Nucleoside reverse-transcriptase inhibitor cross-resistance and outcomes from second-line antiretroviral therapy in the public health approach: an observational analysis within the randomised, open-label, EARNEST trial

The Lancet. HIV
Nicholas I PatonEurope Africa Research Network for Evaluation of Second-line Therapy (EARNEST) Trial Team

Abstract

Cross-resistance after first-line antiretroviral therapy (ART) failure is expected to impair activity of nucleoside reverse-transcriptase inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for the effect of cross-resistance on virological outcomes is limited. We aimed to assess the association between the activity, predicted by resistance testing, of the NRTIs used in second-line therapy and treatment outcomes for patients infected with HIV. We did an observational analysis of additional data from a published open-label, randomised trial of second-line ART (EARNEST) in sub-Saharan Africa. 1277 adults or adolescents infected with HIV in whom first-line ART had failed (assessed by WHO criteria with virological confirmation) were randomly assigned to a boosted protease inhibitor (standardised to ritonavir-boosted lopinavir) with two to three NRTIs (clinician-selected, without resistance testing); or with raltegravir; or alone as protease inhibitor monotherapy (discontinued after week 96). We tested genotypic resistance on stored baseline samples in patients in the protease inhibitor and NRTI group and calculated the predicted activity of prescribed second-line NRTIs. We measured viral load in stored samp...Continue Reading

Associated Clinical Trials

References

Oct 6, 2005·The Journal of Infectious Diseases·Steven G DeeksJeffrey N Martin
Mar 27, 2012·The Journal of Infectious Diseases·Kim C E SigaloffUNKNOWN PharmAccess African Studies to Evaluate Resistance (PASER)
Sep 7, 2013·PLoS Computational Biology·Niko BeerenwinkelUNKNOWN Swiss HIV Cohort Study
Nov 5, 2013·AIDS Research and Human Retroviruses·Sarah B LloydWendy R Winnall
Jul 12, 2014·The New England Journal of Medicine·Nicholas I PatonUNKNOWN EARNEST Trial Team
Aug 22, 2014·Journal of the International AIDS Society·Awachana JiamsakulUNKNOWN TREAT Asia Studies to Evaluate Resistance – Monitoring Study (TASER-M)
Oct 13, 2016·The Journal of Infectious Diseases·Ellen WhiteUNKNOWN UK HIV Drug Resistance Database and UK Collaborative HIV Cohort Study

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Citations

May 13, 2017·The Lancet. HIV·Gary Maartens, Graeme Meintjes
Jul 31, 2018·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jennifer A ThompsonUNKNOWN Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST) Trial Team
Jul 8, 2019·The Journal of Antimicrobial Chemotherapy·Soo-Yon RheeRobert W Shafer
Dec 1, 2017·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Thabo Ishmael LejoneNiklaus D Labhardt
Jan 14, 2020·HIV Medicine·O T StirrupUNKNOWN UK HIV Drug Resistance Database and the UK Collaborative HIV Cohort
Apr 18, 2018·AIDS Research and Therapy·Oliver T StirrupUNKNOWN UK Collaborative HIV Cohort
Dec 6, 2017·The Journal of Infectious Diseases·Elliot RaizesDeborah Birx
Jul 22, 2021·The New England Journal of Medicine·Nicholas I PatonUNKNOWN NADIA Trial Team

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Methods Mentioned

BETA
genotyping

Software Mentioned

EARNEST
stata

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