Skip to main content
Top
Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | Research article

Use of reverse-transcriptase-based HIV-1 viral load assessment to confirm low viral loads in newly diagnosed patients in Switzerland

Authors: Beatrice N Vetter, Cyril Shah, Jon B Huder, Jürg Böni, Jörg Schüpbach

Published in: BMC Infectious Diseases | Issue 1/2014

Login to get access

Abstract

Background

Treatment-naïve patients newly diagnosed with HIV occasionally present with low viral RNA of ≤1’000 copies/ml, raising concerns about viral load underestimation. Because falsely low or undetectable viral loads might lead to inadvertent virus transmission or treatment delays, confirmation of such cases by a sequence-independent viral load test is recommended in Switzerland.

Methods

HIV-1 RNA ≤1’000 cp/ml by Roche’s or Abbott’s tests in patients newly diagnosed from 2010 to 2012 in Switzerland were subjected to viral load testing by the product-enhanced-reverse transcriptase (PERT) assay. These investigations were complemented with repeat and/or alternative viral RNA measurements.

Results

HIV-1 RNA ≤1’000 cp/ml was observed in 71 of 1814 newly diagnosed patients. The PERT assay suggested clinically relevant viral load underestimation in 7 of 32 cases that could be investigated. In four patients, the PERT viral load was 10-1’000-fold higher; this was confirmed by alternative HIV-1 RNA tests. Six of the 7 underestimates had been obtained with meanwhile outdated versions of Roche’s HIV-1 RNA test. In the seventh patient, follow-up revealed similar results for RNA and PERT based viral loads.

