HIV-1 viral load and CD4 cell count in untreated children with vertically acquired asymptomatic or mild disease. Paediatric European Network for Treatment of AIDS (PENTA).
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.


OBJECTIVE
To describe the relationships between HIV-1 RNA, age and CD4 cell count in untreated vertically infected children.


METHODS
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 log10 copies/ml. The median plasma HIV-1 RNA at enrollment was 4.61 log10 (range, 2.3-6.56 log10 copies/ml), significantly higher in children aged < or = 2 years (median, 5.23 log10 copies/ml) than in those aged > 2 years (4.51 log10 copies/ml; P < 0.0001). Mean HIV-1 RNA fell by 0.38 log10 copies/ml per year up to 2 years of age, by 0.21 log10 copies/ml per year from 2 to 4 years of age, and by 0.03 log10 copies/ml per year from 4 to 6 years of age reaching a nadir of 4.25 log10 copies/ml at 6 years. Mean log10 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 log10 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.
D000375:Aging; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D017354:Point Mutation; D011786:Quality Control; D012367:RNA, Viral / Q000097:blood*; D019562:Viral Load; D014766:Viremia; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D012367:RNA, Viral; D015215:Zidovudine