Volume 4, Issue 10, Pages e433-e441 (October 2017)

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Volume 4, Issue 10, Pages e433-e441 (October 2017) Comparative efficacy and safety of second-line antiretroviral therapy for treatment of HIV/AIDS: a systematic review and network meta-analysis Steve Kanters, MSc, Maria Eugenia Socias, MD, Prof Nicholas I Paton, MD, Marco Vitoria, MD, Meg Doherty, MD, Dieter Ayers, MSc, Evan Popoff, MSc, Keith Chan, MSc, Prof David A Cooper, MD, Matthew O Wiens, PhD, Prof Alexandra Calmy, MD, Nathan Ford, PhD, Sabin Nsanzimana, MD, Dr Edward J Mills, PhD The Lancet HIV Volume 4, Issue 10, Pages e433-e441 (October 2017) DOI: 10.1016/S2352-3018(17)30109-1 Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 1 Flow diagram of included studies The Lancet HIV 2017 4, e433-e441DOI: (10.1016/S2352-3018(17)30109-1) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 2 Network of evidence for second-line antiretroviral therapy Each node (circle) represents an individual antiretroviral therapy regimen, each line represents availability of head-to-head evidence between two treatments, and the study names on the lines indicate the studies informing each head-to-head comparison. Solid lines represent cohorts not from randomised controlled trials. Dashed lines represent connections with patients with failure of NNRTIs that are not necessarily first-line regimens. DRV/r=ritonavir-boosted darunavir. NRTI=nucleoside or nucleotide reverse transcriptase inhibitor. LPV/r=ritonavir-boosted lopinavir. RAL=raltegravir. IDV/r=ritonavir-boosted indinavir. ATV/r=ritonavir-boosted atazanavir. SQV=saquinavir. The Lancet HIV 2017 4, e433-e441DOI: (10.1016/S2352-3018(17)30109-1) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 3 Forest plots for viral suppression and mortality for second-line treatment comparisons Each odds ratio represents the effect of the first treatment relative to the second treatment in people with HIV with previous NNRTI-based ART failure. Higher odds ratios are desired for viral suppression, whereas lower ones are desired for mortality. CrI=credible interval. LPV/r=ritonavir-boosted lopinavir. NRTI=nucleoside or nucleotide reverse transcriptase inhibitor. ATV/r=ritonavir-boosted atazanavir. DRV/r=ritonavir-boosted darunavir. RAL=raltegravir. The Lancet HIV 2017 4, e433-e441DOI: (10.1016/S2352-3018(17)30109-1) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 4 Fixed-effects network meta-analysis of change from baseline in CD4 cell count Data are mean difference (95% CrI) of the row treatment relative to the column treatment (eg, the difference in mean CD4 cell count for LPV/r vs LPV/r plus two NRTIs was 23·93 cells per μL). Bold values indicate comparisons that are statistically significant. CrI=credible interval. LPV/r=ritonavir-boosted lopinavir. NRTI=nucleoside or nucleotide reverse transcriptase inhibitor. RAL=raltegravir. SQV=saquinavir. ATV/r=ritonavir-boosted atazanavir. IDV/r=ritonavir-boosted indinavir. The Lancet HIV 2017 4, e433-e441DOI: (10.1016/S2352-3018(17)30109-1) Copyright © 2017 Elsevier Ltd Terms and Conditions

Figure 5 Forest plots for discontinuations, discontinuations because of adverse events, and serious adverse events for second-line treatment comparisons Each odds ratio represents the effect of the first treatment relative to the second treatment in people with HIV with previous failure of ART based on a non-nucleoside reverse transcriptase inhibitor. Lower odds ratios are desired for listed outcomes. CrI=credible interval. LPV/r=ritonavir-boosted lopinavir. DRV/r=ritonavir-boosted darunavir. NRTI=nucleoside or nucleotide reverse transcriptase inhibitor. RAL=raltegravir. The Lancet HIV 2017 4, e433-e441DOI: (10.1016/S2352-3018(17)30109-1) Copyright © 2017 Elsevier Ltd Terms and Conditions