Conclusion

PERT assay revealed occasional severe viral load underestimation by versions of HIV-1 RNA tests meanwhile outdated. Underestimation by contemporary tests appears rare, however.
Appendix
Available only for authorised users
Literature
1.
go back to reference Cobb BR, Vaks JE, Do T, Vilchez RA: Evolution in the sensitivity of quantitative HIV-1 viral load tests. J Clin Virol. 2011, 52: S77-S82.CrossRefPubMed Cobb BR, Vaks JE, Do T, Vilchez RA: Evolution in the sensitivity of quantitative HIV-1 viral load tests. J Clin Virol. 2011, 52: S77-S82.CrossRefPubMed
2.
go back to reference Gueudin M, Plantier JC, Lemee V, Schmitt MP, Chartier L, Bourlet T, Ruffault A, Damond F, Vray M, Simon F: Evaluation of the Roche Cobas TaqMan and Abbott RealTime extraction-quantification systems for HIV-1 subtypes. J Acquir Immune Defic Syndr. 2007, 44: 500-505. 10.1097/QAI.0b013e31803260df.CrossRefPubMed Gueudin M, Plantier JC, Lemee V, Schmitt MP, Chartier L, Bourlet T, Ruffault A, Damond F, Vray M, Simon F: Evaluation of the Roche Cobas TaqMan and Abbott RealTime extraction-quantification systems for HIV-1 subtypes. J Acquir Immune Defic Syndr. 2007, 44: 500-505. 10.1097/QAI.0b013e31803260df.CrossRefPubMed
3.
go back to reference Wirden M, Tubiana R, Marguet F, Leroy I, Simon A, Bonmarchand M, Ait-Arkoub Z, Murphy R, Marcelin AG, Katlama C, Calvez V: Impact of discrepancies between the Abbott realtime and cobas TaqMan assays for quantification of human immunodeficiency virus type 1 group M non-B subtypes. J Clin Microbiol. 2009, 47: 1543-1545. 10.1128/JCM.02134-08.CrossRefPubMedPubMedCentral Wirden M, Tubiana R, Marguet F, Leroy I, Simon A, Bonmarchand M, Ait-Arkoub Z, Murphy R, Marcelin AG, Katlama C, Calvez V: Impact of discrepancies between the Abbott realtime and cobas TaqMan assays for quantification of human immunodeficiency virus type 1 group M non-B subtypes. J Clin Microbiol. 2009, 47: 1543-1545. 10.1128/JCM.02134-08.CrossRefPubMedPubMedCentral
4.
go back to reference SFOPH: Das schweizerische HIV-Testkonzept – aktualisierte Übersicht über Technisches Konzept und Laborkonzept. 2006, Bulletin 51, 1029- SFOPH: Das schweizerische HIV-Testkonzept – aktualisierte Übersicht über Technisches Konzept und Laborkonzept. 2006, Bulletin 51, 1029-
5.
go back to reference Pyra H, Boni J, Schupbach J: Ultrasensitive retrovirus detection by a reverse transcriptase assay based on product enhancement. Proc Natl Acad Sci U S A. 1994, 91: 1544-1548. 10.1073/pnas.91.4.1544.CrossRefPubMedPubMedCentral Pyra H, Boni J, Schupbach J: Ultrasensitive retrovirus detection by a reverse transcriptase assay based on product enhancement. Proc Natl Acad Sci U S A. 1994, 91: 1544-1548. 10.1073/pnas.91.4.1544.CrossRefPubMedPubMedCentral
6.
go back to reference Boni J, Pyra H, Schupbach J: Sensitive detection and quantification of particle-associated reverse transcriptase in plasma of HIV-1-infected individuals by the product-enhanced reverse transcriptase (PERT) assay. J Med Virol. 1996, 49: 23-28. 10.1002/(SICI)1096-9071(199605)49:1<23::AID-JMV4>3.0.CO;2-M.CrossRefPubMed Boni J, Pyra H, Schupbach J: Sensitive detection and quantification of particle-associated reverse transcriptase in plasma of HIV-1-infected individuals by the product-enhanced reverse transcriptase (PERT) assay. J Med Virol. 1996, 49: 23-28. 10.1002/(SICI)1096-9071(199605)49:1<23::AID-JMV4>3.0.CO;2-M.CrossRefPubMed
7.
