Unmasking the Power of the Pediatric Immune System

Research question
Scientists know that HIV reservoir cells persist indefinitely in individuals on antiretroviral therapy (ART) who acquired HIV as adults. But what happens to the reservoir in people on long-term ART started during infancy?

In the early days of the AIDS pandemic, perinatal (mother-to-child) HIV transmission was widespread, with measures to prevent such infections not available in many resource-poor countries. This led to generations of adolescents and young adults who had initiated antiretroviral therapy (ART) in early infancy, with many remaining on effective treatment for over two decades. Yet little is known about how the pediatric immune system might suppress, or even eliminate, HIV reservoir cells in such individuals.

Findings
The researchers studied two fraternal twins born of a mother with HIV who had not received perinatal care. The twins were given AZT from birth to age six weeks, but at that point evidence of HIV infection was documented. Beginning at week 10, both received combination ART, with HIV suppression maintained for 28 years.

At that point the male twin was negative for anti-HIV antibodies and had only one isolate of intact HIV provirus—the latent form of HIV with the capacity to form fully infectious HIV—identified. The female twin had no detectable intact provirus. This profound decline in the frequency of intact HIV proviruses—a 4,000- to 13,000-fold drop over almost three decades—contrasts to a typical 10-fold decline over a similar period characteristic of adults on ART.

The researchers hypothesized that infants may be able to mount more effective immunologic targeting and elimination of cells harboring intact HIV proviruses. As precedent, they note the improved activity of the pediatric immune system against other viruses, most notably SARS-CoV-2, the viral cause of COVID-19.

Impact
The authors conclude that “[u]nderstanding how the pediatric immune system recognizes, targets, and eliminates HIV reservoir cells remains an important scientific question with marked public health implications.”

amfAR’s role
amfAR was a funder of this research. amfAR grantee Xu G. Yu, MD, of the Ragon Institute of MGH, MIT and Harvard, is one of the co-authors of the paper.

Original article
http://www.ncbi.nlm.nih.gov/pubmed/39541163

Dr. Laurence is amfAR’s senior scientific consultant.

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