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Paul E. Palumbo, MD; Claire Raskino, MSc; Susan Fiscus, PhD; Savita Pahwa, MD, PhD; Mary G. Fowler, MD; Stephen A. Spector, MD; Janet A. Englund, MD; Carol J. Baker, MD

JAMA. 1998;279:756-761.

Context.— Pediatric human immunodeficiency virus (HIV) infection has unique viral pathogenetic features that preclude routine extrapolation from adult studies and require specific analysis.

Objectives.— To evaluate the prognostic value of 2 key laboratory markers—plasma RNA and CD4⁺ lymphocyte count—for HIV disease progression in infants and children and to establish targeted values for optimal outcome.

Design.— Data from a cohort of 566 infants and children who participated in a randomized, placebo-controlled trial of nucleoside reverse transcriptase inhibitors (ACTG 152) were analyzed. The trial was conducted between 1991 and 1995 and enrolled a heterogenous cohort of antiretroviral therapy–naive children (age, 3 months to 18 years); patients had a median follow-up of 32 months.

Main Outcome Measures.— The trial clinical end points consisted of time to first HIV disease progression (growth failure, decline in neurologic or neurodevelopmental function, opportunistic infections) or death.

Results.— Baseline plasma RNA levels were high (age group medians, 5x10⁴ to >10⁶ copies/mL), and both baseline RNA and CD4⁺ lymphocyte count were independently predictive of subsequent clinical course. Risk reduction for disease progression between 49% and 64% was observed for each log₁₀ reduction in baseline RNA and was linear without suggestion of a threshold or age effect. Disease progression predictive power was enhanced by the combined use of plasma RNA and CD4⁺ cell count. Marker values of less than 10000 copies/mL for plasma RNA and greater than 500x10⁶/L (<6.5 years of age) or greater than 200x10⁶/L (>6.5 years) for CD4⁺ cell count were associated with a 2-year disease progression rate of less than 5%.

Conclusions.— Two key laboratory markers—plasma RNA and CD4⁺ lymphocyte count—are independent predictors of clinical course among HIV-infected infants and children. The linear, age-independent relationship between log₁₀ plasma RNA and relative risk of disease progression strongly supports therapeutic efforts to achieve plasma virus levels as low as possible.

From the Department of Pediatrics, University of Medicine and Dentistry of New Jersey, Newark (Dr Palumbo); Department of Biostatistics, Harvard School of Public Health, Boston, Mass (Ms Raskino); Department of Microbiology and Immunology, University of North Carolina, Chapel Hill (Dr Fiscus); Department of Pediatrics, North Shore University Hospital, New York University School of Medicine, Manhasset (Dr Pahwa); National Institute of Allergy and Infectious Diseases, Bethesda, Md (Dr Fowler); Department of Pediatrics, University of California, San Diego (Dr Spector); and Departments of Pediatrics and Microbiology and Immunology, Baylor College of Medicine, Houston, Tex (Drs Englund and Baker).

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