October 26, 2001
The TRIZAL study is the third of the abacavir switch studies to report data. Two other published studies have demonstrated that switching from a protease inhibitor (PI) to abacavir maintained virological control to the same degree as in persons with established viral suppression <50 copies/ml who continued protease inhibitor use while on first-line therapy. Patients on second-line therapy who had received AZT alone or as dual therapy before didn't do so well after switching, with about 30% experiencing viral rebound in the Swiss study. This contrasts with the two randomized efavirenz switch studies, where maintenance of virologic control was actually superior to protease inhibitor continuation. The advantage to abacavir switching relative to efavirenz replacement of protease inhibitor is that lipids such as cholesterol and triglycerides generally improve with abacavir but tend to stay the same with efavirenz.
The TRIZAL study randomized 209 French and British patients with viral loads <50 copies/ml and who were stable on first-line triple therapy (62% on PI, 19% on NNRTI, 17% on triple NRTI) to either remain on therapy or change to trizivir (AZT+3TC+ABC combined tablets). Patients were assessed at baseline and subsequent timepoints with fasting bloods and physicians were asked to assess the patients three times monthly for physical signs suggestive of lipodystrophy.
Virological control was similar at week 48, with 75% of abacavir and 69% of continuation patients (by intention to treat, 94% and 90% by as-treated) maintaining <50 copies/ml. The total cholesterol level fell in both groups, but by a significantly greater amount in the group that switched to trizivir. Median change in cholesterol was -0.44 mmol/l and -0.8 mmol/l. Nine percent of trizivir patients had an increase in cholesterol toxicity grade, whereas 40% had a decrease in grade. For continuation patients, 29% had a decrease in cholesterol grade and 10% and decrease in grade. Triglyceride results were similar to those for cholesterol, being lower by a median -0.17 mmol/l after the switch to trizivir but essentially unchanged (0.01 mmol/l higher) in the continuation arms. Triglyceride toxicity grades: 25% of trizivir patients saw an increase and 22% a decrease in grade compared with a 44% increase and a 4% decrease in the continuation arm. Data on intervention with lipid-lowering agents were not reported; however, the data suggest that the falls in lipids following the switch to trizivir were likely to reduce the need for future lipid-lowering therapy.
Regarding body shape assessments, non-significant differences between the groups were evident at baseline with fewer patients subsequently randomized to trizivir (40%) having at least one sign of lipodystrophy compared to 50% of patients subsequently randomized to remain on therapy. This difference, which occurred by chance, may make the interpretation of the on-therapy data difficult. Remarkably, both groups saw a reduction in the number of subjects with at least one lipodystrophy sign. This is surprising given that their lipodystrophy signs had developed while on first-line therapy. The improvements reported may therefore be observer-influenced; in which case the observers became accustomed over time to the mild physical signs of lipodystrophy and began to view them as "normal," whereas, at first sight, they had appeared "abnormal." No objective assessments of body shape were reported. The number of participants with at least one sign of lipodystrophy fell by 12% in the switch group and 8% in the continuation group. New signs of lipodystrophy without resolution were seen in 12% of trizivir and 20% of continuation patients (this difference was not significant), suggesting that lipodystrophy may still progress on the trizivir regimen. Resolution of one sign without any new signs of lipodystrophy appearing occurred in 63% of switch and 34% of continuation patients, this difference being statistically significant. The types of signs that resolved or reappeared were not reported. Breakdown of responses by treatments at baseline was not reported, so it is unclear if all responders were patients who had dropped their protease inhibitor.
The data support the idea of switching to trizivir in patients on first-line therapy with a protease inhibitor and perhaps with other drugs when lipids are elevated or when lipodystrophy is present. However, as the data show, while most people appear to benefit from this approach in terms of lipids or morphology, some patients see new symptoms appearing or lipid grades worsening. Thus, expectations of benefit should not be too high.
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