About The Study
The study was to compare a four-drug combination (AZT + 3TC + abacavir + amprenavir) to a three-drug combination (AZT + 3TC + nelfinavir). The primary objectives of the study were to demonstrate that the long-term durability of HIV suppression of the four-drug combination is superior to that of the three-drug combination, and to compare the long-term safety and tolerability of treatment of the two combinations.
Study Approach
This was an international, randomized, open-label study, where volunteers were assigned to two treatment groups. One group received amprenavir (200 mg twice a day) plus abacavir (300 mg twice a day) plus CombivirTM (150mg of 3TC/300mg of AZT twice a day). The other group received nelfinavir (750 mg three times a day) plus Combivir (150mg of 3TC/300mg of AZT twice a day).
A change of protease inhibitors and replacement of AZT by d4T was allowed for intolerance. Treatment failure was defined as failure to achieve a viral load equal to or below 120 copies/ml by week 24 or confirmed viral rebound above 120 copies/ml.
Study population
Three hundred and two antiretroviral naïve volunteers with viral load levels of at least 5,000 copies/ml and CD4 counts levels of at least 50 cells/mm3 entered the study, beginning March 1998. In the three-drug arm, the median values of viral load and CD4 counts at study entry were 36,308 copies/ml and 330, respectively. The values in the four-drug arm were 43,652 copies/mL and 356, respectively.
Results
The primary analysis found that time to viral load above120 copies/ml occured earlier in the four-drug arm owing to a greater number of adverse events and withdrawals. In participants reaching a viral load below 120 copies/ml, there was no difference in duration of viral suppression or time to virologic failure. An analysis of the participants remaining on treatment showed that 70 percent on the three-drug arm had a viral load below 120 copies/ml compared with 87 percent on the four-drug arm. The proportion of participants with a viral load below 40 copies/ml was 66 percent and 77 percent on the three- and four-drug arms, respectively. Median CD4 increase from study entry was 188 cells/mm3 in the three-drug arm and 185 cells in the four-drug arm. Median change in cholesterol AUCs was 28.3 and 14.4 mg/dl.
Conclusions
For those remaining on therapy, Combivir-based quadruple therapy achieved a greater proportion of participants with viral suppression, but therapy was complicated by more adverse events and withdrawals. Increase in cholesterol was significantly less with quadruple therapy.
Note: These results were taken from an abstract presented at the XIIIth International AIDS Conference in Durban, South Africa, July 9-14, 2000.