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Quantification of CD4 Recovery in Early-Treated Infants Living With HIV
Juliane Schröter1, Anet J N Anelone1,2, Rob J de Boer1
1Theoretical Biology & Bioinformatics, Utrecht University, Utrecht, the Netherlands; and.
Insights
Early antiretroviral treatment helps infants with perinatal HIV regain normal immune function. Children starting treatment within six months achieve significant CD4+ T-cell recovery, indicating successful immune reconstitution.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Perinatal HIV infection can impair immune development in infants.
- Early antiretroviral treatment (ART) initiation is crucial for maintaining or restoring immune function.
- Prompt ART allows for near-normal immune development in HIV-exposed infants.
Purpose of the Study:
- To mathematically model and quantify CD4+ T-cell reconstitution in infants with perinatal HIV.
- To assess the impact of early ART initiation (within 6 months) and sustained viral suppression on immune recovery.
- To analyze factors influencing CD4+ T-cell recovery dynamics, including age and initial CD4+ T-cell counts.
Main Methods:
- Mathematical modeling was used to quantify individual CD4+ T-cell reconstitution.
- A subset of 276 children initiating ART within 6 months of age and achieving viral suppression was analyzed.
- A linear model approaching an asymptote was fitted to CD4+ T-cell data, accounting for age-related differences.
Main Results:
- Depleted CD4+ percentages (CD4%) and CD4+ counts (CD4ct) restored to healthy levels post-treatment.
- CD4+ T-cell counts recovered at a median rate of 4 cells/µL/day, with faster recovery in those with lower initial counts.
- CD4+ T-cell recovery was positively correlated with viral suppression and typically stabilized within 3-13 months after ART initiation.
Conclusions:
- Early ART in perinatally HIV-infected infants leads to significant CD4+ T-cell recovery.
- Sustained viral suppression is key to achieving near-complete immune reconstitution.
- CD4+ T-cell depletion is generally mild in early-treated infants, allowing for substantial recovery of T-cell numbers.
Background:
Perinatally HIV-acquired infants benefit from an early antiretroviral treatment initiation. Thanks to a short viral exposure time, their immune system can be maintained or reconstituted, allowing a "normal" immune development.
Methods:
In this study, we mathematically modeled and quantified individual CD4+ T-cell reconstitution of a subset of 276 children who started treatment within 6 months of age and achieved sustained viral suppression. Considering natural age differences in CD4+ T-cell dynamics, we fitted distances to age-matched healthy reference values with a linear model approaching an asymptote.
Results:
Depleted CD4+ percentages (CD4%) and CD4+ counts (CD4ct) restored healthy levels during treatment. CD4ct recovered with a median rate of 4 cells/µL/d, and individual recovery rates were correlated negatively with their initial CD4ct. CD4 values at onset of treatment decrease with age, whereas recovery times and levels seem to be age-independent. CD4 recovery correlates positively with viral suppression, and the stabilization of CD4 levels usually occurs after viral suppression. CD4 levels stabilize within 3-13 months after treatment initiation. The recovery dynamics of the CD4% is comparable with those of the CD4ct.
Conclusions:
In early-treated children with successful viral suppression, the CD4 depletion is typically mild and CD4+ T cells tend to "fully" recover in numbers.
