WHO/HIV/2013.40
© World Health Organization 2013
GRADE tables: What ARV regimen to start in children ≥3 years old? (TDF) RANDOMIZED CONTROLLED TRIALS Author(s): George Rutherford, Alicen B. Spaulding Date: 2012-11-25 Question: Should children ≥3 years old be switched to TDF-based regimens versus maintained on AZT or d4T-based regimens for HIV treatment after initial suppression? Settings: Panama, United Kingdom, United States Bibliography: Gilead 2012 (GS-US-104-0352)
Quality assessment
No. of patients
Effect Quality Importance
No. of studies
Design
Risk of bias
Children be Maintained on AZT or Other Relative Inconsistency Indirectness Imprecision switched to TDFd4T-based regimens considerations (95% CI) based regimens among 2- to 16-year-olds
Absolute
Virological response (VL < 50 copies) (follow-up 48 weeks) 1 randomized no serious no serious trials risk of inconsistency bias serious1 serious2 none 34/48 (70.8%) 42/49 (85.7%) RR 0.83 146 fewer per 1000 ⊕⊕OO (0.67 to (from 283 fewer to LOW 1.02) 17 more) CRITICAL
ART discontinuation (follow-up 48 weeks) 1 randomized no serious no serious trials risk of inconsistency bias serious1 very serious3 none 3/48 (6.3%) 2/49 (4.1%) RR 1.53 (0.27 to 8.76) 22 more per 1000 ⊕OOO (from 30 fewer to VERY 317 more) LOW CRITICAL
Study retention (follow-up 48 weeks) 1 randomized no serious no serious trials risk of inconsistency bias serious1 serious2 none 44/48 (91.7%) 48/49 (98%) RR 0.94 (0.85 to 1.03) 59 fewer per 1000 ⊕⊕OO IMPORTANT (from 147 fewer to LOW 29 more)
1 2
ART-experienced children switched to TDF-based regimens. Few events. 3 Very few events.
This work was commissioned by the World Health Organization and carried out by The University of California, San Francisco (UCSF), Cochrane Review Group on HIV/AIDS
1
WHO/HIV/2013.40
© World Health Organization 2013
Author(s): George Rutherford, Alicen B. Spaulding Date: 2012-11-25 Question: Should ART-experienced 12- to-17-year-old children have TDF added to genotype-guided optimized background regimens? Settings: Brazil, Panama Bibliography: Gilead 2012 (GS-US-104-0321)
Quality assessment
No. of patients
Effect Quality Importance
No. of studies
Design
Risk of bias
Inconsistency Indirectness Imprecision
Other considerations
Switched to TDF-based regimens
maintain current regimen among 12-17 year olds
Relative (95% CI)
Absolute
Serious adverse event or death (follow-up 48 weeks) 1 randomized no serious no serious trials risk of bias inconsistency serious1 very serious2 none 1/46 (2.2%) 0/44 (0%) RR 2.87 (0.12 to 68.68) ⊕OOO CRITICAL VERY LOW
Viral suppression (follow-up 48 weeks) 1 randomized no serious no serious trials risk of bias inconsistency serious1 very serious2 none 32/46 (69.6%) 33/44 (75%) RR 0.93 (0.72 to 1.2) 52 fewer per 1000 (from 210 fewer to 150 more) ⊕OOO CRITICAL VERY LOW
Study retention (follow-up 48 weeks) 1 randomized no serious no serious trials risk of bias inconsistency serious1 very serious2 none 27/46 (58.7%) 29/44 (65.9%) 73 fewer per 1000 RR 0.89 (0.65 to 1.23) (from 231 fewer to 152 more) ⊕OOO CRITICAL VERY LOW
1 2
ART-experienced children who added TDF or placebo added to genotype-guided optimized background regimens. Very few events.
This work was commissioned by the World Health Organization and carried out by The University of California, San Francisco (UCSF), Cochrane Review Group on HIV/AIDS
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WHO/HIV/2013.40
© World Health Organization 2013
Author(s): Anglemyer A, Horvath T, Rutherford G Date: 2012-11-27 Question: Should children ≥3 years old living with HIV initiate d4T + PI or TDF + EFV-based triple antiretroviral therapy? Settings: Italy Bibliography: Viganò 2007
Quality assessment
No. of patients
Effect Quality Importance
No. of studies
Design
Risk of bias
Inconsistency
Indirectness
TDF + EFV PI + d4T Relative Other Imprecision (95% considerations (comparison) (reference) CI)
Absolute
CD4% at week 96 (better indicated by higher values) 1 randomized trials no serious risk of no serious bias inconsistency no serious indirectness very serious1 none 24 24 Mean difference 1.8 higher ⊕⊕OO CRITICAL (1.99 lower to 5.59 higher) LOW
CD4 count at week 96 (better indicated by higher values) 1 randomized trials no serious risk of no serious bias inconsistency no serious indirectness very serious1 none 24 24 Mean difference 1 higher ⊕⊕OO CRITICAL (171.01 lower to 173.01 LOW higher)
BMI at week 96 (Better indicated by lower values) 1 randomized trials no serious risk of no serious bias inconsistency no serious indirectness very serious1 none 24 24 Mean difference 0.7 higher ⊕⊕OO CRITICAL (1.03 lower to 2.43 higher) LOW
1
A sample size of only 24. This study randomized children who were virally suppressed on d4T + PI therapy to switch to TDF + EFV or continue on d4T + PI.
This work was commissioned by the World Health Organization and carried out by The University of California, San Francisco (UCSF), Cochrane Review Group on HIV/AIDS
3
WHO/HIV/2013.40
© World Health Organization 2013
Author(s): George Rutherford, Alicen B. Spaulding Date: 2012-11-25 Question: Should children be switched to TDF at baseline versus switched to TDF at 24 weeks among 5- to 17-year-olds for HIV treatment in children? Settings: Italy Bibliography: Vigano 2005
Quality assessment
No. of patients
Effect Quality Importance
No. of studies
Design
Risk of bias
Inconsistency Indirectness Imprecision
Other considerations
Switched to TDF at baseline
switched to TDF at 24 Relative weeks among 5- to 17(95% CI) year-olds
Absolute
Morbidity (follow-up 48 weeks) 1 randomized trials1 no serious no serious risk of bias inconsistency serious2 very serious3 none 0/14 (0%) 0/14 (0%) not pooled not pooled ⊕OOO VERY LOW CRITICAL
Immunologic response (VL <50 copies) (follow-up 48 weeks) 1 randomized trials1 no serious no serious risk of bias inconsistency serious2 very serious3 none 14/14 (100%) 13/14 (92.9%) RR 1.07 65 more per 1000 (0.89 to 1.3) (from 102 fewer to 279 more) ⊕OOO VERY LOW CRITICAL
Study retention (follow-up 48 weeks) 1 randomized trials1 no serious no serious risk of bias inconsistency serious2 very serious3 none 14/14 (100%) 13/14 (92.9%) RR 1.07 65 more per 1000 (0.89 to 1.3) (from 102 fewer to 279 more) ⊕OOO IMPORTANT VERY LOW
1 2
Children were randomized to switch to TDF at baseline or 24 weeks. ART-experienced children switched to TDF-based regimens and study conducted in Italy. 3 Very few events.
This work was commissioned by the World Health Organization and carried out by The University of California, San Francisco (UCSF), Cochrane Review Group on HIV/AIDS
4