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
<h4>Background</h4> <p>Cross-resistance after first-line antiretroviral treatment (ART) failure is expected to impair activity of nucleoside-reverse-transcriptase-inhibitors (NRTIs) in second-line therapy, but evidence for effect on virological outcomes is limited.</p> <h...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Published: |
Elsevier
2017
|
| _version_ | 1797076261527355392 |
|---|---|
| author | Paton, N Kityo, C Thompson, J Nankya, I Bagenda, L Hoppe, A Hakim, J Kambugu, A van Oosterhout, J Kinconco, M Bertagnolio, S Easterbrook, P Mugyenyi, P Walker, A |
| author_facet | Paton, N Kityo, C Thompson, J Nankya, I Bagenda, L Hoppe, A Hakim, J Kambugu, A van Oosterhout, J Kinconco, M Bertagnolio, S Easterbrook, P Mugyenyi, P Walker, A |
| author_sort | Paton, N |
| collection | OXFORD |
| description | <h4>Background</h4> <p>Cross-resistance after first-line antiretroviral treatment (ART) failure is expected to impair activity of nucleoside-reverse-transcriptase-inhibitors (NRTIs) in second-line therapy, but evidence for effect on virological outcomes is limited.</p> <h4>Methods</h4> <p>We performed an observational analysis of a randomised-controlled trial of second-line ART (EARNEST) in sub-Saharan Africa. 1277 HIV-infected adults/adolescents failing first-line ART (WHO criteria, virological confirmation) were randomised to a boosted protease-inhibitor (PI; standardised to lopinavir/ritonavir) with either 2/3 NRTIs (clinician-selected, without resistance testing; PI/NRTI); raltegravir (PI/RAL); or as monotherapy (PI-mono; discontinued after week 96). Predicted activity of prescribed second-line NRTIs was determined by genotypic resistance testing on stored baseline samples in PI/NRTI. Viral load was measured on stored samples in all patients obtained every 12-16 weeks.</p> <h4>Findings</h4> <p>Baseline genotypes were available in 391 (92%) in PI/NRTI. For the 230 (59%) taking no predicted-active NRTIs, there was a high rate of VL suppression (89%(176/198) <400 copies per mL at week-144), superior to PI/RAL (81%(312/383) at week 144; P=0.02) and PI-mono (61%(233/280) at week-96; P<0.0001). VL suppression was no better with 1 predicted-active NRTI (85%(95/112), P=0.3 vs no active NRTIs) and appeared worse with 2-3 predicted active NRTIs (77%(20/26), P=0.08 vs no active NRTIs). Over all follow-up, greater predicted NRTI activity was associated with worse VL suppression (global p=0.0004). </p> <h4>Interpretation</h4> <p>Genotypic resistance testing may not accurately predict NRTI activity in PI-based second-line ART. Our results do not support the introduction of routine resistance testing in ART programmes in low-income settings for the purpose of selecting second-line NRTIs.</p> |
| first_indexed | 2024-03-07T00:01:37Z |
| format | Journal article |
| id | oxford-uuid:7626d7e6-beca-4a7e-92cb-4512e0bd0f5b |
| institution | University of Oxford |
| last_indexed | 2024-03-07T00:01:37Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:7626d7e6-beca-4a7e-92cb-4512e0bd0f5b2022-03-26T20:13:58ZNucleoside 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 trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7626d7e6-beca-4a7e-92cb-4512e0bd0f5bSymplectic Elements at OxfordElsevier2017Paton, NKityo, CThompson, JNankya, IBagenda, LHoppe, AHakim, JKambugu, Avan Oosterhout, JKinconco, MBertagnolio, SEasterbrook, PMugyenyi, PWalker, A <h4>Background</h4> <p>Cross-resistance after first-line antiretroviral treatment (ART) failure is expected to impair activity of nucleoside-reverse-transcriptase-inhibitors (NRTIs) in second-line therapy, but evidence for effect on virological outcomes is limited.</p> <h4>Methods</h4> <p>We performed an observational analysis of a randomised-controlled trial of second-line ART (EARNEST) in sub-Saharan Africa. 1277 HIV-infected adults/adolescents failing first-line ART (WHO criteria, virological confirmation) were randomised to a boosted protease-inhibitor (PI; standardised to lopinavir/ritonavir) with either 2/3 NRTIs (clinician-selected, without resistance testing; PI/NRTI); raltegravir (PI/RAL); or as monotherapy (PI-mono; discontinued after week 96). Predicted activity of prescribed second-line NRTIs was determined by genotypic resistance testing on stored baseline samples in PI/NRTI. Viral load was measured on stored samples in all patients obtained every 12-16 weeks.</p> <h4>Findings</h4> <p>Baseline genotypes were available in 391 (92%) in PI/NRTI. For the 230 (59%) taking no predicted-active NRTIs, there was a high rate of VL suppression (89%(176/198) <400 copies per mL at week-144), superior to PI/RAL (81%(312/383) at week 144; P=0.02) and PI-mono (61%(233/280) at week-96; P<0.0001). VL suppression was no better with 1 predicted-active NRTI (85%(95/112), P=0.3 vs no active NRTIs) and appeared worse with 2-3 predicted active NRTIs (77%(20/26), P=0.08 vs no active NRTIs). Over all follow-up, greater predicted NRTI activity was associated with worse VL suppression (global p=0.0004). </p> <h4>Interpretation</h4> <p>Genotypic resistance testing may not accurately predict NRTI activity in PI-based second-line ART. Our results do not support the introduction of routine resistance testing in ART programmes in low-income settings for the purpose of selecting second-line NRTIs.</p> |
| spellingShingle | Paton, N Kityo, C Thompson, J Nankya, I Bagenda, L Hoppe, A Hakim, J Kambugu, A van Oosterhout, J Kinconco, M Bertagnolio, S Easterbrook, P Mugyenyi, P Walker, A 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 |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| work_keys_str_mv | AT patonn nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT kityoc nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT thompsonj nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT nankyai nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT bagendal nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT hoppea nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT hakimj nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT kambugua nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT vanoosterhoutj nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT kinconcom nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT bertagnolios nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT easterbrookp nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT mugyenyip nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial AT walkera nucleosidereversetranscriptaseinhibitorcrossresistanceandoutcomesfromsecondlineantiretroviraltherapyinthepublichealthapproachanobservationalanalysiswithintherandomisedopenlabelearnesttrial |