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Published on: December 3, 2019
Immune activation and paediatric HIV-1 disease outcome
Julia M Roider1, Maximilian Muenchhoff, Philip J R Goulder
1aDepartment of Paediatrics, University of Oxford, Peter Medawar Building for Pathogen Research, Oxford, UK bHIV Pathogenesis Programme, The Doris Duke Medical Research Institute cKwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Insights
Pediatric HIV is changing, with more children living with HIV due to increased antiretroviral therapy (ART) access. Understanding immune activation in children is key to improving long-term outcomes and developing new treatment strategies.
Area of Science:
- Pediatric Immunology
- Virology
- Infectious Diseases
Background:
- The pediatric HIV epidemic is evolving, with reduced new infections but increased numbers of children living with HIV due to greater antiretroviral therapy (ART) access.
- Chronic inflammation and immune activation, even with ART, pose significant long-term challenges, particularly for children infected from birth.
Purpose of the Study:
- To explore the unique aspects of immune activation in pediatric HIV infection.
- To identify factors influencing immune activation and disease progression in children with HIV.
- To discuss potential novel strategies for managing long-term HIV consequences in children.
Main Methods:
- Review of current literature on pediatric HIV infection and immune responses.
- Analysis of immune ontogeny and its interaction with HIV.
- Comparison of pediatric HIV infection phenotypes with adult non-progressing infection.
Main Results:
- Immune ontogeny in early life naturally favors lower immune activation, contrasting with factors in pediatric HIV that tend to increase it.
- A subset of ART-naïve children with HIV demonstrates non-progressing disease with normal CD4 counts despite high viremia and low immune activation.
- This pediatric non-progressing phenotype differs from adult non-progressing HIV, which is associated with specific HLA class I molecules and low viral load.
Conclusions:
- Natural immune processes in early life may offer opportunities for novel strategies to mitigate long-term HIV consequences in children.
- Understanding the mechanisms of low immune activation in natural HIV infection has broader implications beyond pediatric HIV management.
Purpose Of Review:
The paediatric HIV epidemic is changing. Over the past decade, new infections have substantially reduced, whereas access to antiretroviral therapy (ART) has increased. Overall this success means that numbers of children living with HIV are climbing. In addition, the problems observed in adult infection resulting from chronic inflammation triggered by persistent immune activation even following ART mediated suppression of viral replication are magnified in children infected from birth.
Recent Findings:
Features of immune ontogeny favour low immune activation in early life, whereas specific aspects of paediatric HIV infection tend to increase it. A subset of ART-naïve nonprogressing children exists in whom normal CD4 cell counts are maintained in the setting of persistent high viremia and yet in the context of low immune activation. This sooty mangabey-like phenotype contrasts with nonprogressing adult infection which is characterized by the expression of protective HLA class I molecules and low viral load. The particular factors contributing to raised or lowered immune activation in paediatric infection, which ultimately influence disease outcome, are discussed.
Summary:
Novel strategies to circumvent the unwanted long-term consequences of HIV infection may be possible in children in whom natural immune ontogeny in early life militates against immune activation. Defining the mechanisms underlying low immune activation in natural HIV infection would have applications beyond paediatric HIV.
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