GRADE table: What ARV regimen to switch to in children younger than 3 years old?

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WHO/HIV/2013.34 © World Health Organization 2013

GRADE table: What ARV regimen to switch to in children younger than 3 years old?

Author(s): Penazzato M.

Date: 2012-11-29

Question: Should infants and young children starting a PI-based regimen be switched to NNRTI once virological suppression is achieved versus continuing PI?

Settings: resource-limited settings

Bibliography: Coovadia et al. 2008, Kuhn et al. 2012

Quality assessment No. of patients Effect

Quality Importance No. of

studies Design Risk of

bias Inconsistency Indirectness Imprecision Other considerations

Switching to NNRTI once virological

suppression is achieved

Continuing PI

Relative

(95% CI) Absolute

Virological failure at 52 weeks (follow-up 156 weeks; assessed with: any VL>50 copies/ml)

1 randomized trials

no serious risk of bias

no serious inconsistency

Very serious¹

no serious imprecision

none 40/96

(41.7%)

55/99 (55.6%)

HR 0.62 (0.41 to 0.92)²

160 fewer per 1000 (from 30 fewer to 273

fewer)

⊕⊕ΟΟ LOW

CRITICAL

Virological failure at 52 weeks (safety endpoint) (follow-up 156 weeks; assessed with: confirmed VL>1000 copies/ml)

1 randomized trials

Very serious¹

none 18/96

(18.8%)

2/99 (2%)

HR 10.19 (2.36 to 43.94)³

168 more per 1000 (from 27 more to 572

more)

⊕⊕ΟΟ LOW

CRITICAL

Decline by 10% in CD4% by 52 weeks (follow-up 156 weeks; assessed with: CD4%)

1 randomized trials

Very serious¹

none 3/96

(3.1%)

14/99 (14.1%)

RR 0.22 (0.07 to 0.74)⁴

110 fewer per 1000 (from 37 fewer to 132

fewer)

⊕⊕ΟΟ LOW

CRITICAL

Decline by 1 z-score in weight-for-age by 52 weeks (follow-up 156 weeks; assessed with: confirmed VL>1000 copies/ml)

1 randomized no no serious Very no serious none 4/96 13/99 RR 0.32 89 fewer per ⊕⊕ΟΟ IMPORTANT

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WHO/HIV/2013.34 © World Health Organization 2013

trials serious risk of bias

inconsistency serious¹ imprecision (4.2%) (13.1%) (0.11 to

0.94)⁵

1000 (from 8 fewer to 117

fewer)

LOW

Highest ALT (grade 3/4) (follow-up 156 weeks)

1 randomized trials

Very serious¹

serious⁶ none 7/96

(7.3%)

4/99 (4%)

RR 13.66 (5.15 to 36.29)⁶

512 more per 1000 (from 168

more to 1000 more)

⊕ΟΟΟ VERY LOW

CRITICAL

Lowest neutropaenia (grade 3/4) (follow-up 156 weeks)

1 randomized trials

Very serious¹

serious⁷ none 5/96

(5.2%)

3/99 (3%)

RR 1.72 (0.42 to 6.99)⁷

22 more per 1000 (from 18

fewer to 182 more)

⊕ΟΟΟ VERY LOW

CRITICAL

1 The findings may not be easily generalizable since enrolled children had all achieved and sustained viral load <400 copies/ml for at least 3 months within the first 12 months of treatment. This selected population is likely to have better adherence, fewer problems with ART tolerability and an improved prognosis, compared to an unselected population. In addition, evidence was further downgraded as the only trial available to inform this question used NVP and it is unclear whether the same results would be achieved with EFV.

2 P = 0.02.

3 Strong evidence indicates that virological failure is 10 times higher in the intervention arm (P = 0.002).

4 P = 0.01.

5 P = 0.04.

6 Small number of events, likely to be unpowered to assess this difference (P = 0.33).

7 Small number of events, likely to be unpowered to assess this difference (P = 0.45).