Impact of Minority Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations on Resistance Genotype After Virologic Failure

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2012 Dec 25

PMID 23264671

Citations 27

Authors

Jonathan Z Li

Roger Paredes

Heather J Ribaudo

Michael J Kozal

Evguenia S Svarovskaia

Jeffrey A Johnson

Anna Maria Geretti

Karin J Metzner

Martin R Jakobsen

Katherine Huppler Hullsiek

Lars Ostergaard

Michael D Miller

Daniel R Kuritzkes

Affiliations

Soon will be listed here.

Abstract

Drug-resistant human immunodeficiency virus type 1 (HIV-1) minority variants increase the risk of virologic failure for first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. We performed a pooled analysis to evaluate the relationship between NNRTI-resistant minority variants and the likelihood and types of resistance mutations detected at virologic failure. In multivariable logistic regression analysis, higher NNRTI minority variant copy numbers, non-white race, and nevirapine use were associated with a higher risk of NNRTI resistance at virologic failure. Among participants on efavirenz, K103N was the most frequently observed resistance mutation at virologic failure regardless of the baseline minority variant. However, the presence of baseline Y181C minority variant was associated with a higher probability of Y181C detection after virologic failure. NNRTI regimen choice and preexisting NNRTI-resistant minority variants were both associated with the probability and type of resistance mutations detected after virologic failure.

Citing Articles

Impact of Low-Frequency Human Immunodeficiency Virus Type 1 Drug Resistance Mutations on Antiretroviral Therapy Outcomes.

Burdorf R, Zhou S, Amon C, Long N, Hill C, Adams L J Infect Dis. 2024; 230(1):86-94.

PMID: 39052733 PMC: 11272071. DOI: 10.1093/infdis/jiae131.

Towards Next-Generation Sequencing for HIV-1 Drug Resistance Testing in a Clinical Setting.

Teo C, Norhisham N, Lee O, Png S, Chai C, Yan G Viruses. 2022; 14(10).

PMID: 36298763 PMC: 9608942. DOI: 10.3390/v14102208.

HIV-1 Drug Resistance Assay Using Ion Torrent Next Generation Sequencing and On-Instrument End-to-End Analysis Software.

Pyne M, Simmon K, Mallory M, Hymas W, Stevenson J, Barker A J Clin Microbiol. 2022; 60(7):e0025322.

PMID: 35699434 PMC: 9297824. DOI: 10.1128/jcm.00253-22.

Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase.

Siedner M, Moorhouse M, Simmons B, de Oliveira T, Lessells R, Giandhari J Nat Commun. 2020; 11(1):5922.

PMID: 33262331 PMC: 7708638. DOI: 10.1038/s41467-020-19801-x.

Multi-Laboratory Comparison of Next-Generation to Sanger-Based Sequencing for HIV-1 Drug Resistance Genotyping.

Parkin N, Avila-Rios S, Bibby D, Brumme C, Eshleman S, Harrigan P Viruses. 2020; 12(7).

PMID: 32605062 PMC: 7411816. DOI: 10.3390/v12070694.

References

Tsibris A, Korber B, Arnaout R, Russ C, Lo C, Leitner T . Quantitative deep sequencing reveals dynamic HIV-1 escape and large population shifts during CCR5 antagonist therapy in vivo. PLoS One. 2009; 4(5):e5683. PMC: 2682648. DOI: 10.1371/journal.pone.0005683. View

Church J, Jones D, Flys T, Hoover D, Marlowe N, Chen S . Sensitivity of the ViroSeq HIV-1 genotyping system for detection of the K103N resistance mutation in HIV-1 subtypes A, C, and D. J Mol Diagn. 2006; 8(4):430-2. PMC: 1867617. DOI: 10.2353/jmoldx.2006.050148. View

Larder B, Kohli A, Kellam P, Kemp S, KRONICK M, Henfrey R . Quantitative detection of HIV-1 drug resistance mutations by automated DNA sequencing. Nature. 1993; 365(6447):671-3. DOI: 10.1038/365671a0. View

Ribaudo H, Haas D, Tierney C, Kim R, Wilkinson G, Gulick R . Pharmacogenetics of plasma efavirenz exposure after treatment discontinuation: an Adult AIDS Clinical Trials Group Study. Clin Infect Dis. 2006; 42(3):401-7. DOI: 10.1086/499364. View

Paredes R, Lalama C, Ribaudo H, Schackman B, Shikuma C, Giguel F . Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. J Infect Dis. 2010; 201(5):662-71. PMC: 2825289. DOI: 10.1086/650543. View

