Minimizing resistance consequences after virologic failure on initial combination therapy: A systematic overview
Bartlett, J. A., Buda, J., Von Scheele, B., Mauskopf, J., Davis, E. A., Elston, R., ... Lanier, E. R. (2006). Minimizing resistance consequences after virologic failure on initial combination therapy: A systematic overview. Journal of Acquired Immune Deficiency Syndromes, 41(3), 323-331.
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.