Although the drug efavirenz (Sustiva) has been available in North America for several years, its manufacturer has only recently released detailed results about its effectiveness. According to data from Trial 006, efavirenz - when used together with AZT and 3TC - is as effective in reducing viral load and raising CD4+ cell counts as a combination of indinavir with AZT and 3TC. The people in this trial had never received a protease inhibitor, efavirenz or similar drugs. Over the 48 weeks of the trial, fewer subjects on efavirenz than subjects on indinavir dropped out.
Researchers recruited 450 subjects (14 per cent female, 86 per cent male) and randomly assigned them to one of three groups (or arms). Each group received one of the following combinations of drugs:
Drugs were taken at standard doses in the first two arms. In the group receiving efavirenz and indinavir, the dose of indinavir was increased to1,000 milligrams every eight hours. At the time subjects entered the study, they had an average
Subjects in the study were not supposed to have used 3TC, protease inhibitors or efavirenz, delavirdine or nevirapine. All subjects knew which combinations of drugs they were receiving.
By the end of the 48th week, the following proportion of subjects in each group had viral load levels below the 50-copy mark:
This difference in viral load between the efavirenz, AZT and 3TC group and the indinavir, AZT and 3TC group was statistically significant.
The researchers also examined the impact of the drugs on those subjects with relatively high viral loads: that is, on subjects whose viral loads were 100,000 copies or greater at the start of the study. The following proportion of subjects in each group had viral loads below the 50-copy mark by the end of the study:
This difference between the first two groups was statistically significant.
On average, subjects in all three groups experienced increased CD4+ cell counts ranging from 185 to 201 extra cells. There were no significant differences between the groups.
According to the researchers, the number of new AIDS-related infections was considered generally low. The number of subjects in each group who developed infections was as follows:
These differences in the number of infections between the groups was not statistically significant.
Certain side effects were significantly more common in subjects receiving triple therapy containing indinavir than in either efavirenz-containing group. These side effects included the following symptoms:
Subjects who receiving efavirenz and indinavir alone experienced more of the following side effects:
Two types of side effects were more common among subjects receiving efavirenz. The first was a rash that lasted for about two weeks. According to the doctors, in no subject was the rash "severe." The proportion of subjects with rash among the three groups was as follows:
The second type of side effect includes several symptoms that affects the central nervous system (CNS). The proportion of subjects with these symptoms among the three groups was as follows:
This difference in type of side effects on the central nervous system was startling and statistically significant. Symptoms included the following:
A. The combination of efavirenz and two nukes was more effective than indinavir and two nukes.
B. Efavirenz was as effective in people with a viral load of 100,000 copies or higher as it was in people with smaller viral loads.
C. Most subjects in this study had not previously received anti-HIV therapy. Results of triple therapy with efavirenz may, therefore, be different for people who have been exposed to these drugs.
D. It is possible that better results seen with efavirenz are due to the complicated compliance requirements associated with indinavir. Among these requirements are remembering to drink 1.5 litres of extra liquid each day and differentiating between snacks and meals, both of which may pose challenges for some people. As well, there is the issue of having to take indinavir every eight hours. In contrast, some people may prefer efavirenz's once-daily dosing.
E. Another point is that this study lasted for only one year. Different results may have appeared had the study continued for longer. Also, had a once- or twice- daily protease-inhibitor regimen been used instead of indinavir, different results may have emerged.
F. The final word on efavirenz is not in yet. A two-year study comparing triple therapy with efavirenz to another protease-inhibitor containing regimen is under way.
1. Staszewski S, Morales-Ramirez J, Tashima KT, Rachlis A, et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. New England Journal of Medicine 1999;341:1865-1873.
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