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Very early combination antiretroviral therapy in infants: prospects for cure
Kaitlin Rainwater-Lovett1, Katherine Luzuriaga, Deborah Persaud
1aDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland bProgram in Molecular Medicine, Department of Pediatrics, and Center for Clinical and Translational Science, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Insights
Very early treatment (VET) in infants with perinatal HIV infection may lead to sustained remission. This approach appears to reduce the latent HIV reservoir, potentially delaying viral rebound and aiding HIV cure research.
Area of Science:
- Pediatric Infectious Diseases
- Virology
- Immunology
Background:
- The latent HIV reservoir is a major obstacle to achieving a functional cure for HIV.
- Initiating combination antiretroviral therapy (cART) earlier in life is associated with a smaller HIV reservoir size.
- A unique case (the "Mississippi child") demonstrated sustained HIV control after early cART in a perinatally infected child.
Purpose of the Study:
- To review the rationale and feasibility of very early treatment (VET) for achieving sustained virologic remission in perinatally HIV-infected children.
- To examine the impact of VET on biomarkers of HIV persistence in pediatric populations.
- To discuss the implications of VET for HIV cure research in children.
Main Methods:
- Case study analysis of a perinatally HIV-infected child who received VET.
- Review of recent studies on the effects of VET on HIV reservoir size and viral load in neonates.
- Analysis of biomarkers associated with HIV persistence in pediatric HIV infection.
Main Results:
- Sustained HIV control was observed in the case child for 18 months off antiretroviral therapy.
- VET initiated in neonates may significantly reduce latent replication-competent HIV reservoirs.
- Earlier treatment initiation correlates with smaller reservoir size and potentially longer remission periods.
Conclusions:
- VET represents a promising strategy for achieving sustained virologic remission in perinatal HIV infection.
- Reducing the latent HIV reservoir through VET is critical for HIV cure research in pediatric populations.
- Further research is needed to understand the long-term implications and challenges of VET for HIV cure.
Purpose Of Review:
A single case of sustained HIV control in the absence of antiretroviral therapy or HIV-specific immune responses ensued following 18 months of combination antiretroviral therapy initiated at 30 h of age in a perinatally HIV-infected child (the Mississippi child). This case provides proof-of-concept that delay in HIV viremic rebound may ensue following very early treatment (VET) in perinatal infection, likely through marked reduction of latent replication-competent HIV reservoirs.
Recent Findings:
The latent HIV reservoir remains the critical barrier to remission. Several studies indicate that the earlier effective combination antiretroviral therapy is initiated, the smaller the size of the HIV reservoir. The unique ability of perinatally infected neonates to initiate VET at the time of birth maximizes the potential benefits of limiting latent reservoir size and permitting reservoir decay, likely lengthening the duration of remission and limiting the capacity for re-establishment of viremia.
Summary:
This article covers the rationale and feasibility of VET to achieve sustained virologic remission in perinatal infection. Recent studies highlighting the effects of VET on biomarkers of HIV persistence in perinatal HIV infection are reviewed as well as implications and challenges for cure research in pediatric populations.
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