Minimizing resistance consequences after virologic failure on initial combination therapy: A systematic overview
Objective: To identify optimal first-line therapies based on the rate of virologic success (VS) and the preservation of future treatment options in antiretroviral therapy (ART)-naive subjects.
Design: Systematic overview of genotypic resistance mutations from clinical trials of combination ART.
Methods: Various sources were searched for studies in ART-naïve subjects providing virologic response rates and genotypes from subjects with virologic failure. The International AIDS Society-USA genotypic resistance guidelines were used to calculate regimen resistance cost (RCreg) and number of active drug (AD) scores for each regimen and to rank the regimens.
Results: Intra- and interstudy comparisons showed higher VS rates for nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens (range: 51%Y76%) and boosted protease inhibitor (boosted PI) regimens (range: 55%Y79%). Boosted PI failures had the lowest RCreg (range: 0.12Y0.21) and the highest AD (range: 19.80Y20.18) scores. NNRTI failures had higher RCreg (range: 0.00Y1.22) and lower AD (range: 16.83Y21) scores.
Conclusions: NNRTI and boosted PI regimens provide the highest rates of VS in treatment-naive HIV-infected persons. Treatment option scores were higher in subjects who failed boosted PIY containing regimens versus NNRTI-containing regimens, however.