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Abstract
3TC +ABC maintains virological superiority over ZDV+3TC and ZDV+ABC beyond 5 years in children: the PENTA 5 trial
D.M. Gibb1, H. Green1, Y. Saidi2, D. Pillay3, A. Compagnucci2, L. Harper1, A.S. Walker1, G. Castelli-Gattinara4, M. della Negra5, J. Levy6, F. Candeias7, K. Butler8, C. Feiterna-Sperling9, U. Wintergerst10, C. Giaquinto11, on behalf of PENTA 5
1Medical Research Council Clinical Trials Unit, London, United Kingdom, 2INSERM SC10, Paris, France, 3University College London and Health Protection Agency, London, United Kingdom, 4Ospedale Bambin Gesù, Rome, Italy, 5Instituto de Infectologia 'Emilio Ribas', São Paolo, Brazil, 6Hôpital Saint Pierre, Brussels, Belgium, 7Hospital de Dona Estefania, Lisbon, Portugal, 8Our Lady's Hospital, Dublin, Ireland, 9Humboldt-Universität, Berlin, Germany, 10Universitäts-Kinderkliniken, Munich, Germany, 11Università di Padova, Padova, Italy
Background: PENTA 5 was a 48-week randomised controlled trial comparing 3 dual NRTI combinations with or without NFV as first ART therapy. We describe long-term response to 5 years.
Methods: 128 ART-naïve children were randomised to ZDV+3TC (n=36), ZDV+ABC (45) or 3TC +ABC (47). Asymptomatic children (n=55) were also randomised to NFV or placebo; all other children received open-label NFV. 1 child was lost to follow-up and 1 died before 2 weeks, leaving data on 126 children with follow-up. Analyses are intent-to-treat and adjusted for minor baseline imbalances and receipt of NFV/placebo.
Results: Median follow-up was 5.8 years (IQR 5.2-6.5). By 5 years, 17 (47%), 27 (61%) and 18 (39%) children had changed their randomised NRTIs in the ZDV+3TC , ZDV+ABC and 3TC +ABC arms respectively, but 18%, 48% and 50% of these changes were either early single drug substitutions for toxicity or switches in children with viral suppression (plasma HIV-1 RNA viral load (VL) <400 copies/ml; e.g. for simplification). Of 105 children with VL at year 5, 55%/32% ZDV+3TC , 50%/25% ZDV+ABC and 79%/63% 3TC +ABC had VL <400/<50 copies/ml respectively (p=0.03/p=0.003). Corresponding decreases in log10 VL were 2.5, 2.5 and 3.6 respectively (p=0.001). Mean increase in CD4% was 14%, 10% and 12% (p=0.2); height-for-age 0.24, 0.39 and 0.79 (p=0.02); weight-for-age 0.19, 0.18 and 0.81 (p=0.02). Reverse transcriptase resistance mutations differed between the arms: ZDV+3TC (41, 184, 210 and 215); ZDV+ABC (67, 215); 3TC +ABC (65, 74, 115, 184). Of the 24 children randomised to dual NRTI only, 0/7 ZDV+3TC , 3/11 ZDV+ABC and 4/6 3TC +ABC were still taking only 2 drugs at year 5 (0, 1, and 3 with VL <400 copies/ml).
Conclusions: Improved efficacy, in terms of VL suppression and growth changes, and lower rates of switching with detectable VL in the 3TC +ABC arm were sustained through to year 5.
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