Virologic Success and Resistance in Triple-Drug Regimens
Virologic Success and Resistance in Triple-Drug Regimens
Triple-drug regimens incorporating boosted PIs are associated with higher virologic success rates and less resistance than are other triple-drug regimens.
John A. Bartlett's review of 23 triple-drug studies became an instant classic in 2001 and was considered an important summary of the status quo of antiretroviral therapy at the time (ACC Nov 1 2001). Now, Bartlett and colleagues have updated these findings with studies published or presented through February 2004. For this analysis, they considered all studies in which subjects had no or minimal treatment experience and had at least 48 weeks of follow-up. Studies without genotypic information were excluded, as were nonrandomized case series, studies of acute HIV infection, and salvage therapy trials. Of the 176 studies identified, only 15 fulfilled all inclusion criteria. These studies had 30 trial arms, evaluating 18 different regimens.
Overall, virologic success rates (defined as the proportion of patients with viral loads <50 copies/mL at 48 weeks) were higher in this review than in the one published in 2001. Regimens containing boosted PIs or NNRTIs were associated with the highest rates of virologic success (range, 51%79%), compared with triple-NRTI therapies and regimens containing unboosted PIs (range, 40%62%). Failure of NNRTI-based regimens was associated with a higher resistance cost (i.e., fewer active drugs in genotypic testing) than was failure of boosted-PI regimens.
These results support current treatment recommendations and are consistent with the results of smaller studies: Boosted PIs are associated with a significant delay in development of resistance, and resistance is often limited to the non-PI components of the regimen. The explanation for this observation is probably multifactorial: Drug potency, sanctuary penetration, and high genetic barriers to resistance may all play a role.
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Triple-drug regimens incorporating boosted PIs are associated with higher virologic success rates and less resistance than are other triple-drug regimens.
John A. Bartlett's review of 23 triple-drug studies became an instant classic in 2001 and was considered an important summary of the status quo of antiretroviral therapy at the time (ACC Nov 1 2001). Now, Bartlett and colleagues have updated these findings with studies published or presented through February 2004. For this analysis, they considered all studies in which subjects had no or minimal treatment experience and had at least 48 weeks of follow-up. Studies without genotypic information were excluded, as were nonrandomized case series, studies of acute HIV infection, and salvage therapy trials. Of the 176 studies identified, only 15 fulfilled all inclusion criteria. These studies had 30 trial arms, evaluating 18 different regimens.
Overall, virologic success rates (defined as the proportion of patients with viral loads <50 copies/mL at 48 weeks) were higher in this review than in the one published in 2001. Regimens containing boosted PIs or NNRTIs were associated with the highest rates of virologic success (range, 51%79%), compared with triple-NRTI therapies and regimens containing unboosted PIs (range, 40%62%). Failure of NNRTI-based regimens was associated with a higher resistance cost (i.e., fewer active drugs in genotypic testing) than was failure of boosted-PI regimens.
Comment
These results support current treatment recommendations and are consistent with the results of smaller studies: Boosted PIs are associated with a significant delay in development of resistance, and resistance is often limited to the non-PI components of the regimen. The explanation for this observation is probably multifactorial: Drug potency, sanctuary penetration, and high genetic barriers to resistance may all play a role.
Source
Bartlett JA et al. Minimizing resistance consequences after virologic failure on initial combination therapy: A systematic overview. J Acquir Immune Defic Syndr 2006 Mar; 41:323-31.
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