go back to reference Burgisser P, Vernazza P, Flepp M, Boni J, Tomasik Z, Hummel U, Pantaleo G, Schupbach J: Performance of five different assays for the quantification of viral load in persons infected with various subtypes of HIV-1. Swiss HIV Cohort Study. J Acquir Immune Defic Syndr. 2000, 23: 138-144. 10.1097/00126334-200002010-00005.CrossRefPubMed Burgisser P, Vernazza P, Flepp M, Boni J, Tomasik Z, Hummel U, Pantaleo G, Schupbach J: Performance of five different assays for the quantification of viral load in persons infected with various subtypes of HIV-1. Swiss HIV Cohort Study. J Acquir Immune Defic Syndr. 2000, 23: 138-144. 10.1097/00126334-200002010-00005.CrossRefPubMed
8.
go back to reference Labbett W, Garcia-Diaz A, Fox Z, Clewley GS, Fernandez T, Johnson M, Geretti AM: Comparative evaluation of the ExaVir Load version 3 reverse transcriptase assay for measurement of human immunodeficiency virus type 1 plasma load. J Clin Microbiol. 2009, 47: 3266-3270. 10.1128/JCM.00715-09.CrossRefPubMedPubMedCentral Labbett W, Garcia-Diaz A, Fox Z, Clewley GS, Fernandez T, Johnson M, Geretti AM: Comparative evaluation of the ExaVir Load version 3 reverse transcriptase assay for measurement of human immunodeficiency virus type 1 plasma load. J Clin Microbiol. 2009, 47: 3266-3270. 10.1128/JCM.00715-09.CrossRefPubMedPubMedCentral
9.
go back to reference Schupbach J, Gebhardt MD, Scherrer AU, Bisset LR, Niederhauser C, Regenass S, Yerly S, Aubert V, Suter F, Pfister S, Martinetti G, Andreutti C, Klimkait T, Brandenberger M, Günthard HF, Swiss HIV Cohort Study: Simple estimation of incident HIV infection rates in notification cohorts based on window periods of algorithms for evaluation of line-immunoassay result patterns. PLoS One. 2013, 8: e71662-10.1371/journal.pone.0071662.CrossRefPubMedPubMedCentral Schupbach J, Gebhardt MD, Scherrer AU, Bisset LR, Niederhauser C, Regenass S, Yerly S, Aubert V, Suter F, Pfister S, Martinetti G, Andreutti C, Klimkait T, Brandenberger M, Günthard HF, Swiss HIV Cohort Study: Simple estimation of incident HIV infection rates in notification cohorts based on window periods of algorithms for evaluation of line-immunoassay result patterns. PLoS One. 2013, 8: e71662-10.1371/journal.pone.0071662.CrossRefPubMedPubMedCentral
10.
go back to reference Schupbach J, Gebhardt MD, Tomasik Z, Niederhauser C, Yerly S, Burgisser P, Matter L, Gorgievski M, Dubs R, Schultze D, Steffen I, Andreutti C, Martinetti G, Güntert B, Staub R, Daneel S, Vernazza P: Assessment of recent HIV-1 infection by a line immunoassay for HIV-1/2 confirmation. PLoS Med. 2007, 4: e343-10.1371/journal.pmed.0040343.CrossRefPubMedPubMedCentral Schupbach J, Gebhardt MD, Tomasik Z, Niederhauser C, Yerly S, Burgisser P, Matter L, Gorgievski M, Dubs R, Schultze D, Steffen I, Andreutti C, Martinetti G, Güntert B, Staub R, Daneel S, Vernazza P: Assessment of recent HIV-1 infection by a line immunoassay for HIV-1/2 confirmation. PLoS Med. 2007, 4: e343-10.1371/journal.pmed.0040343.CrossRefPubMedPubMedCentral
11.
go back to reference SFOPH: HIV- und STI-Fallzahlen 2012: Berichterstattung, Analysen und Trends. 2013, Bundesamt für Gesundheit: Bulletin 21, 376-3003 Bern, Switzerland SFOPH: HIV- und STI-Fallzahlen 2012: Berichterstattung, Analysen und Trends. 2013, Bundesamt für Gesundheit: Bulletin 21, 376-3003 Bern, Switzerland
13.
