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 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, 5x10(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 log(10) 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 10 000 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 log(10) plasma RNA and relative risk of disease progression strongly supports therapeutic efforts to achieve plasma virus levels as low as possible.