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JMD 2006, Vol. 8, No. 4
Copyright © 2006 American Society for Investigative Pathology & Association for Molecular Pathology

Technical Advance

Sensitivity of the ViroSeq HIV-1 Genotyping System for Detection of the K103N Resistance Mutation in HIV-1 Subtypes A, C, and D

Jessica D. Church^*, Dana Jones^*, Tamara Flys^*, Donald Hoover, Natalia Marlowe, Shu Chen, Chanjuan Shi^*, James R. Eshleman^*, Laura A. Guay^*, J. Brooks Jackson^*, Newton Kumwenda, Taha E. Taha and Susan H. Eshleman^*

From the Department of Pathology, * The Johns Hopkins School of Medicine and the Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland; the Department of Statistics and Institute for Health, Health Care Policy and Aging Research, Rutgers University, Piscataway, New Jersey; Celera Diagnostics, Alameda, California

Abstract

The US Food and Drug Administration-cleared ViroSeq HIV-1 Genotyping System (ViroSeq) and other population sequencing-based human immunodeficiency virus type 1 (HIV-1) genotyping methods detect antiretroviral drug resistance mutations present in the major viral population of a test sample. These assays also detect some mutations in viral variants that are present as mixtures. We compared detection of the K103N nevirapine resistance mutation using ViroSeq and a sensitive, quantitative point mutation assay, LigAmp. The LigAmp assay measured the percentage of K103N-containing variants in the viral population (percentage of K103N). We analyzed 305 samples with HIV-1 subtypes A, C, and D collected from African women after nevirapine administration. ViroSeq detected K103N in 100% of samples with >20% K103N, 77.8% of samples with 10 to 20% K103N, 71.4% of samples with 5 to 10% K103N, and 16.9% of samples with 1 to 5% K103N. The sensitivity of ViroSeq for detection of K103N was similar for subtypes A, C, and D. These data indicate that the ViroSeq system reliably detects the K103N mutation at levels above 20% and frequently detects the mutation at lower levels. Further studies are needed to compare the sensitivity of different assays for detection of HIV-1 drug resistance mutations and to determine the clinical relevance of HIV-1 minority variants.