go back to reference Glaubitz J, Sizmann D, Simon CO, Hoffmann KS, Drogan D, Hesse M, Lang G, Kroeh M, Simmler P, Dewald M, Haberhausen G, Lindauer A, Beyser K, Reber A, Baumeister A, Wolf E, Jaeger H, Babiel R: Accuracy to 2nd international HIV-1 RNA WHO Standard: assessment of three generations of quantitative HIV-1 RNA nucleic acid amplification tests. J Clin Virol. 2011, 50: 119-124. 10.1016/j.jcv.2010.10.017.CrossRefPubMed Glaubitz J, Sizmann D, Simon CO, Hoffmann KS, Drogan D, Hesse M, Lang G, Kroeh M, Simmler P, Dewald M, Haberhausen G, Lindauer A, Beyser K, Reber A, Baumeister A, Wolf E, Jaeger H, Babiel R: Accuracy to 2nd international HIV-1 RNA WHO Standard: assessment of three generations of quantitative HIV-1 RNA nucleic acid amplification tests. J Clin Virol. 2011, 50: 119-124. 10.1016/j.jcv.2010.10.017.CrossRefPubMed
14.
go back to reference Holguin A, Lopez M, Molinero M, Soriano V: Performance of three commercial viral load assays, Versant human immunodeficiency virus type 1 (HIV-1) RNA bDNA v3.0, Cobas AmpliPrep/Cobas TaqMan HIV-1, and NucliSens HIV-1 EasyQ v1.2, testing HIV-1 non-B subtypes and recombinant variants. J Clin Microbiol. 2008, 46: 2918-2923. 10.1128/JCM.02414-07.CrossRefPubMedPubMedCentral Holguin A, Lopez M, Molinero M, Soriano V: Performance of three commercial viral load assays, Versant human immunodeficiency virus type 1 (HIV-1) RNA bDNA v3.0, Cobas AmpliPrep/Cobas TaqMan HIV-1, and NucliSens HIV-1 EasyQ v1.2, testing HIV-1 non-B subtypes and recombinant variants. J Clin Microbiol. 2008, 46: 2918-2923. 10.1128/JCM.02414-07.CrossRefPubMedPubMedCentral
15.
go back to reference Karasi JC, Dziezuk F, Quennery L, Forster S, Reischl U, Colucci G, Schoener D, Seguin-Devaux C, Schmit JC: High correlation between the Roche COBAS(R) AmpliPrep/COBAS(R) TaqMan(R) HIV-1, v2.0 and the Abbott m2000 RealTime HIV-1 assays for quantification of viral load in HIV-1 B and non-B subtypes. J Clin Virol. 2011, 52: 181-186. 10.1016/j.jcv.2011.07.002.CrossRefPubMed Karasi JC, Dziezuk F, Quennery L, Forster S, Reischl U, Colucci G, Schoener D, Seguin-Devaux C, Schmit JC: High correlation between the Roche COBAS(R) AmpliPrep/COBAS(R) TaqMan(R) HIV-1, v2.0 and the Abbott m2000 RealTime HIV-1 assays for quantification of viral load in HIV-1 B and non-B subtypes. J Clin Virol. 2011, 52: 181-186. 10.1016/j.jcv.2011.07.002.CrossRefPubMed
16.
go back to reference Taylor N, Schmid I, Egle A, Greil R, Patsch W, Oberkofler H: Initial evaluation of the Roche COBAS TaqMan HIV-1 v2.0 assay for determining viral load in HIV-infected individuals. Antivir Ther. 2009, 14: 1189-1193. 10.3851/IMP1427.CrossRefPubMed Taylor N, Schmid I, Egle A, Greil R, Patsch W, Oberkofler H: Initial evaluation of the Roche COBAS TaqMan HIV-1 v2.0 assay for determining viral load in HIV-infected individuals. Antivir Ther. 2009, 14: 1189-1193. 10.3851/IMP1427.CrossRefPubMed
17.
go back to reference Gray RH, Wawer MJ, Brookmeyer R, Sewankambo NK, Serwadda D, Wabwire-Mangen F, Lutalo T, Li X, van Cott T, Quinn TC, Team RP: Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet. 2001, 357: 1149-1153. 10.1016/S0140-6736(00)04331-2.CrossRefPubMed Gray RH, Wawer MJ, Brookmeyer R, Sewankambo NK, Serwadda D, Wabwire-Mangen F, Lutalo T, Li X, van Cott T, Quinn TC, Team RP: Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet. 2001, 357: 1149-1153. 10.1016/S0140-6736(00)04331-2.CrossRefPubMed
18.
go back to reference Pilcher CD, Tien HC, Eron JJ, Vernazza PL, Leu SY, Stewart PW, Goh LE, Cohen MS, Study Q, Consortium D-U-EAH: Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis. 2004, 189: 1785-1792. 10.1086/386333.CrossRefPubMed Pilcher CD, Tien HC, Eron JJ, Vernazza PL, Leu SY, Stewart PW, Goh LE, Cohen MS, Study Q, Consortium D-U-EAH: Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis. 2004, 189: 1785-1792. 10.1086/386333.CrossRefPubMed
