GRADE tables: What ARV regimen to switch to in adults, pregnant women, adolescents and children living with HIV (once-daily PI regimens)?

Transcription

1 GRADE tables: What ARV regimen to switch to in adults, pregnant women, adolescents and children living with HIV (once-daily PI regimens)? ATZ/r versus LPV/r Author(s): Larry W Chang, Alicen B Spaulding, George W Rutherford Date: Question: Should ATZ/r vs LPV/r be used for HIV treatment failure? Settings: Low and Middle-Income Countries Bibliography: BMS 045 (2005, 2006) assessment patients Effect Design Risk Inconsistency Indirectness Imprecision ATZ/r LPV/r Mortality (96 Weeks) risk,2,3 serious none 0/120 4 (0%) 2/123 (1.6%) RR 0.2 (0.01 to 4.23) 13 fewer per 1000 (from 16 fewer to 53 Viral response (intent to treat, time to loss of viral response, <50 copies/ml, noncompleter = failure, 96 weeks) risk,2,3 serious none 39/120 44/123 4 (32.5%) (35.8%) RR 0.91 (0.64 to 1.29) 32 fewer per 1000 (from 129 fewer to 104 Severe adverse events (96 weeks) risk,2,3 serious none 16/120 13/123 4 (13.3%) (10.6%) RR 1.26 (0.63 to 2.51) 27 more per 1000 (from 39 fewer to 160 Immune response (96 weeks) risk,2,3 serious none Median increase, 160 cells/mm 3 4 versus 142 cells/mm 3 Retention on treatment (96 weeks) risk,2,3 serious none 67/120 65/123 4 (55.8%) (52.8%) RR 1.06 (0.84 to 1.33) 32 more per 1000 (from 85 fewer to 174 1

2 1 The study was conducted primarily in high-income countries. 2 The regimens previously failing participants differed significantly from WHO first-line regimens, both in quantity and in content. 3 The NRTI backbones used in new regimen included tenofovir and another NRTI selected with guidance from phenotypic sensitivity testing, an option not available in most low- and middle-income settings. 4 Very few events. DRV/r versus LPV/r Author(s): Larry W. Chang, Alicen B. Spaulding, George W. Rutherford Date: Question: DRV/r versus LPV/r or boosted PI for second-line ART Settings: Low- and middle-income countries Bibliography: POWER (2007, 2009); TITAN (2007, 2012) assessment patients Effect Design Risk of bias Inconsistency Indirectness Imprecision DRV/r LPV/r or boosted PI Mortality (48 Weeks) risk 5 serious 6 none 7/429 (1.6%) 4/421 (0.95%) RR 1.7 (0.5 to 5.81) 7 more per 1000 (from 5 fewer to 46 Virologic Response (intent to treat, time to loss of viral response, <50 copies/ml, 96 weeks) risk 5 none 231/429 (53.8%) 175/421 (41.6%) RR 1.31 (1.14 to 1.5) 129 more per 1000 (from 58 more to 208 O Severe adverse events (48 weeks) risk 5 serious 6 none 54/429 (12.6%) 48/421 (11.4%) RR 1.1 (0.76 to 1.58) 11 more per 1000 (from 27 fewer to 66 Immune response (96 weeks) (better indicated by higher values) risk,2,3,4,5 none First trial = median increase from baseline, 81 cells/mm 3 versus 93 cells/mm 3 ; second trial = mean absolute increase, 133 cells/mm 3 versus 15 cells/mm 3 On Treatment Retention (48 Weeks) 2

