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ACTG5202
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Reported by Jules Levin
CROI 2010 Feb 16-19, SF
Data Safety Monitoring Board recommended unblinding of the ABC arm with patients having choice to switch off or remain on assigned NRTI regimen and remain in study, because as you can see on left panel there were more events regarding Time To Virologic Failure in the ABC/3TC arm. Late last time the data were published.
Unlike in the high viral load group there was no demonstrable difference in time to viral failure in the low baseline viral load group.
Eric Daar, the presenter, said "There were differences between ABC & TDF for the primary safety & tolerability endpoints. For safety events for the nukes there was no difference with ATV/r but a shorter time to safety events for ABC/3TC with EFV. Most of the safety events were in the category of general body complaints such as aches, pains, fever and fatigue or grade 3-4 cholesterol elevation. For the tolerability endpoint there was a shorter time to regimen modification with ABC/3TC than with TDF/FTC when combined with both ATV/r and EFV, much of the difference appears to be driven by hypersensitivity reactions listed below in the slide on the rightside panel. Notably HLA-B*5701 testing was not the standard of care when this study was enrolled."
Based on study potocol they could not declare equivalence but the differences between ABC/3TC and TDF/FTC was very small as you can see in slide (83.4 vs 85.3%) and 89.0 vs 89.8%).
Daar said "For the primary safety endpoint ATV/r vs EFV with TDF/FTC was not different but when used with ABC/3TC there was a shorter time to safety events with EFV as seen here in yellow most of which were related to the general body complaints and grade 3-4 cholesterol elevation similar to what was seen with the nuke comparison in the low viral load strata."
Daar said "For the primary tolerability endpoint there was no difference between the 3rd drugs when used with TDF/FTC but a shorter time to regimen modification when EFV was combined with ABC/3TC as seen here in the yellow line. The most common reasons for modification for EFV was viral failure, CNS symptoms, rash, allergic reaction. And for ATV/r it was non-compliance with meds, study visits or jaundice."
Daar said "there was no apparent difference in these events by study arm".
Daar said "It's clear that the emergence of resistance was significantly more common in those treated with EFV compared to ATV/r regardless of the nuke comparison and this was also true with a significantly higher frequency of nuke resistance within these groups".
Increase in CD4 was a secondary endpoint. The CD4 increases were similar for ATV/r vs EFV when combined with ABC/3TC. There was a significantly greater increase in CD4 when ATV/r was combined with TDF/FTC compared to EFV at 48 & 96 weeks.
Daar said "This is the As-Treated comparison between PI and NNRTI for change in lipids at 48 weeks. EFV compared to ATV/r was consistently associated with significantly greater increases in total cholesterol, LDL and HDL and this was true regardless of whether it was with ABC/3TC or TDF/FTC. There is a suggestion here that the magnitude of change was also higher with ABC/3TC than TDF/FTC. In fact in the similar analyses comparing the nukes in the low viral load stratum there was a significantly greater increase in the same cholesterol parameters with ABC/3TC compared to TDF/FTC with both the PI & NNRTI. In this case there is also significantly greater increase in triglycerides when ABC/3TC was combined with ATV/r. Notably there was no difference in total cholesterol or HDL ratio in any of these comparisons."
Daar said "In this last secondary analysis is the change in calculated creatinne clearance a 48 & 96 weeks. In this comparison there was no difference when either ATV/r or EFV was used with ABC/3TC. But a modest decline when ATV/r was used with TDF/FTC as opposed to what was seen when TDF/FTC was used with EFV. A similar relationship was seen in the low viral load stratum nuke comparison. It's noteworthy that the changes were modest and no more than 5% of individuals in any study arm that experienced greater than 25% decline in creatinine clearance from baseline through 96 weeks of followup."
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