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Pediatric AIDS prognosis using somatic growth velocity
V J Carey1, F H Yong, L M Frenkel
1Channing Laboratory, Harvard Medical School, Boston, Massachusetts 02115, USA.
Insights
Growth velocity deficits are common in children with human immunodeficiency virus (HIV) infection. Slower growth predicts a higher risk of death in pediatric AIDS patients, offering a simple prognostic tool.
Area of Science:
- Pediatric infectious diseases
- Growth and development in immunocompromised children
- Biostatistics in clinical trials
Background:
- Children with human immunodeficiency virus (HIV) infection often experience impaired somatic growth.
- Establishing normative growth velocity data is crucial for monitoring disease progression and treatment efficacy.
Purpose of the Study:
- To establish age-specific growth velocity norms for HIV-infected children.
- To evaluate the prognostic value of these growth velocity norms in predicting outcomes.
Main Methods:
- Pooled data from 1338 HIV-infected children (3 months to 15 years) across four US clinical trials.
- Calculated growth velocity distributions using statistical smoothing and quantile regression.
- Derived age- and sex-corrected z-scores for growth velocity.
Main Results:
- HIV-infected children exhibited significant deficits in height and weight velocity compared to reference standards.
- Approximately 33% of height and 20% of weight velocities fell below the third percentile, indicating growth failure.
- Both height and weight velocity significantly predicted mortality risk in children with AIDS, independent of other factors.
Conclusions:
- Normalized growth velocities serve as informative and cost-effective prognostic markers for pediatric AIDS.
- The presented growth velocity distributions can benchmark new therapeutic strategies against established antiretroviral treatments.
Objective:
To describe the natural history of somatic growth in HIV infection by constructing age-specific growth velocity norms and to assess specific prognostic information available using these norms.
Design:
Observations on 1338 HIV-infected children aged 3 months to 15 years who participated in one of four US clinical trials of pediatric anti-HIV therapies were pooled; baseline growth velocity data were obtained using the first 6 months of observation for each child.
Methods:
Distributions of physical growth velocities in HIV-infected children in the Pediatric AIDS Clinical Trials Group were computed. Statistical smoothing of growth histories was employed to derive velocity estimates, and quantile regression analysis of growth velocities was performed to allow comparisons of growth rates in age- and gender-heterogeneous cohorts in the context of HIV infection. The quantile regressions provide corrected z-scores for growth velocity that appropriately compare HIV-infected children with one another for the purpose of distinguishing more from less favorable prognoses.
Results:
Consistent deficits in growth velocity amongst HIV-infected children were revealed when compared with the Fels Institute velocity standards. Approximately 33% of height (and 20% of weight) age- and sex-corrected velocity measurements obtained in the first 6 months of clinical trial participation lay beneath the corresponding third percentiles of the Fels reference distributions, which are commonly regarded as critical indicators of growth failure. Proportional hazards regression tests indicated that both weight and height velocity contributed significant information on the risk of death among children with AIDS after adjusting for antiretroviral therapy received, CD4 cell counts, and age at trial enrollment. Comparing subjects who differ in initial weight velocity by one age- and sex-corrected SD, the relative hazard of death was 0.63 (95% confidence interval, 0.55-0.72; P < or = 0.0001) in favor of the child with greater weight velocity, controlling for antiretroviral therapy received, age and CD4 cell count at baseline. The analogous hazard ratio for height velocity was 0.68 (95% confidence interval, 0.57-0.79; P < or = 0.0001).
Conclusions:
Suitably normalized growth velocities are informative and inexpensive criteria for pediatric AIDS prognosis; the growth velocity distributions presented will be useful for comparing growth effects of new therapeutic strategies to those of single and combination antiretrovirals employed for maintenance of pediatric HIV infection in the mid-1990s.