June 30, 1998
This study compared the triple combination of AZT/3TC/efavirenz with the double combo of AZT/3TC in naïve patients. Early in the study, it became clear from new research that AZT/3TC was not adequate, and patients who had started on the double combo changed nukes to ddI and d4T and added both efavirenz and indinavir. It was a double-blind, placebo-controlled study of 137 patients, and there were initially 3 efavirenz doses (200 mg or 400 mg or 600 mg). Mean HIV RNA 4.7 ± 0.5 log10 copies/mL, mean CD4 count 370 ± 194 cells/mm3. Using the optimistic (and widely used) as treated analysis (only looking at those still taking their treatment), 100% of those on efavirenz 600 mg (now the recommended dose) were below 400 copies at 24 weeks and 36 weeks. 80 to 95% of those who started at suboptimal doses were below 400 copies at 24 weeks and 36 weeks. Of those who started on AZT/3TC and intensified, 65 to 70% were below 400 at week 24 and it appeared to be dropping after that. Using the stricter intent to treat analysis, 80% of those in the three efavirenz containing arms were less than 400 copies. CD4 increases were between 100 and 150 cells at 36 weeks and still increasing. As with all efavirenz studies, some patients experienced sleepiness, insomnia, difficulty concentrating or euphoria, but in most cases it cleared up and was tolerable. This study complements the 006 study in showing that 2 nukes and efavirenz is an excellent "protease sparing" regimen in drug naïve patients, at least over 24 to 36 weeks. It is reassuring that during the dose ranging studies, people who got lower doses of efavirenz with potent nukes did not have early resistance.