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Age- and time-related changes in extracellular viral load in children vertically infected by human immunodeficiency
K McIntosh1, A Shevitz, D Zaknun
1Division of Infectious Diseases, Children's Hospital, Boston MA 02115, USA. mcintosh@al.tch.harvard.edu
Insights
Viral load in vertically HIV-infected children gradually decreases after age one. This decline continues over years, reaching adult levels by age five, aiding in understanding pediatric HIV progression.
Area of Science:
- Virology
- Immunology
- Pediatric Infectious Diseases
Background:
- High plasma or serum viral load is characteristic of vertically HIV-infected children in their first year of life.
- Limited data exists on viral load changes after the first birthday in this population.
- Understanding the natural history of extracellular virus is crucial for pediatric HIV pathogenesis, prognosis, and therapy.
Purpose of the Study:
- To describe the changes in serum viral load over time in vertically HIV-infected children after their first birthday.
- To correlate viral load trends with age and clinical outcomes.
- To provide insights into the natural history of pediatric HIV infection.
Main Methods:
- Serum RNA was quantified using reverse transcriptase-polymerase chain reaction (RT-PCR).
- Immune complex-dissociated p24 antigen was measured using enzyme-linked immunosorbent assay (ELISA).
- Measurements were taken over time in 48 unselected children, analyzing findings in relation to age and clinical outcome.
Main Results:
- A gradual reduction in HIV RNA values was observed with increasing age (slope of -0.21 log copy/ml/year, P < 0.001).
- This downward trend persisted across all degrees of immunodeficiency.
- Repeated HIV RNA measurements showed a consistent downward trend (mean slope -0.11, P = 0.007), with a more negative slope in younger children at baseline. P24 antigen levels were less predictable.
Conclusions:
- Viral load in vertically HIV-infected children, measured by RT-PCR, declines very gradually over time.
- Viral titers decrease from high levels at the end of the first year.
- By approximately 5 years of age, viral load reaches levels comparable to those seen in horizontally infected adults.
Background:
It is known that plasma or serum viral load is high in vertically HIV-infected children during the first year of life, but the changes in these titers after the first birthday have not been described. Information on the natural history of circulating extracellular virus will be useful in elucidating the pathogenesis of pediatric HIV infection and in using viral load measurement to guide prognosis and therapy.
Methods:
We measured serum RNA by reverse transcriptase-polymerase chain reaction and immune complex-dissociated p24 antigen enzyme-linked immunosorbent assay over time in 48 unselected children followed in our clinics and analyzed the findings in relation to age and clinical outcome.
Results:
In first-available samples from the 48 children there was a gradual reduction in HIV RNA values with increasing age, with a slope of -0.21 log copy/ml/year (P < 0.001, R2 = 0.6022). This downward trend was seen in subsets of children with all degrees of immunodeficiency. The mean slope of repeated HIV RNA measurements in individual children was similarly in a downward direction (slope -0.11 (P = 0.007 for difference from zero)). The slope was more negative in children who were younger at baseline. Immune complex-dissociated p24 antigen values were much less predictable and predictive.
Conclusions:
Viral load in vertically infected children, measured by reverse transcriptase-polymerase chain reaction, falls very gradually over time, descending from very high titers at the end of the first year, and reaching values seen in horizontally infected adults at approximately 5 years of age.