October 25, 1999
These two studies were done to further evaluate the flexibility of combinations based on the use of the nonnucleoside efavirenz, also called Sustiva. The original study used AZT plus 3TC -- here the investigators studied Sustiva in combination with either d4T plus 3TC, as well as d4T with ddI. Both studies enrolled just over 60 people. The d4T/3TC study presented data out to 48 weeks, whereas the d4T/ddI study had data out to 24 weeks.
The results showed continued success with Sustiva-based combinations. The d4T/3TC combination showed that, at week 48, only one person had a viral load over 400 copies, and four were between 50 and 400 copies. Overall, 90% were below 50 copies at week 48 using an "on treatment" analysis, and 80% were below 50 copies using an "intent to treat" analysis. In the subset of people who had a viral load over 100,000 when starting the study, the results of suppression to below 50 copies was the same. There were three people (<5%) who discontinued due to adverse events -- two of the three events were linked to the expected side effects seen with Sustiva, while one person had an increase in liver function tests. There was an increase of about 190 CD4 cells by the end of 48 weeks.
The combination of d4T and ddI had similar results, although there were a few additional participants who were not below 50 copies by week 24 -- 81% on treatment were below 50 copies at week 24, while 67% were below 50 copies using the intent to treat analysis. Five people came off this combination due to adverse events -- with four of them stopping due to some degree of peripheral neuropathy, most of them judged as mild or moderate when they stopped. The degree of viral suppression for those who had a baseline viral load above 100,000 was the same as for those below 100,000, similar to what has been seen in other studies of nucleosides with efavirenz.
Overall, these results confirm what has been reported in the large DuPont study 006, demonstrating that the combination of two nucleosides and Sustiva can be very successful in terms of the likelihood of viral suppression. The choice of which two nucleosides can be used with efavirenz appears to be flexible, and the choice might be decided on factors other than expected differences in viral suppression.