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. 2004 Aug;42(8):3670-4.
doi: 10.1128/JCM.42.8.3670-3674.2004.

Comparison of oligonucleotide ligation assay and consensus sequencing for detection of drug-resistant mutants of human immunodeficiency virus type 1 in peripheral blood mononuclear cells and plasma

Giovanina M Ellis  1 , Madhumita Mahalanabis, Ingrid A Beck, Gregory Pepper, Amy Wright, Shannon Hamilton, Sarah Holte, Willscott E Naugler, Diane M Pawluk, Chung-Chen Li, Lisa M Frenkel
Affiliations

Comparison of oligonucleotide ligation assay and consensus sequencing for detection of drug-resistant mutants of human immunodeficiency virus type 1 in peripheral blood mononuclear cells and plasma

Giovanina M Ellis et al. J Clin Microbiol. 2004 Aug.

Abstract

Drug-resistant mutants of human immunodeficiency virus type 1 (HIV-1) recede below the limit of detection of most assays applied to plasma when selective pressure is altered due to changes in antiretroviral treatment (ART). Viral variants with different mutations are selected by the new ART when replication is not suppressed or wild-type variants with greater replication fitness outgrow mutants following the cessation of ART. Mutants selected by past ART appear to persist in reservoirs even when not detected in the plasma, and when conferring cross-resistance they can compromise the efficacy of novel ART. Oligonucleotide ligation assay (OLA) of virus in plasma and peripheral blood mononuclear cells (PBMC) was compared to consensus sequence dideoxynucleotide chain terminator sequencing for detection of 91 drug resistance mutations that had receded below the limit of detection by sequencing of plasma. OLA of plasma virus detected 27.5% (95% confidence interval [CI], 19 to 39%) of mutant genotypes; consensus sequencing of the PBMC amplicon from the same specimen detected 23.1% (95% CI, 14 to 34%); and OLA of PBMC detected 53.8% (95% CI, 44 to 64%). These data suggest that concentrations of drug-resistant mutants were greater in PBMC than in plasma after changes in ART and indicate that the OLA was more sensitive than consensus sequencing in detecting low levels of select drug-resistant mutants.

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References

    1. Alexander, C. S., W. Dong, K. Chan, N. Jahnke, M. V. O'Shaughnessy, T. Mo, M. A. Piaseczny, J. S. Montaner, and P. R. Harrigan. 2001. HIV protease and reverse transcriptase variation and therapy outcome in antiretroviral-naive individuals from a large North American cohort. AIDS 15:601-607. - PubMed
    1. Balotta, C., A. Berlusconi, A. Pan, M. Violin, C. Riva, M. C. Colombo, A. Gori, L. Papagno, S. Corvasce, R. Mazzucchelli, G. Facchi, R. Velleca, G. Saporetti, M. Galli, S. Rusconi, and M. Moroni. 2000. Prevalence of transmitted nucleoside analogue-resistant HIV-1 strains and pre-existing mutations in pol reverse transcriptase and protease region: outcome after treatment in recently infected individuals. Antivir. Ther. 5:7-14. - PubMed
    1. Bardeguez, A. D., D. E. Shapiro, L. M. Mofenson, R. Coombs, L. M. Frenkel, M. G. Fowler, S. Huang, R. S. Sperling, B. Cunningham, J. Gandia, R. Maupin, C. D. Zorrilla, T. Jones, M. J. O'Sullivan, and the Pediatric AIDS Clinical Trials Group 288 Protocol Team. 2003. Effect of cessation of zidovudine prophylaxis to reduce vertical transmission on maternal HIV disease progression and survival. J. Acquir. Immun. Defic. Syndr. Hum. Retrovirol. 32:170-181. - PubMed
    1. Baxter, J. D., D. L. Mayers, D. N. Wentworth, J. D. Neaton, M. L. Hoover, M. A. Winters, S. B. Mannheimer, M. A. Thompson, D. I. Abrams, B. J. Brizz, J. P. Ioannidis, and T. C. Merigan. 2000. A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS. AIDS 14:F83-F93. - PubMed
    1. Beck, I. A., M. Mahalanabis, G. Pepper, A. Wright, S. Hamilton, E. Langston, and L. M. Frenkel. 2002. Rapid and sensitive oligonucleotide ligation assay for detection of mutations in human immunodeficiency virus type 1 associated with high-level resistance to protease inhibitors. J. Clin. Microbiol. 40:1413-1419. - PMC - PubMed

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