19.
go back to reference Korn K, Weissbrich B, Henke-Gendo C, Heim A, Jauer CM, Taylor N, Eberle J: Single-point mutations causing more than 100-fold underestimation of human immunodeficiency virus type 1 (HIV-1) load with the Cobas TaqMan HIV-1 real-time PCR assay. J Clin Microbiol. 2009, 47: 1238-1240. 10.1128/JCM.02204-08.CrossRefPubMedPubMedCentral Korn K, Weissbrich B, Henke-Gendo C, Heim A, Jauer CM, Taylor N, Eberle J: Single-point mutations causing more than 100-fold underestimation of human immunodeficiency virus type 1 (HIV-1) load with the Cobas TaqMan HIV-1 real-time PCR assay. J Clin Microbiol. 2009, 47: 1238-1240. 10.1128/JCM.02204-08.CrossRefPubMedPubMedCentral
20.
go back to reference Sizmann D, Glaubitz J, Simon CO, Goedel S, Buergisser P, Drogan D, Hesse M, Kroh M, Simmler P, Dewald M, Gilsdorf M, Fuerst M, Ineichen R, Kirn A, Pasche P, Wang Z, Weisshaar S, Young K, Haberhausen G, Babiel R: Improved HIV-1 RNA quantitation by COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 using a novel dual-target approach. J Clin Virol. 2010, 49: 41-46. 10.1016/j.jcv.2010.06.004.CrossRefPubMed Sizmann D, Glaubitz J, Simon CO, Goedel S, Buergisser P, Drogan D, Hesse M, Kroh M, Simmler P, Dewald M, Gilsdorf M, Fuerst M, Ineichen R, Kirn A, Pasche P, Wang Z, Weisshaar S, Young K, Haberhausen G, Babiel R: Improved HIV-1 RNA quantitation by COBAS AmpliPrep/COBAS TaqMan HIV-1 Test, v2.0 using a novel dual-target approach. J Clin Virol. 2010, 49: 41-46. 10.1016/j.jcv.2010.06.004.CrossRefPubMed
21.
go back to reference Pas S, Rossen JW, Schoener D, Thamke D, Pettersson A, Babiel R, Schutten M: Performance evaluation of the new Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test version 2.0 for quantification of human immunodeficiency virus type 1 RNA. J Clin Microbiol. 2010, 48: 1195-1200. 10.1128/JCM.01832-09.CrossRefPubMedPubMedCentral Pas S, Rossen JW, Schoener D, Thamke D, Pettersson A, Babiel R, Schutten M: Performance evaluation of the new Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test version 2.0 for quantification of human immunodeficiency virus type 1 RNA. J Clin Microbiol. 2010, 48: 1195-1200. 10.1128/JCM.01832-09.CrossRefPubMedPubMedCentral
22.
go back to reference Sire JM, Vray M, Merzouk M, Plantier JC, Pavie J, Maylin S, Timsit J, Lascoux-Combe C, Molina JM, Simon F, Delaugerre C: Comparative RNA quantification of HIV-1 group M and non-M with the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 v2.0 and Abbott Real-Time HIV-1 PCR assays. J Acquir Immune Defic Syndr. 2011, 56: 239-243. 10.1097/QAI.0b013e3182099891.CrossRefPubMed Sire JM, Vray M, Merzouk M, Plantier JC, Pavie J, Maylin S, Timsit J, Lascoux-Combe C, Molina JM, Simon F, Delaugerre C: Comparative RNA quantification of HIV-1 group M and non-M with the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 v2.0 and Abbott Real-Time HIV-1 PCR assays. J Acquir Immune Defic Syndr. 2011, 56: 239-243. 10.1097/QAI.0b013e3182099891.CrossRefPubMed
Metadata
Title
Use of reverse-transcriptase-based HIV-1 viral load assessment to confirm low viral loads in newly diagnosed patients in Switzerland
Authors
Beatrice N Vetter
Cyril Shah
Jon B Huder
Jürg Böni
Jörg Schüpbach
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-84

Other articles of this Issue 1/2014

BMC Infectious Diseases 1/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.