July 11, 2002
There is a lot of interest in the concept of induction/maintenance as an antiviral therapy strategy. Early studies of the concept (ACTG 343 and Trilege) utilized a three-drug induction regimen and a two-drug maintenance regimen. The overall poor performance of the two-drug maintenance therapy arms underscored that a two-NRTI drug regimen is not potent enough (and doesn't have a high enough barrier to resistance). Many clinicians (including myself) often clinically utilize a four-drug induction regimen and then switch to a simpler three-drug regimen after a patient's viral load has reached the level of detection and the patient has demonstrated a high level of adherence. We do that even in the absence of good data about the long-term clinical utility of that strategy.
S. Kinoch and colleagues examined the strategy in the context of the Quest Study that utilized a four-drug regimen (amprenavir, abacavir, AZT, and 3TC) for the treatment of primary HIV infection. This analysis looked at the experiences of those patients whose physician (not protocol mandated) decided to simplify the regimen by stopping the amprenavir.
That strategy was allowed in two groups of patients. Group one had a viral level of less than 50 copies/ml (n = 69) and group two had documented viral levels less than or equal to 10 copies/ml (n = 57). Twenty-eight of the group one patients and 24 of the group two patients simplified their regimen. The authors then analyzed the virologic outcomes for both groups comparing those subjects in both groups who had simplified their regimen with those who continued the original four-drug regimen. The relative hazard for virologic failure over a 48-week observation was near one for both comparisons (p = 0.8) suggesting that the simplified three-drug maintenance regimen was as effective as the four-drug regimen. They also looked at CD8+ T-cell activation markers and found no difference between the simplified treatment arm and the continuation arms.
Though this study provides some modest reassurance that a three-drug maintenance regimen is effective at maintaining viral suppression, there are several caveats. First, this study involved patients who started treatment during primary infection and may not be generalizable to the setting of chronic HIV infection. Secondly, the clinical use of amprenavir as a PI is minimal (in the absence of ritonavir boosting and reduced doses) due to lack of potency and an awkward regimen (large number of large pills). The use of amprenavir as the fourth drug may lead to sub-optimal potency or adherence that makes it a poor comparative arm in an induction/maintenance study. Further studies on the induction/maintenance strategy are clearly needed.
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