1 GRADE tables: What ARV regimen to start in children ≥ 3 years old? (TDF)

(1)

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

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

serious¹ serious² none 44/48

(91.7%)

48/49 (98%)

RR 0.94 (0.85 to 1.03)

29 more)

⊕⊕OO LOW

IMPORTANT

1 ART-experienced children switched to TDF-based regimens.

2 Few events.

3 Very few events.

(2)

2

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)

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

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

none 32/46

(69.6%)

33/44 (75%)

RR 0.93 (0.72 to 1.2)

150 more)

⊕OOO VERY LOW

CRITICAL

Study retention (follow-up 48 weeks)

1 randomized

trials

none 27/46

(58.7%)

29/44 (65.9%)

RR 0.89 (0.65 to 1.23)

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.

(3)

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

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 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

very serious¹

none 24 24 - Mean difference 1 higher

⊕⊕OO LOW

CRITICAL

BMI at week 96 (Better indicated by lower values)

1 randomized

trials

very serious¹

none 24 24 - Mean difference 0.7 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.

(4)

4

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

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

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

none 14/14

(100%)

13/14 (92.9%)

RR 1.07 (0.89 to 1.3)

279 more)

⊕OOO VERY LOW

CRITICAL

Study retention (follow-up 48 weeks)

1 randomized

trials¹

none 14/14

(100%)

13/14 (92.9%)

RR 1.07 (0.89 to 1.3)

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.