July 14, 2003
In this poster, Matheron and colleagues presented follow-up data from a study that was recently published which looked at the 48-week safety and efficacy of two combination regimens comparing the three nucleoside analogue regimen of AZT (zidovudine, Retrovir) + 3TC (lamivudine, Epivir) + abacavir (ABC, Ziagen) versus Combivir (AZT + 3TC) plus the protease inhibitor nelfinavir (NFV, Viracept). It should be stated that nelfinavir was given three times daily in this study, compared to the current twice-daily dosing currently given.
This poster presented longer-term follow-up (two years or greater) data on patients still remaining on these regimens. The study included a single follow-up visit to analyze several laboratory parameters and clinical side effects of the regimens. There were 192 subjects enrolled in the original study (CNAF3007), 92 of whom were enrolled in the current study (47 in the AZT/3TC/abacavir arm and 45 in the AZT/3TC/nelfinavir arm).
The patients were analyzed in two ways. First, an intent to treat (ITT) analysis was used, in which all patients who were randomized and who received treatment were included. In an ITT analysis, patients with missing data or who have changed their regimen are considered failures. The authors also included an ITT in which a switch in therapy was not considered a failure. Second, they performed an as treated (AT) analysis, which evaluates only those people receiving the randomized treatment who generally manage to stay on the assigned treatment for the duration of the study. Usually an ITT analysis is a more rigorous way of looking at the data than an AT analysis.
The treatment arms were fairly evenly matched with respect to gender (75 percent male in each arm), age, baseline and week 48 viral load (from the first study); however, the baseline and week 48 mean CD4 counts were over 100 cells higher in the nelfinavir arm. At the two-year follow-up visit, patients were more likely to have remained on the AZT/3TC/abacavir arm (70 percent) compared to the AZT/3TC/nelfinavir arm (33 percent), and 80 percent were more likely to remain on their original AZT/3TC/abacavir arm for two years compared to 53 percent on the nelfinavir arm.
The specific reasons or side effects explaining why more people discontinued the nelfinavir arm were not presented. In the nelfinavir arm 11 out of 30 patients switched to abacavir. The follow-up visit (time on the regimen) was almost one year longer on the AZT/3TC/abacavir arm. There was a small, but not significant further increase in CD4 count in both the ITT and AT analyses.
In an ITT analysis in which switching regimens equals failure, 55 percent of the AZT/3TC/abacavir arm versus 24 percent of the AZT/3TC/nelfinavir arm had an undetectable viral load (less than 50 copies/mL). If one looks at the AT analysis, 26/33 (79 percent) of the AZT/3TC/abacavir arm and 9/13 (69 percent) of the AZT/3TC/nelfinavir arm had an undetectable viral load, implying that for those who stayed on the nelfinavir regimen and had not failed or switched, the level of sustained response was almost the same as the abacavir arm. There was no difference in the glucose or triglyceride levels between arms. There was a minimal increase in total cholesterol in the nelfinavir arm compared to no increase in the abacavir arm. There was no difference between the treatment arms with respect to signs of lipodystrophy.
This study indicates that a regimen of AZT/3TC/abacavir is apparently better tolerated and more durable in terms of virologic response compared to a regimen of AZT/3TC/nelfinavir. AZT/3TC/abacavir is probably associated with better adherence to a twice-daily regimen and lower pill counts, and less gastrointestinal side effects, although this was not specifically stated in the poster. How an AZT/3TC/abacavir regimen would compare to an AZT/3TC/nelfinavir regimen, with nelfinavir given twice daily, or with the new formulation (two 625 mg tablets given twice daily), thereby reducing the doses and pill burden, is not known.
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