Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial
<h4>Background</h4> <p>Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor (PI) plus raltegravir (RAL) as an alternative second-line c...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Elsevier
2017
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| _version_ | 1797053103506194432 |
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| author | Hakim, J Thompson, J Kityo, C Hoppe, A Kambugu, A van Oosterhout, J Lugemwa, A Siika, A Mwebaze, R Mweemba, A Abongomera, G Thomason, M Easterbrook, P Mugyenyi, P Walker, A Paton, N |
| author_facet | Hakim, J Thompson, J Kityo, C Hoppe, A Kambugu, A van Oosterhout, J Lugemwa, A Siika, A Mwebaze, R Mweemba, A Abongomera, G Thomason, M Easterbrook, P Mugyenyi, P Walker, A Paton, N |
| author_sort | Hakim, J |
| collection | OXFORD |
| description | <h4>Background</h4> <p>Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor (PI) plus raltegravir (RAL) as an alternative second-line combination. We assessed whether this offers any advantage over the standard PI plus two nucleoside-reverse-transcriptase-inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings.</p> <h4>Methods</h4> <p>We randomised 1277 HIV-infected adults/adolescents in 14 sites, 5 sub-Saharan African countries failing (WHO criteria, confirmed by viral load (VL) testing) non-NRTI-based first-line ART to receive PI (ritonavir-boosted lopinavir) plus 2/3 clinician-selected NRTIs (PI/NRTI group), PI plus RAL (PI/RAL group); or PI monotherapy (plus RAL induction for first 12 weeks; re-intensified to combination therapy after week 96; PI-mono). Randomisation was by computer-generated randomisation sequence, with variable block size. The main outcome was VL<400 copies/ml at week 144.</p> <h4>Findings</h4> <p>Patients were 58% female; baseline CD4 71 cells/mm3; 2% withdrew/were lost to follow-up. At 144 weeks on the primary (complete-case) analysis, 317 of 426 (86%) in PI/NRTI vs 312 of 433 (81%) in PI/RAL had VL<400 copies/ml (P=0.07; lower 95% confidence limit for difference 10.2% vs specified non-inferiority margin 10%). Findings varied on some secondary analyses (non-inferiority criteria were met on snapshot analysis), but there was no evidence supporting superiority of PI/RAL. In PI-mono, 292 of 418 (78%) had VL<400 copies/ml; P=0.003 vs PI/NRTI) at 144 weeks. There was no evidence of differences between groups in survival, WHO-4 events or adverse events. </p> <h4>Interpretation</h4> <p>PI/RAL offered no advantage over PI/NRTI in virogical efficacy or safety. On the primary analysis, PI/RAL narrowly failed to meet non-inferiority criteria and tended to produce inferior VL suppression at 144 weeks. A regimen of PI with NRTIs remains the best standardised second-line regimen for use in programmes in resource-limited settings.</p> |
| first_indexed | 2024-03-06T18:39:21Z |
| format | Journal article |
| id | oxford-uuid:0c5be2c4-4a7d-4395-a093-b952c8b5bfd9 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T18:39:21Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:0c5be2c4-4a7d-4395-a093-b952c8b5bfd92022-03-26T09:34:33ZLopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trialJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0c5be2c4-4a7d-4395-a093-b952c8b5bfd9Symplectic Elements at OxfordElsevier2017Hakim, JThompson, JKityo, CHoppe, AKambugu, Avan Oosterhout, JLugemwa, ASiika, AMwebaze, RMweemba, AAbongomera, GThomason, MEasterbrook, PMugyenyi, PWalker, APaton, N <h4>Background</h4> <p>Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor (PI) plus raltegravir (RAL) as an alternative second-line combination. We assessed whether this offers any advantage over the standard PI plus two nucleoside-reverse-transcriptase-inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings.</p> <h4>Methods</h4> <p>We randomised 1277 HIV-infected adults/adolescents in 14 sites, 5 sub-Saharan African countries failing (WHO criteria, confirmed by viral load (VL) testing) non-NRTI-based first-line ART to receive PI (ritonavir-boosted lopinavir) plus 2/3 clinician-selected NRTIs (PI/NRTI group), PI plus RAL (PI/RAL group); or PI monotherapy (plus RAL induction for first 12 weeks; re-intensified to combination therapy after week 96; PI-mono). Randomisation was by computer-generated randomisation sequence, with variable block size. The main outcome was VL<400 copies/ml at week 144.</p> <h4>Findings</h4> <p>Patients were 58% female; baseline CD4 71 cells/mm3; 2% withdrew/were lost to follow-up. At 144 weeks on the primary (complete-case) analysis, 317 of 426 (86%) in PI/NRTI vs 312 of 433 (81%) in PI/RAL had VL<400 copies/ml (P=0.07; lower 95% confidence limit for difference 10.2% vs specified non-inferiority margin 10%). Findings varied on some secondary analyses (non-inferiority criteria were met on snapshot analysis), but there was no evidence supporting superiority of PI/RAL. In PI-mono, 292 of 418 (78%) had VL<400 copies/ml; P=0.003 vs PI/NRTI) at 144 weeks. There was no evidence of differences between groups in survival, WHO-4 events or adverse events. </p> <h4>Interpretation</h4> <p>PI/RAL offered no advantage over PI/NRTI in virogical efficacy or safety. On the primary analysis, PI/RAL narrowly failed to meet non-inferiority criteria and tended to produce inferior VL suppression at 144 weeks. A regimen of PI with NRTIs remains the best standardised second-line regimen for use in programmes in resource-limited settings.</p> |
| spellingShingle | Hakim, J Thompson, J Kityo, C Hoppe, A Kambugu, A van Oosterhout, J Lugemwa, A Siika, A Mwebaze, R Mweemba, A Abongomera, G Thomason, M Easterbrook, P Mugyenyi, P Walker, A Paton, N Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial |
| title | Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial |
| title_full | Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial |
| title_fullStr | Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial |
| title_full_unstemmed | Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial |
| title_short | Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial |
| title_sort | lopinavir plus nucleoside reverse transcriptase inhibitors lopinavir plus raltegravir or lopinavir monotherapy for second line treatment of hiv earnest 144 week follow up results from a randomised controlled trial |
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