Antiretroviral treatment in HIV-infected infants and young children: novel issues raised by the Mississippi baby

Abstract

The recent case report of an HIV-infected child in Mississippi with viral control post-antiretroviral therapy (ART) interruption has sparked interest in the possibility of ‘functional cure’ in infants if they initiate ART very soon after birth. The ‘Mississippi baby’ also raises many new questions around the clinical care of HIV-infected infants and young children, including when treatment should be initiated, why treatment should be initiated, what treatment should be initiated, and how to identify infants early enough to treat them adequately. Here, we review research conducted before the report of the ‘Mississippi baby’ highlighting the important new issues that now need to be taken into consideration.

Keywords::

• antiretroviral treatment
• functional cure
• HIV
• infants
• viral reservoir

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• The recent case report of an HIV-infected infant with viral control postantiretroviral therapy (ART) interruption has sparked interest in the possibility of ‘functional cure’ in infants with ART initiated soon after birth.

• The Mississippi baby raises challenging new questions for the care and treatment of perinatally HIV-infected children.

• When should treatment be initiated – for example, should we initiate ART at 1 year of age, 6 weeks of age or at birth? Results from the children with HIV early antiretroviral (CHER) trial are largely uninformative about whether or not treatment should be started at birth or what the relevant window of time would be after birth diagnosis to initiate treatment.

• Why should treatment be initiated – what outcomes are we trying to achieve? The traditional goal of early ART initiation for children is to reduce mortality and morbidity, as well as to achieve normal growth and development and improve quality of life. We need to carefully consider what endpoints might be considered evidence of steps along the way to ‘functional cure’ justifying withdrawal of ART.

• What treatment should be initiated – what options do we have available for early treatment? The Mississippi baby was initiated at 30 h of life, raising unique challenges about the appropriate starting regimen, as limited options are available in this early window.

• How do we identify HIV-infected infants early enough to treat them adequately? If ART is to be initiated at birth, as seems to be advisable based on the Mississippi baby, then routine diagnosis will also need to shift to birth with point-of-care diagnostic tests being the only practical approach.