Apr, 1998

Plasma viral load and genotypic resistance patterns in children adding lamivudine to current reverse transcriptase inhibitor therapy (PENTA 4 Trial)


Authors:  Kaye S, Loveday C, Gibb DM., Newberry A.

Published in: 4th International Congress, November 8ht-12th 1998, Glasgow.  P_305


Apr, 1998

A randomized double-blind trial of the addition of lamivudine or matching placebo to current nucleoside analogue reverse transcriptase inhibitor therapy in HIV-infected children: the PENTA-4 trial


Authors: Aboulker JP, Babiker A, Carrière I, et al.

Published in: AIDS.1998;12(14):F151-F160

Objective To evaluate the toxicity, tolerability and effect on laboratory markers of adding lamivudine (3TC) to nucleoside analogue reverse transcriptase inhibitors (NRTI) in children with HIV-1 infection.

Methods HIV-1-infected children on stable NRTI therapy were randomized to receive 3TC syrup or tablets (4 mg/kg twice daily) or matching placebo in addition to existing therapy. Endpoints were serious adverse events, and changes in CD4 cell count and plasma HIV-1 RNA. Analyses were on an intention-to-treat basis.

Results A total of 162 (81 on 3TC, 81 on placebo) children [median age, 6.5 years; interquartile range (IQR), 4.1-10.1 years] were included. At randomization, 52 were receiving zidovudine (ZDV), 39 didanosine (ddl), 54 ZDV-ddl and 17 ZDV-zalcitabine (ddC); 32 (20%) had AIDS; median CD4 cell count was 328 x 10(6)/I (IQR, 127-696 x 10(6)/l), and median HIV-1 RNA was 4.9 log10 copies/ml (IQR, 4.3-5.4 log10 copies/ml). Median follow-up was 40 weeks (IQR, 29-49 weeks) and 76% of follow-up was on blinded therapy for both 3TC and placebo groups. There were 11 serious adverse events in the blinded phase [two clinical (both placebo) and nine laboratory (five 3TC, four placebo)], five (two 3TC, three placebo) resulting in stopping trial drug. At 24 weeks, the CD4 cell count was greater in the 3TC group by a median of 47 x 10(6)/l and HIV-1 RNA was lower by 0.30 log10 copies/ml (P = 0.03 and 0.002, respectively, versus the placebo group). The difference in reduction in HIV-1 RNA up to 24 weeks, as measured by area under the curve minus baseline, between 3TC and placebo groups was 0.38 log10 copies/ml (95% confidence interval, 0.12-0.65) greater in children taking ZDV-containing regimens at baseline, compared with those on ddl monotherapy (P = 0.005), after adjusting for other factors at baseline. Thirteen children developed new AIDS events (six on 3TC, four on placebo) of whom three died (all placebo).

Conclusions The addition of 3TC to current NRTI therapy in children was safe and well-tolerated. There was evidence that treatment changes in HIV-1 RNA viral load were greater in children taking regimens that included ZDV.


Mar, 1998

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)


Authors: Paediatric European Network for Treatment of AIDS (PENTA)

Published in: AIDS. 1998;12(4):F1-8

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 countwas 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.


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