Immune Reconstitution and Viral Load Response In Antiretroviral Naive Vertically HIV-Infected Children Enrolled In The PENTA 5 Trial
D. M. GIBB*1‚2, N. KLEIN2, A. DE ROSSI3, I. GROSCH-WÖRNER4, A. NEWBERRY1, A. BABIKER1, and the PENTA Steering Committee. 1Med. Res. Council Clin. Trials Unit, London, UK; 2Inst. of Child Hlth., London, UK; 3AIDS Reference Ctr., Padova, Italy; and 4Charite-Virchow-Klinikum, Berlin, Germany
Methods: Twenty five antiretroviral naive vertically HIV infected children from 3 European centres (17 UK, 5 Italian, 2 German) enrolled in a clinical trial (PENTA 5) of 2 NRTI (2 of Abacavir, ZDV or 3TC) plus Nelfinavir (in all but 2 children who received 2 NRTI's alone) had HIV RNA viral load (VL, Amplicor Monitor, Roche), T cell subsets and memory and naive CD4 and CD8 phenotype measurements (using 3-colour flow cytometry) at baseline (x2) 2, 4 weeks, 4 weekly to week 24, and 8 weekly thereafter. Results: Median follow-up to date is 53 (12-81) weeks. 17 children were black African. At trial entry, CDC stage was C1 (n=2), B (n=14) A or N (n=9). Median (range) age was 5.4 (0.3-12.7) years; CD4 percent 14 (1-45)% with 58% of cells being CD45RA+CD4+ (naive); median baseline CD8% was 49 (29,67)% with 60% of cells being naive. Mean baseline VL was 5.28 (SD 0.6) log copies/ml and decreased by 2.99 (SD 0.8) log copies/ml at 24 weeks; the proportion of children with VL <400 copies/ml was 78% and 62% at 24 and 48 weeks respectively. CD4% increased from baseline by 9 (-1,15)% to week 24 and 13 (4,29)% to week 48. No early increase in percent CD45RO+CD4+ (memory) cells was observed; conversely the rise in CD45RA+CD4+ cells was rapid and 62 (36-100)% of reconstituted CD4+ cells were naive at 24 weeks and 75 (43-96)% at 48 weeks. CD8% decreased from baseline by 5% to week 48, with 66% being naive. In children followed for at least 20 weeks, younger age was inversely correlated with the increase in naïve cells (r=0.4, p=0.08), but the correlation with VL nadir was not significant (r=0.2, p=0.3). Conclusion: HAART resulted in a substantial increase in CD4+ cells, particularly in younger children. Greater thymic activity among children at all stages of HIV disease is suggested by the higher proportion of naive CD4+ than observed in adults. Follow-up of these children is continuing and studies analysing changes in the V-beta family repertoire are ongoing.
Key Words: HAART, Immune function, Paediatric
Conference on Retroviruses and Opportunistic Infections,