Background: Resistance testing is increasingly accepted as a tool in guiding the selection of human immunodeficiency virus type 1 (HIV-1) antiretroviral therapy in HIV-1 infected individuals who fail their current regimen. Objectives: To descriptively compare the correlation between virologic treatment response and results using three genotypic HIV-1 drug resistance interpretation systems: the VERSANT(R) HIV-1 Resistance Assay (LiPA) system and two sequence-based interpretation systems. Study design: Specimens from 213 HIV-1-infected subjects, either starting (n = 104) or switching to (n = 109) a regimen of three or four antiretroviral drugs, were collected retrospectively at baseline and after 3 months of uninterrupted therapy. The correlation between viral load change and the number of predicted active drugs in the treatment regimen was assessed. An interpretation algorithm was recently developed to process VERSANT(R) HIV-1 Resistance Assay (LiPA) data. The number of active drugs predicted using this algorithm was rank correlated with the viral load change over a 3-month treatment period. For comparison, a similar calculation was made using two sequence-based algorithms (REGA version 5.5 and VGI GuideLines(TM) Rules 4.0), both applied on the same sequences. Results: Statistically significant (p < 0.05) correlation coefficients for each of the three HIV-1 drug resistance interpretation systems were observed in the treatment-experienced subjects on a 3-drug regimen (-0.39, -0.38, and -0.42, respectively) as well as on a 4-drug regimen (-0.33, -0.31, and -0.37, respectively). However, no significant correlation was observed in treatment-naive subjects, probably due to the very low frequency of drug resistance in these subjects. Conclusion: All three genotypic drug resistance interpretation systems (LiPA version 1, REGA version 5.5, and VGI GuideLines(TM) Rules 4.0) were statistically significantly correlated with virologic therapy response as measured by viral load testing. (C) 2004 Elsevier B.V. All rights reserved.