New antiretroviral agents efficacy and safety. Rilpivirine Elvitegravir Both agents with Truvada,+/- cobicistat (not in search terms)
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1 Appendix 4 BHIVA Treatment Guideline update 20 Search protocol: main databases search: rilpivirine and elvitegravir Component Review area Objectives Populations Description New antiretroviral agents efficacy and safety Safety and efficacy of rilpivirine and elvitegravir HIV infected, naïve to ART Adults all questions Interventions Comparisons/aspects covered by search Outcomes Rilpivirine Elvitegravir Both agents with Truvada,+/- cobicistat (not in search terms) Truvada and efavirenz; ritonavir/atazanavir; any other ART regimens (terms not in search) To be decided by writing groups to include: Virological suppression to <50 copies/ml, virological failure, discontinuation due to AEs, grade 3/4 AEs, HIV drug resistance Study designs Exclusions How the information was searched All studies Animal studies, letters, editorials, comments, non-english studies Databases: Medline, Embase, Cochrane Library Language: restrict to English only Date parameters: 2011 to current Search terms and date searched HIV + (rilpivirine OR elvitegravir) Medline = 121 Embase = 0 Search results Cochrane = 11 Total=2 Total deduplicated = 185
2 Forest plot of comparison: 2 Stribild versus efavirenz, outcome: 2.1 Confirmed virological response (<50 copies/ml) weeks Stribild Efavirenz Risk Ratio Risk Ratio Cohen 2011 AIDS % 1.08 [0.88, 1.34] Sax 2012 Lancet % 1.03 [0.97, 1.10] 1.04 [0.98, 1.10] Heterogeneity: Chi² = 0.19, df = 1 (P = 0.66); I² = 0% Test for overall effect: Z = 1.16 (P = 0.25) weeks Zolopa 20 (Sax) [0.96, 1.09] 1.02 [0.96, 1.09] 292 Test for overall effect: Z = 0.64 (P = 0.52) weeks Study [0.98, 1.15] 1.06 [0.98, 1.15] 279 Test for overall effect: Z = 1.55 (P = 0.12) Test for subgroup differences: Chi² = 0.61, df = 2 (P = 0.74), I² = 0% Favours efavirenz
3 Forest plot of comparison: 2 Stribild versus efavirenz, outcome: 2.2 Discontinued due to adverse event weeks Stribild Efavirenz Risk Ratio Risk Ratio Cohen 2011 AIDS % 0.16 [0.01, 3.86] Sax 2012 Lancet % 0.73 [0.36, 1.47] 0.67 [0.34, 1.32] 19 Heterogeneity: Chi² = 0.82, df = 1 (P = 0.36); I² = 0% Test for overall effect: Z = 1.15 (P = 0.25) weeks Zolopa 20 (Sax) [0.38, 1.25] 0.69 [0.38, 1.25] 17 Test for overall effect: Z = 1.23 (P = 0.22) 25 Test for subgroup differences: Chi² = 0.00, df = 1 (P = 0.96), I² = 0% Favours efavirenz
4 Forest plot of comparison: 2 Stribild versus efavirenz, outcome: 2.3 Virological failure weeks Stribild Efavirenz Risk Ratio Risk Ratio Cohen 2011 AIDS % 0.16 [0.01, 3.86] Sax 2012 Lancet % 1.28 [0.62, 2.66] 1.12 [0.56, 2.25] 16 Heterogeneity: Chi² = 1.55, df = 1 (P = 0.21); I² = 36% Test for overall effect: Z = 0.33 (P = 0.74) weeks Study [0.48, 1.42] 0.82 [0.48, 1.42] 22 Test for overall effect: Z = 0.70 (P = 0.49) weeks Study [0.47, 1.] 0.77 [0.47, 1.] Test for overall effect: Z = 1.03 (P = 0.30) 34 Test for subgroup differences: Chi² = 0.78, df = 2 (P = 0.68), I² = 0% Favours efavirenz
5 Forest plot of comparison: 3 Stribild versus atazanavir, outcome: 3.1 Confirmed virological response (<50 copies/ml) weeks Stribild Atazanavir Risk Ratio Risk Ratio DeJesus 2012 Lancet [0.96, 1.08] 1.02 [0.96, 1.08] 304 Test for overall effect: Z = 0.50 (P = 0.62) weeks Rockstroh 20 (DeJesus) [0.95, 1.08] 1.01 [0.95, 1.08] 293 Test for overall effect: Z = 0.36 (P = 0.72) weeks Study [0.96, 1.] 1.04 [0.96, 1.] 274 Test for overall effect: Z = 0.93 (P = 0.35) Test for subgroup differences: Chi² = 0.27, df = 2 (P = 0.87), I² = 0% Favours atanazavir
6 Forest plot of comparison: 3 Stribild versus atazanavir, outcome: 3.2 Discontinued due to adverse event weeks Stribild Atazanavir Risk Ratio Risk Ratio DeJesus 2012 Lancet [0.36, 1.46] 0.73 [0.36, 1.46] Test for overall effect: Z = 0.90 (P = 0.37) weeks Rockstroh 20 (DeJesus) [0.35, 1.30] 0.67 [0.35, 1.30] 14 Test for overall effect: Z = 1.19 (P = 0.24) 21 Test for subgroup differences: Chi² = 0.03, df = 1 (P = 0.87), I² = 0% Favours atazanavir
7 Forest plot of comparison: 3 Stribild versus atazanavir, outcome: 3.3 Virological failure weeks Stribild Atazanavir Risk Ratio Risk Ratio DeJesus 2012 Lancet [0.41, 3.04] 1.11 [0.41, 3.04] 8 Test for overall effect: Z = 0.21 (P = 0.83) weeks Study [0.54, 1.58] 0.93 [0.54, 1.58] 24 Test for overall effect: Z = 0.27 (P = 0.79) weeks Study [0.65, 1.81] 1.08 [0.65, 1.81] 28 Test for overall effect: Z = 0.30 (P = 0.76) Test for subgroup differences: Chi² = 0.20, df = 2 (P = 0.90), I² = 0% Favours atazanavir
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