3 risk 5 none 339/429 (79%) 235/421 (55.8%) RR 1.42 (1.29 to 1.57) 234 more per 1000 (from 162 more to 318 O 1 The study was conducted primarily in high-income countries. 2 The regimens previously failing participants differed significantly from WHO first-line regimens, both in quantity and in content. 3 DRV/r was twice-daily 600 mg/100 mg dosing rather than daily dosing. 4 Comparison group in POWER 1, 2 included a mix of boosted PIs; only 36% were on a LPV/r-based regimen. 5 NRTI backbones were used in a new regimen selected using resistance testing data and may have included antiretroviral drugs not typically available in most low- and middle-income settings. 6 Very few events. Use of ATZ/r or DRV/r in first-line regimens Author(s): George W. Rutherford, Tara Horvath Date: Question: ATV/r versus LPV/r for second-line antiretroviral therapy among people living with HIV (first-line therapy ) Settings: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Columbia, Costa Rica, France, Germany, Hong Kong SAR, Indonesia, Italy, Mexico, Netherlands, Norway, Panama, Peru, Portugal, Puerto Rico, Singapore, Spain, South Africa, Sweden, Thailand, United Kingdom, United States Bibliography: Molina 2008, Molina 2010, Josephson 2010 assessment patients Effect Design Risk Inconsistency Indirectness Imprecision ATV/r LPV/r Mortality (96 weeks) risk serious 2 none 6/440 (1.4%) 5/443 (1.1%) RR 1.21 (0.37 to 3.93) 2 more per 1000 (from 7 fewer to 33 Plasma VL <50 copies/ml (96 weeks) risk none 326/ /443 (74.1%) (66.6%) RR 1.09 (1 to 1.19) 60 more per 1000 (from 0 more to 127 O Plasma VL <50 copies/ml (48 weeks) risk none 405/ /508 (79.7%) (78.7%) RR 1.01 (0.95 to 1.08) 8 more per 1000 (from 39 fewer to 63 O Increase in CD4 cells/mm 3 (96 weeks) (better indicated by higher values) 3

4 risk none Mean difference 21.2 lower (43.3 lower to 0.9 higher) O Severe adverse events (96 weeks) risk serious 3 none 62/441 48/437 (14.1%) (11%) RR 1.28 (0.9 to 1.82) 31 more per 1000 (from 11 fewer to 90 Retained in care (96 weeks) risk serious 3 none 72/438 95/440 (16.4%) (21.6%) RR 1.07 (1 to 1.14) 15 more per 1000 (from 0 more to 30 <100% adherence (self-report) (96 weeks) risk,4 none 361/ /443 RR 0.98 (0.92 to (82%) (84%) 1.04) 17 fewer per 1000 (from 67 fewer to 34 1 First-line therapy. 2 Very few events. 3 Few events. 4 Self-report. Author(s): George W. Rutherford, Tara Horvath Date: Question: DRV/r versus LPV/r for second-line antiretroviral therapy among people living with HIV (first-line therapy ) Settings: Argentina, Australia, Austria, Belgium, Canada, Chile, Costa Rica, Denmark, France, Germany, Greece, Guatemala, Italy, Malaysia, Mexico, Panama, Puerto Rico, Russian Federation, Singapore, South Africa, Spain, Switzerland, Taiwan, China, Thailand, United Kingdom, United States Bibliography: Orkin 2012 assessment patients Effect Design Risk Inconsistency Indirectness Imprecision DRV/r LPV/r Mortality (192 weeks) risk serious 2 none 4/343 (1.2%) 7/346 (2%) RR 0.58 (0.17 to 1.95) 8 fewer per 1000 (from 17 fewer to 19 Plasma VL <50 copies/ml (192 weeks) 4

5 risk none 236/ /346 (68.8%) (57.2%) RR 1.2 (1.07 to 1.35) 114 more per 1000 (from 40 more to 200 O Increase in CD4 cells/mm 3 (192 weeks) (better indicated by higher values) risk none Mean difference 5 lower (19.93 lower to 9.93 higher) O 1 grade 3 or 4 adverse events (192 weeks) risk serious 3 none 103/ /346 RR 0.94 (0.76 to (30%) (31.8%) 1.18) 19 fewer per 1000 (from 76 fewer to 57 >95% adherence (Modified Medication Adherence Self-Report Inventory) (192 weeks) risk none 286/ /346 (83.4%) (78.3%) RR 1.06 (0.99 to 1.15) 47 more per 1000 (from 8 fewer to 117 O 1 First-line therapy. 2 Very few events. 3 Few events. 5