Steve Kanters1, Maria Eugenia Socias2, Nicholas I Paton3, Marco Vitoria4, Meg Doherty4, Dieter Ayers5, Evan Popoff5, Keith Chan5, David A Cooper6, Matthew O Wiens7, Alexandra Calmy8, Nathan Ford4, Sabin Nsanzimana9, Edward J Mills10. 1. Precision Global Health, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada. 2. Precision Global Health, Vancouver, BC, Canada; Intersdisciplinary Graduate Program, University of British Columbia, Vancouver, BC, Canada. 3. Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 4. Department of HIV/AIDS, WHO, Geneva, Switzerland. 5. Precision Global Health, Vancouver, BC, Canada. 6. Kirby Institute, University of New South Wales, Sydney, NSW, Australia. 7. Precision Global Health, Vancouver, BC, Canada; Department of Medicine, University of British Columbia, Vancouver, BC, Canada. 8. HIV/AIDS Unit, Division of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland. 9. Institute of HIV Disease Prevention and Control, Rwanda Biomedical Centre, Kigali, Rwanda; Basel Clinical Epidemiology and Biostatistics Institute and Swiss Tropical and Public Health Institute, University of Basel, Switzerland. 10. Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada. Electronic address: millsej@mcmaster.ca.
Abstract
BACKGROUND: Selection of optimal second-line antiretroviral therapy (ART) has important clinical and programmatic implications. To inform the 2016 revision of the WHO ART guidelines, we assessed the comparative effectiveness and safety of available second-line ART regimens for adults and adolescents in whom first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens have failed. METHODS: In this systematic review and network meta-analysis, we searched for randomised controlled trials and prospective and retrospective cohort studies that evaluated outcomes in treatment-experienced adults living with HIV who switched ART regimen after failure of a WHO-recommended first-line NNRTI-based regimen. We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials for reports published from Jan 1, 1996, to Aug 8, 2016, and searched conference abstracts published from Jan 1, 2014, to Aug 8, 2016. Outcomes of interest were viral suppression, mortality, AIDS-defining illnesses or WHO stage 3-4 disease, discontinuations, discontinuations due to adverse events, and serious adverse events. We assessed comparative efficacy and safety in a network meta-analysis, using Bayesian hierarchical models. FINDINGS: We identified 12 papers pertaining to eight studies, including 4778 participants. The network was centred on ritonavir-boosted lopinavir plus two nucleoside or nucleotide reverse transcriptase inhibitors. Ritonavir-boosted lopinavir monotherapy was the only regimen inferior to others. With the lower estimate of the 95% credible interval (CrI) not exceeding the predefined threshold of 15%, evidence at 48 weeks supported the non-inferiority of ritonavir-boosted lopinavir plus raltegravir to regimens including ritonavir-boosted protease inhibitor plus two NRTIs with respect to viral suppression (odds ratio 1·09, 95% CrI 0·88-1·35). Estimated efficacy of ritonavir-boosted darunavir (800 mg once daily) was too imprecise to determine non-inferiority. Overall, regimens did not differ significantly with respect to continuations, AIDS-defining illnesses or WHO stage 3-4 disease, or mortality. INTERPRETATION: With the exception of ritonavir-boosted lopinavir plus raltegravir, the evidence base is unable to provide strong support to alternative second-line options to ritonavir-boosted protease inhibitor plus two NRTIs, and thus more trials are warranted. FUNDING: WHO.
BACKGROUND: Selection of optimal second-line antiretroviral therapy (ART) has important clinical and programmatic implications. To inform the 2016 revision of the WHO ART guidelines, we assessed the comparative effectiveness and safety of available second-line ART regimens for adults and adolescents in whom first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens have failed. METHODS: In this systematic review and network meta-analysis, we searched for randomised controlled trials and prospective and retrospective cohort studies that evaluated outcomes in treatment-experienced adults living with HIV who switched ART regimen after failure of a WHO-recommended first-line NNRTI-based regimen. We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials for reports published from Jan 1, 1996, to Aug 8, 2016, and searched conference abstracts published from Jan 1, 2014, to Aug 8, 2016. Outcomes of interest were viral suppression, mortality, AIDS-defining illnesses or WHO stage 3-4 disease, discontinuations, discontinuations due to adverse events, and serious adverse events. We assessed comparative efficacy and safety in a network meta-analysis, using Bayesian hierarchical models. FINDINGS: We identified 12 papers pertaining to eight studies, including 4778 participants. The network was centred on ritonavir-boosted lopinavir plus two nucleoside or nucleotide reverse transcriptase inhibitors. Ritonavir-boosted lopinavir monotherapy was the only regimen inferior to others. With the lower estimate of the 95% credible interval (CrI) not exceeding the predefined threshold of 15%, evidence at 48 weeks supported the non-inferiority of ritonavir-boosted lopinavir plus raltegravir to regimens including ritonavir-boosted protease inhibitor plus two NRTIs with respect to viral suppression (odds ratio 1·09, 95% CrI 0·88-1·35). Estimated efficacy of ritonavir-boosted darunavir (800 mg once daily) was too imprecise to determine non-inferiority. Overall, regimens did not differ significantly with respect to continuations, AIDS-defining illnesses or WHO stage 3-4 disease, or mortality. INTERPRETATION: With the exception of ritonavir-boosted lopinavir plus raltegravir, the evidence base is unable to provide strong support to alternative second-line options to ritonavir-boosted protease inhibitor plus two NRTIs, and thus more trials are warranted. FUNDING: WHO.
Authors: Paige L Williams; Katharine Correia; Brad Karalius; Russell B Van Dyke; James D Wilkinson; William T Shearer; Steven D Colan; Steven E Lipshultz Journal: AIDS Date: 2018-10-23 Impact factor: 4.177
Authors: Min Seo Kim; Dawon Seong; Han Li; Seo Kyoung Chung; Youngjoo Park; Minho Lee; Seung Won Lee; Dong Keon Yon; Jae Han Kim; Keum Hwa Lee; Marco Solmi; Elena Dragioti; Ai Koyanagi; Louis Jacob; Andreas Kronbichler; Kalthoum Tizaoui; Sarah Cargnin; Salvatore Terrazzino; Sung Hwi Hong; Ramy Abou Ghayda; Joaquim Radua; Hans Oh; Karel Kostev; Shuji Ogino; I-Min Lee; Edward Giovannucci; Yvonne Barnett; Laurie Butler; Daragh McDermott; Petre-Cristian Ilie; Jae Il Shin; Lee Smith Journal: Rev Med Virol Date: 2022-02-26 Impact factor: 11.043
Authors: Marta Iglis Oliveira; Valter Romão de Souza Junior; Claudia Fernanda de Lacerda Vidal; Paulo Sérgio Ramos de Araújo Journal: BMC Infect Dis Date: 2018-10-12 Impact factor: 3.090
Authors: R Horne; E Glendinning; K King; T Chalder; C Sabin; A S Walker; L J Campbell; I Mosweu; J Anderson; S Collins; R Jopling; P McCrone; H Leake Date; S Michie; M Nelson; N Perry; J A Smith; W Sseruma; V Cooper Journal: BMC Public Health Date: 2019-07-08 Impact factor: 3.295
Authors: Alexander J Stockdale; Matthew J Saunders; Mark A Boyd; Laura J Bonnett; Victoria Johnston; Gilles Wandeler; Annelot F Schoffelen; Laura Ciaffi; Kristen Stafford; Ann C Collier; Nicholas I Paton; Anna Maria Geretti Journal: Clin Infect Dis Date: 2018-06-01 Impact factor: 9.079