infections continue to occur in infants. Strong evidence indicates that combination antiretroviral therapy (ART) for treatment should be started in HIV-infected infants to prevent early morbidity and mortality. In 2013, the report of the Mississippi baby, who was started on ART within 30 h of life and maintained off-treatment remission for 27 months before HIV was once again detectable, generated renewed interest in very early ART initiation. The case stimulated interest in the possibility of HIV remission, which we define as maintenance of plasma viraemia below the threshold of detection in the absence of ART, after early treatment initiation. The possibility of HIV remission elicits much hope, given that children with HIV infection currently face a lifetime of treatment. The potential for early ART to lead to HIV remission in infants can be thought of in terms of six factors: rapidity of viral suppression with very early ART; initial viral suppression rate with early ART; later virological control after early treatment; the effect of early treatment on the viral reservoir size; outcomes of randomised trials of structured treatment interruption; and the likelihood of viral rebound in neonates after ART cessation. Review of existing data suggests that achieving long-term remission off treatment remains elusive, and concentrated attention and commitment of the scientific community is needed to investigate the factors that might help to reach this goal.

Figure 1:

Six questions developed to help inform whether early ART may be able to lead to HIV remission in some infants overlaid with the clinical trajectory of the Mississippi baby (13, 14).

Figure 2:

Published viral loads by age in months in neonates initiating combination antiretroviral therapy (N=13)

Figure 3:

Ecological study plot of median age at antiretroviral therapy (ART) initiation (months) and percentage with viral suppression at 6 months after starting treatment. Note: size of circle reflects size of study Notes: *Median age at ART initiation was estimated as the midpoint of the range; **Did not have 6 month suppression rate; ***Has children >12 mo

Figure 4:

Data from studies of infants and children comparing markers of the size of the viral reservoir in children who start treatment early and late Note: All cells are PBMCs except Martinez-Bonet, 2015 (65) (CD4+ T-cells)

Figure 5:

Time to HIV RNA viral rebound in days after treatment cessation in HIV-infected infants who initiated ART in the neonatal period and later stopped ART (N=5). Legend indicates the age at which the infant stopped ART.