Fifth International Congress Drug Therapy in HIV Infection 22-26 October, 2000 Glasgow, UK

A RANDOMISED TRIAL EVALUATING THREE NRTI REGIMENS WITH AND WITHOUT NELFINAVIR IN HIV-INFECTED CHILDREN: 48-WEEK FOLLOW-UP FROM THE PENTA 5 TRIAL

D.M. Gibb for the PENTA 5 Executive and the PENTA Steering Committees
MRC HIV Clinical Trials Unit, 222 Euston Road, London, UK

Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL6.8
AIDS 2000, Oct 22-26;14(Suppl. 4);S8

PURPOSE OF STUDY: The PENTA 5 trial compared the efficacy and toxicity of 3TC+ZDV, ZDV+abacavir (ABC) and 3TC+ABC in antiretroviral therapy naïve HIV-infected children, if the clinician was uncertain whether to prescribe a PI, children were also randomised to receive NFV or NFV placebo (NFVp) in a blinded multifactorial design (part A); if they were certain a PI was required, children received open-label NFV (part B).

METHODS: 128 children were randomised from seven European countries and one centre in Brazil. Of these, 73 received open label nelfinavir (Part B) and 55 were randomised to nelfinavir or placebo (Part A). The primary endpoint for the NRTI comparisons was change in viral load, whereas for the NFV/ NFVp comparison, it was toxicity. Efficacy analyses were on an intent-totreat basis; toxicity analyses were on-treatment plus 30 days. We report preliminary 48-week data from this trial.

RESULTS: One child was lost to follow-up and one died of sepsis by 48 weeks. VL results are available on 119 children at 48 weeks. Median age was 5.2 year; median CD4% was higher in children in part A than in part B (25 versus 19%); mean HIV-1 RNA viral load (VL) was lower (4.6 versus 5.3 log₁₀ copies/ml). Eleven (8.6%) children had AIDS at baseline. In an ITT analysis at 48 weeks, VL was < 400 copies/ml in 43%, 63% and 70% of the 3TC+ZDV, ZDV+ABC and 3TC+ABC groups respectively (P = 0.05, global test) and < 50 copies/ml in 26%, 42%, and 49% (P = 0.11). Mean VL decreased from baseline by 1.69, 2.10 and 2.40 log₁₀ copies/ml in the three groups respectively after adjusting for baseline age, VL, CD4% and NFV (P = 0.03). Median CD4% increased by 9%, 9%, and 10% at 48 weeks (P = 0.74). One child had an ABC hypersensitivity reaction after 2 weeks on drug. Over a median of 50 weeks, 7, 11 and 4 children in the 3TC+ZDV, ZDV+ABC and 3TC+ABC groups respectively stopped or modified at least one drug because of toxicity, most frequently neutropenia or vomiting. 27/35 (77%) of children starting NFV/NFVp powder switched to tablets, which were well tolerated. In part A, 8 children (7/28 children on NFV, 1/25 on NFVp) experienced adverse events leading to modification of one or more drugs. Five GI events on NFV led to NFV modification (four) or discontinuation (one), compared with one modification on NFVp. As a secondary endpoint in part A, mean change in VL from baseline to week 24 was –1.77 and –2.31 log₁₀ copies/ml (P = 0.04) and from baseline to week 48 was –2.04 and –2.04 log₁₀ copies/ml (P = 0.99) in the NFV and NFVp arms respectively, adjusting for baseline age, VL CD4% and NRTI use. The proportion of children still on NFV and NFVp as randomised was 96% and 92% at 24 weeks and 93% and 79% at 48 weeks respectively.

CONCLUSIONS: The ABC-containing arms were well generally tolerated and resulted in the greatest reduction in VL. There were no serious concerns about NFV toxicity.

Presenting author: D.M. Gibb

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2000-10-22
PL6-8

Originally published in AIDS Volume 14, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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