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*1 started stavudine and substituted zidovudine at 12 weeks, 2 started abacavir and did not change (both prescribing errors) **2 started zidovudine and.

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Presentation on theme: "*1 started stavudine and substituted zidovudine at 12 weeks, 2 started abacavir and did not change (both prescribing errors) **2 started zidovudine and."— Presentation transcript:

1 *1 started stavudine and substituted zidovudine at 12 weeks, 2 started abacavir and did not change (both prescribing errors) **2 started zidovudine and did not change (1 prescribing error and 1 child changed regimen to match twin sibling) aincludes 1 not seen after randomisation Not randomised(n=154) Protocol exclusion criteria(n=151) WHO criteria for ART not met(n=59) on ART, VL>50 copies/ml(n=28) laboratory abnormality (n=26) unwilling to attend (n=20) acute TB treatment(n=5) HIV negative (n=4) <1 year, peri-natal ART(n=4) acute opportunistic infection (n=3) contra-indicated medication(n=2) Other reason(n=3) did not return(n=3) Screened (n=634) Randomised (n=480) Figure 1. Trial profile Stavudine (n=156) No exclusions (n=156) Allocation Analysis Follow-up Abacavir (n=165) 1 exclusion (n=164) subsequently found to be HIV uninfected Zidovudine (n=159) 1 exclusion(n=158) <3 years on induction TB treatment Given trial drugs(n=156) 1 withdrawn and not seen after enrolment Not known to have died, last seen before study end (n=11) 8 lost to follow-up a 3 withdrew consent Died before trial end (n=7) Given trial drugs(n=164) 2 not as randomised ** 1 lost to follow-up and not seen after enrolment Not known to have died, last seen before study end (n=6) 4 lost to follow-up a 2 withdrew consent Died before trial end (n=9) Given trial drugs(n=158) 3 not as randomised * Not known to have died, last seen before study end (n=8) 5 lost to follow-up 3 withdrew consent Died before trial end (n=3)

2 2a. 2b. Figure 2, Adverse Events 2a, primary endpoint (clinical grade 2+, lab grade 3 confirmed, lab grade 4 all) 2b, first grade 3/4 event 0.00 0.25 0.50 0.75 1.00 061218243036 Months from randomisation Proportion without endpoint StavudineZidovudineAbacavir ART experienced ART naïve Number at risk (events) 13060(66)44(16)38(6)30(3)10(0)2(1)abacavir 11250(60)37(11)32(5)22(3)10(3)2(1)zidovudine 12347(75)34(11)30(4)23(3)12(1)1(0)stavudine 3427(7)23(4)22(1)20(1)12(0)3 abacavir 4637(9)30(7)28(2)27(1)13(1)5(0)zidovudine 3329(4)25(3)23(2)21(1)9(0)2 stavudine ART naive ART experienced p=0.63 heterogeneity p=0.41 p=0.48 heterogeneity p=0.59

3 3a. 3b. Figure 3, Viral Suppression 3a, <400 copies/ml 3b, <100 copies/ml 128117111abacavir 108101102zidovudine 119115106stavudine 3432abacavir 45 zidovudine 32 stavudine ART naive ART experienced N 34 45 32 ART naive ART experienced ART naive P=0.51P=1.00 P=0.58 P=0.46 P=0.82P=0.33 P=0.61P=0.79 S: 67% Z vs S: +6.3% (-5.9,18.5) A vs S: +4.0% (-7.9,15.9) A vs Z: -2.3% (-14.3,9.6) S: 73% Z vs S: +1.9% (-10.1,13.8) A vs S: +3.9% (-7.6,15.5) A vs Z: +2.1% (-9.5,13.6) S: 85% Z vs S: -5.0% (-15.1,5.1) A vs S: -4.0% (-13.6,5.6) A vs Z: +1.0% (-9.5,11.5) S: 75% Z vs S: +1.0% (-10.6,12.6) A vs S: +6.5% (-4.4,17.4) A vs Z: +5.5% (-5.4,16.4) S: 97% Z vs S: -8.0% (-19.0,3.0) A vs S: +0.2% (-8.1,8.5) A vs Z: -+8.2% (-2.6,19.0) S: 94% Z vs S: +4.0% (-5.4,13.5) A vs S: +3.1% (-7.2,13.5) A vs Z: -0.9% (-8.3,6.5) S: 97% Z vs S: -1.3% (-9.8,7.2) A vs S: -+0.2% (-8.1,8.5) A vs Z: +1.5% (-6.8,9.8) S: 97% Z vs S: +3.1% (-2.9,9.2) A vs S: +0% (-8.5,8.5) A vs Z: -3.1% (-9.2,2.9)

4 4b. Figure 4, Resistance 4a, Major NRTI mutations in those >500 copies/ml at week 96 4b, Predicted drug susceptibility in those >500 copies/ml at week 96 4a. 0 20 40 60 80 100 Percentage with mutation (95% CI) 41L65R67N70E/r74V115F151M184V/I210W215F/Y219E/Q StavudineZidovudineAbacavir 0 20 40 60 80 100 Percentage with int/high resistance according to Stanford (95% CI) 3TCFTCABCDDIZDVD4TTDFEFVNVPETRRPV StavudineZidovudineAbacavir


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