HIV-1 viral load and CD4 cell count in untreated children with vertically acquired asymptomatic or mild disease.

Background: Plasma HIV-1 RNA levels are high in vertically infected infants. Information in older children is limited, particularly in those who have not received antiretroviral therapy. Objectives: To describe the relationships between HIV-1 RNA, age and CD4 cell count in untreated vertically infected children. Design: HIV-1 RNA was measured in 70 children [median age, 3.5 years (range, 0.4-11.9 years); median CD4 cell count, 881 x 10(6)/l (interquartile range, 576-1347 x 10(6) cells/l)] enrolled in a randomized placebo-controlled trial comparing immediate with deferred zidovudine in asymptomatic or mildly symptomatic vertically infected children (PENTA-1 trial). Short-term variability was assessed by comparing HIV-1 RNA at -2 and 0 weeks (prior to randomization). The relationship between age and HIV-1 RNA, and CD4 cell count was analysed using data from all children prior to randomization and sequential samples from 35 remaining on placebo for up to 105 weeks, by fitting mixed linear models. Results: The within-individual SD in viral load was 0.26 log(10) copies/ml. The median plasma HIV-1 RNA at enrolment was 4.61 log(10) (range, 2.3-6.56 log(10) copies/ml), significantly higher in children aged less than or equal to 2 years (median, 5.23 log(10) copies/ml) than in those aged > 2 years (4.51 log(10) copies/ml; P < 0.0001). Mean HIV-1 RNA fell by 0.38 log(10) copies/ml per year up to 2 years of age, by 0.21 log(10) copies/ml per year from 2 to 4 years of age, and by 0.03 log(10) copies/ml per year from 4 to 6 years of age reaching a nadir of 4.25 log(10) copies/ml at 6 years. Mean log(10) CD4 cell count declined steadily with age and was not significantly correlated with HIV-1 RNA, although there was some evidence that the rate of log(10) CD4 cell decline was negatively correlated with the initial rate of HIV-1 RNA decline. No mutations associated with resistance to zidovudine were observed. Conclusions: Age is a key factor in the interpretation of both viral load and CD4 cell count in vertically infected children.