Abstract
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, 5×104 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
500×106/L (<6.5 years of age) or greater than 200×106/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.
