Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-infected infants and children.

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 heterogeneous 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 x 10(4) to >10(6) 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 x 10(6)/L (<6.5 years of age) or greater than 200 x 10(6)/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.