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Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients


Metzner, K J; Scherrer, A U; von Wyl, V; Böni, J; Yerly, S; Klimkait, T; Aubert, V; Furrer, H; Hirsch, H; Vernazza, P L; Cavassini, M; Calmy, A; Bernasconi, E; Weber, R; Gunthard, H F (2014). Limited clinical benefit of minority K103N and Y181C-variant detection in addition to routine genotypic resistance testing in antiretroviral therapy-naive patients. AIDS, 28(15):2231-2239.

Abstract

OBJECTIVE: The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients. DESIGN: We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing. METHODS: Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients. RESULTS: Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant. CONCLUSION: As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.

Abstract

OBJECTIVE: The presence of minority nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 variants prior to antiretroviral therapy (ART) has been linked to virologic failure in treatment-naive patients. DESIGN: We performed a large retrospective study to determine the number of treatment failures that could have been prevented by implementing minority drug-resistant HIV-1 variant analyses in ART-naïve patients in whom no NNRTI resistance mutations were detected by routine resistance testing. METHODS: Of 1608 patients in the Swiss HIV Cohort Study, who have initiated first-line ART with two nucleoside reverse transcriptase inhibitors (NRTIs) and one NNRTI before July 2008, 519 patients were eligible by means of HIV-1 subtype, viral load and sample availability. Key NNRTI drug resistance mutations K103N and Y181C were measured by allele-specific PCR in 208 of 519 randomly chosen patients. RESULTS: Minority K103N and Y181C drug resistance mutations were detected in five out of 190 (2.6%) and 10 out of 201 (5%) patients, respectively. Focusing on 183 patients for whom virologic success or failure could be examined, virologic failure occurred in seven out of 183 (3.8%) patients; minority K103N and/or Y181C variants were present prior to ART initiation in only two of those patients. The NNRTI-containing, first-line ART was effective in 10 patients with preexisting minority NNRTI-resistant HIV-1 variant. CONCLUSION: As revealed in settings of case-control studies, minority NNRTI-resistant HIV-1 variants can have an impact on ART. However, the implementation of minority NNRTI-resistant HIV-1 variant analysis in addition to genotypic resistance testing (GRT) cannot be recommended in routine clinical settings. Additional associated risk factors need to be discovered.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Uncontrolled Keywords:antiretroviral therapy, antiretroviral therapy-naive patients, drug resistance testing, minority drug-resistant HIV-1 variants, virological failure
Language:English
Date:24 September 2014
Deposited On:28 Nov 2014 14:04
Last Modified:18 Apr 2018 11:45
Publisher:Lippincott Williams & Wilkins
ISSN:0269-9370
Funders:SHCS (SHCS), supported by the Swiss National Science Foundation (SNF) (grant 33CS30_134277, SHCS research foundation, SNF grants 324700-120793 (to H.F.G. and K.J.M.), 320000-116035 and 324730-130865 (to H.F.G.), SHCS [project 605] (to H.F.G. and K.J.M.), University of Zurich’s Clinical Research Priority Programme (CRPP) ‘Viral infectious diseases: Zurich Primary HIV Infection Study’ (to H.F.G.), Yvonne-Jacob Foundation (to H.F.G.),, Unrestricted research grant from the Vontobel Stiftung (to H.F.G. and K.J.M.), Gilead (to H.F.G.)
OA Status:Hybrid
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1097/QAD.0000000000000397
PubMed ID:25036184
Project Information:
  • : FunderFP7
  • : Grant ID223131
  • : Project TitleCHAIN - Collaborative HIV and Anti-HIV Drug Resistance Network
  • : FunderSNSF
  • : Grant ID
  • : Project TitleSHCS (SHCS), supported by the Swiss National Science Foundation (SNF) (grant 33CS30_134277
  • : Funder
  • : Grant ID
  • : Project TitleSHCS research foundation
  • : FunderSNSF
  • : Grant ID
  • : Project TitleSNF grants 324700-120793 (to H.F.G. and K.J.M.), 320000-116035 and 324730-130865 (to H.F.G.)
  • : Funder
  • : Grant ID
  • : Project TitleSHCS [project 605] (to H.F.G. and K.J.M.)
  • : Funder
  • : Grant ID
  • : Project TitleUniversity of Zurich’s Clinical Research Priority Programme (CRPP) ‘Viral infectious diseases: Zurich Primary HIV Infection Study’ (to H.F.G.)
  • : Funder
  • : Grant ID
  • : Project TitleYvonne-Jacob Foundation (to H.F.G.),
  • : Funder
  • : Grant ID
  • : Project TitleUnrestricted research grant from the Vontobel Stiftung (to H.F.G. and K.J.M.)
  • : Funder
  • : Grant ID
  • : Project TitleGilead (to H.F.G.)

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