WHO/HIV/2013.40 © World Health Organization 2013
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 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 Inconsistency Indirectness Imprecision Other considerations
Children be switched to TDF-
based regimens
Maintained on AZT or d4T-based regimens among 2- to 16-year-olds
Relative
(95% CI) Absolute Virological response (VL < 50 copies) (follow-up 48 weeks)
1 randomized trials
no serious risk of bias
no serious inconsistency
serious1 serious2 none 34/48
(70.8%)
42/49 (85.7%)
RR 0.83 (0.67 to 1.02)
146 fewer per 1000 (from 283 fewer to
17 more)
⊕⊕OO LOW
CRITICAL
ART discontinuation (follow-up 48 weeks) 1 randomized
trials
no serious risk of bias
no serious inconsistency
serious1 very serious3
none 3/48
(6.3%)
2/49 (4.1%)
RR 1.53 (0.27 to 8.76)
22 more per 1000 (from 30 fewer to
317 more)
⊕OOO VERY LOW
CRITICAL
Study retention (follow-up 48 weeks) 1 randomized
trials
no serious risk of bias
no serious inconsistency
serious1 serious2 none 44/48
(91.7%)
48/49 (98%)
RR 0.94 (0.85 to 1.03)
59 fewer per 1000 (from 147 fewer to
29 more)
⊕⊕OO LOW
IMPORTANT
1 ART-experienced children switched to TDF-based regimens.
2 Few events.
3 Very few events.
WHO/HIV/2013.40 © World Health Organization 2013
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
2
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 IndirectnessImprecision 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
trials
no serious risk of bias
no serious inconsistency
serious1 very serious2
none 1/46
(2.2%)
0/44 (0%)
RR 2.87 (0.12 to 68.68)
- ⊕OOO
VERY LOW
CRITICAL
Viral suppression (follow-up 48 weeks)
1 randomized
trials
no serious risk of bias
no serious 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 VERY LOW
CRITICAL
Study retention (follow-up 48 weeks)
1 randomized
trials
no serious risk of bias
no serious inconsistency
serious1 very serious2
none 27/46
(58.7%)
29/44 (65.9%)
RR 0.89 (0.65 to 1.23)
73 fewer per 1000 (from 231 fewer to
152 more)
⊕OOO VERY LOW
CRITICAL
1 ART-experienced children who added TDF or placebo added to genotype-guided optimized background regimens.
2 Very few events.
WHO/HIV/2013.40 © World Health Organization 2013
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
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
QualityImportance No. of
studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations
TDF + EFV (comparison)
PI + d4T (reference)
Relative (95%
CI)
Absolute
CD4% at week 96 (better indicated by higher values)
1 randomized
trials
no serious risk of bias
no serious inconsistency
no serious indirectness
very serious1
none 24 24 - Mean difference 1.8 higher
(1.99 lower to 5.59 higher)
⊕⊕OO LOW
CRITICAL
CD4 count at week 96 (better indicated by higher values)
1 randomized
trials
no serious risk of bias
no serious inconsistency
no serious indirectness
very serious1
none 24 24 - Mean difference 1 higher
(171.01 lower to 173.01 higher)
⊕⊕OO LOW
CRITICAL
BMI at week 96 (Better indicated by lower values)
1 randomized
trials
no serious risk of bias
no serious inconsistency
no serious indirectness
very serious1
none 24 24 - Mean difference 0.7 higher
(1.03 lower to 2.43 higher)
⊕⊕OO LOW
CRITICAL
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.
WHO/HIV/2013.40 © World Health Organization 2013
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
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 IndirectnessImprecision Other considerations
Switched to TDF at baseline
switched to TDF at 24 weeks among 5- to 17-
year-olds
Relative
(95% CI) Absolute
Morbidity (follow-up 48 weeks)
1 randomized
trials1
no serious risk of bias
no serious 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 risk of bias
no serious inconsistency
serious2 very serious3
none 14/14
(100%)
13/14 (92.9%)
RR 1.07 (0.89 to 1.3)
65 more per 1000 (from 102 fewer to
279 more)
⊕OOO VERY LOW
CRITICAL
Study retention (follow-up 48 weeks)
1 randomized
trials1
no serious risk of bias
no serious inconsistency
serious2 very serious3
none 14/14
(100%)
13/14 (92.9%)
RR 1.07 (0.89 to 1.3)
65 more per 1000 (from 102 fewer to
279 more)
⊕OOO VERY LOW
IMPORTANT
1 Children were randomized to switch to TDF at baseline or 24 weeks.
2 ART-experienced children switched to TDF-based regimens and study conducted in Italy.
3 Very few events.