Ngo-Giang-Huong N, Jourdain G, Amzal B, Sang-A-Gad P, Lertkoonalak R, Eiamsirikit N . Resistance patterns selected by nevirapine vs. efavirenz in HIV-infected patients failing first-line antiretroviral treatment: a bayesian analysis. PLoS One. 2011; 6(11):e27427. PMC: 3223170. DOI: 10.1371/journal.pone.0027427. View

Halvas E, Wiegand A, Boltz V, Kearney M, Nissley D, Wantman M . Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment- experienced patients. J Infect Dis. 2010; 201(5):672-80. PMC: 2835354. DOI: 10.1086/650542. View

Weintrob A, Grandits G, Agan B, Ganesan A, Landrum M, Crum-Cianflone N . Virologic response differences between African Americans and European Americans initiating highly active antiretroviral therapy with equal access to care. J Acquir Immune Defic Syndr. 2009; 52(5):574-80. DOI: 10.1097/QAI.0b013e3181b98537. View

Johnson J, Li J, Wei X, Lipscomb J, Irlbeck D, Craig C . Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naïve populations and associate with reduced treatment efficacy. PLoS Med. 2008; 5(7):e158. PMC: 2488194. DOI: 10.1371/journal.pmed.0050158. View

10.

Codoner F, Pou C, Thielen A, Garcia F, Delgado R, Dalmau D . Dynamic escape of pre-existing raltegravir-resistant HIV-1 from raltegravir selection pressure. Antiviral Res. 2010; 88(3):281-6. DOI: 10.1016/j.antiviral.2010.09.016. View

11.

Metzner K, Giulieri S, Knoepfel S, Rauch P, Burgisser P, Yerly S . Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and -adherent patients. Clin Infect Dis. 2008; 48(2):239-47. DOI: 10.1086/595703. View

12.

Goodman D, Zhou Y, Margot N, McColl D, Zhong L, Borroto-Esoda K . Low level of the K103N HIV-1 above a threshold is associated with virological failure in treatment-naive individuals undergoing efavirenz-containing therapy. AIDS. 2010; 25(3):325-33. DOI: 10.1097/QAD.0b013e3283427dcb. View

13.

Hanna G, Johnson V, Kuritzkes D, Richman D, Brown A, Savara A . Patterns of resistance mutations selected by treatment of human immunodeficiency virus type 1 infection with zidovudine, didanosine, and nevirapine. J Infect Dis. 2000; 181(3):904-11. DOI: 10.1086/315329. View

14.

Liu J, Miller M, Danovich R, Vandergrift N, Cai F, Hicks C . Analysis of low-frequency mutations associated with drug resistance to raltegravir before antiretroviral treatment. Antimicrob Agents Chemother. 2010; 55(3):1114-9. PMC: 3067114. DOI: 10.1128/AAC.01492-10. View

15.

Geretti A, Fox Z, Booth C, Smith C, Phillips A, Johnson M . Low-frequency K103N strengthens the impact of transmitted drug resistance on virologic responses to first-line efavirenz or nevirapine-based highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2009; 52(5):569-73. DOI: 10.1097/QAI.0b013e3181ba11e8. View

16.

Kuritzkes D, Lalama C, Ribaudo H, Marcial M, Meyer 3rd W, Shikuma C . Preexisting resistance to nonnucleoside reverse-transcriptase inhibitors predicts virologic failure of an efavirenz-based regimen in treatment-naive HIV-1-infected subjects. J Infect Dis. 2008; 197(6):867-70. DOI: 10.1086/528802. View

17.

Li J, Paredes R, Ribaudo H, Svarovskaia E, Metzner K, Kozal M . Low-frequency HIV-1 drug resistance mutations and risk of NNRTI-based antiretroviral treatment failure: a systematic review and pooled analysis. JAMA. 2011; 305(13):1327-35. PMC: 3325645. DOI: 10.1001/jama.2011.375. View

18.

Jakobsen M, Tolstrup M, Sogaard O, Jorgensen L, Gorry P, Laursen A . Transmission of HIV-1 drug-resistant variants: prevalence and effect on treatment outcome. Clin Infect Dis. 2010; 50(4):566-73. DOI: 10.1086/650001. View

19.

Simen B, Simons J, Hullsiek K, Novak R, MacArthur R, Baxter J . Low-abundance drug-resistant viral variants in chronically HIV-infected, antiretroviral treatment-naive patients significantly impact treatment outcomes. J Infect Dis. 2009; 199(5):693-701. DOI: 10.1086/596736. View

20.

Iglesias-Ussel M, Casado C, Yuste E, Olivares I, Lopez-Galindez C . In vitro analysis of human immunodeficiency virus type 1 resistance to nevirapine and fitness determination of resistant variants. J Gen Virol. 2001; 83(Pt 1):93-101. DOI: 10.1099/0022-1317-83-1-93. View