Late Breaker No. LB16: Phase III, Multicenter, Randomized, Open-Label Study to Compare the Antiretroviral Activity and Tolerability of Efavirenz (EFV) + Indinavir (IDV), versus EFV + Zidovudine (ZDV) + Lamuvidine (3TC), versus IDV + ZDV + 3TC at 48 Weeks (Study DMP 266-006)

These data comprise followup on the 24 week and 36 week data from this study, presented respectively at the AIDS Conference in Geneva and at ICAAC in San Diego, and seem to confirm the durability of plasma antiviral response to multidrug therapy with EFV. This study enrolled 450 participants who were PI, NNRTI and 3TC treatment naïve, and who had baseline CD4 of 354 + 202 cells/mm³, and RNA PCR of 4.77 + 0.57 log copies/ml. Results at 48 weeks were reported in several ways, the observed data (OBS), and then the intent-to-treat analysis (ITT) which can further be reported two ways, by counting the last observation on study and carrying it forward (LOCF) and then counting someone who has not completed therapy-as-intended as a failure (NC=F). These last two methods are conservative ways of counting the events on study.

Those who reached PCR < 400 copies/ml
	OBS	LOCF	NC=F
EFV/ZDV/3TC	98%	86%	71%
EFV/IDV	83%	66%	53%
IDV/ZDV/3TC	86%	61%	48%

Statistically, there is a difference (p<0.05) between EFV/ZDV/3TC over IDV/ZDV/3TC, in all comparisons. The data have been criticized in that the IDV/ZDV/3TC group experienced much greater dropout (due to treatment side effects) making this group look worse in its achievement of viral load below 500 than the EFV/ZDV/3TC group. A 48% response rate (NC=F) is also lower than what has been reported in other studies with indinavir. But, raising the bar further to compare these three treatment groups in their ability to suppress viral load below 50 copies/ml:

	OBS	LOCF	NC=F
EFV/ZDV/3TC	90%	68%	65%
EFV/IDV	74%	55%	47%
IDV/ZDV/3TC	79%	50%	44%

Again, there was statistical superiority of the first group over thae last group (p<0.05).

Further analysis of a subgroup of study participants who exhibited viral burdens in excess of 100,000 copies/ml at baseline continued to show superiority of the ZDV/3TC/EFV arm, reassuring the potency of this regimen even in patients with much higher risk of disease progression. Adverse events were common in the EFZ arms of the study but were of low grade (I or II) in severity. Hallucinations or somnolence was observed in half of those on the ZDV/3TC/EFV arm, though these resolved within a two week time frame, and rash was seen in about 30% of EFV treated individuals.