Adverse events associated with nevirapine use in pregnancy: a systematic review and meta-analysis Nathan Ford,

(1)

WHO/HIV/2013.54 © World Health Organization 2013

Adverse events associated with nevirapine use in pregnancy: a systematic review and meta-analysis Nathan Ford,

^1,2

Alexandra Calmy,

^1,3

Isabelle Andrieux-Meyer,

¹

Sally Hargreaves,

⁴

Edward J Mills,

⁵

Zara Shubber.

⁶

1. Médecins Sans Frontières, 78 rue de Lausanne, 1211 Geneva, Switzerland

2. Centre for Infectious Disease Epidemiology and Research, University of Cape Town, South Africa 3. HIV/AIDS Unit, Infectious Disease Service, Geneva University Hospital, Geneva. Switzerland.

4. The International Health Unit, Department of Infectious Diseases and Immunity, Hammersmith Hospital, Imperial College London, London, United Kingdom 5. Faculty of Health Sciences, University of Ottawa, Ottawa, Canada

6. Department of Epidemiology and Biostatistics, Faculty of Medicine, Imperial College, London, UK.

Correspondence: Dr Nathan Ford, Médecins Sans Frontières78 rue de Lausanne, 1211 Geneva, Switzerland. Email: [email protected]

GRADE table: Assessment of the quality of evidence: comparison of adverse events at CD4 cell count >250 cells/mm

³

vs to

≤

250 cells/mm

³

Quality assessment No of patients Effect

Quality Importance No of

studies Design Risk of

bias Inconsistency Indirectness Imprecision Other considerations

>250

cells/mm3 ≤250 cells/mm3

Relative

(95% CI) Absolute Hepatotoxicity overall

14 observational studies

serious¹ no serious inconsistency²

no serious indirectness

very serious³

none 169/1856

(9.1%)

68/833 (8.2%)

OR 0.88 (0.65 to 1.19)

9 fewer per 1000 (from 27 fewer to

14 more)

⊕ΟΟΟ VERY LOW

IMPORTANT

0% -

Severe hepatotoxicity 14 observational

studies

serious¹ no serious inconsistency⁴

very serious⁵

none 80/1856

(4.3%)

20/833 (2.4%)

OR 1.45 (0.91 to 2.32)

11 more per 1000 (from 2 fewer to 32

more)

⊕ΟΟΟ VERY LOW

CRITICAL

0% -

Rash overall

(2)

WHO/HIV/2013.54 © World Health Organization 2013

Quality assessment No of patients Effect

Quality Importance No of

studies Design Risk of

bias Inconsistency Indirectness Imprecision Other considerations

>250

cells/mm3 ≤250 cells/mm3

Relative

(95% CI) Absolute 14 observational

studies

serious¹ no serious inconsistency²

very serious⁵

none 118/1305

(9%)

50/712 (7%)

OR 1.25 (0.87 to 1.80)

more)

⊕ΟΟΟ VERY LOW

IMPORTANT

0% -

Severe rash

12 observational studies

serious⁶ no serious inconsistency²

very serious⁵

none 50/1201

(4.2%)

20/626 (3.2%)

OR 1.41 (0.82 to 2.42)

more)

⊕ΟΟΟ VERY LOW

CRITICAL

0% -

Hypersensitivity reaction 4 observational

studies

very serious⁷

no serious inconsistency²

very serious⁵

none 100/543

(18.4%)

30/158 (19%)

OR 0.94 (0.60 to 1.48)

9 fewer per 1000 (from 67 fewer to

68 more)

⊕ΟΟΟ VERY LOW

IMPORTANT

0% -

1 6 of 14 studies retrospective in design; 7 studies rated as at high risk of bias

2 No statistical heterogeneity (I-squared = 0.0)

3 Tendency towards a significant result but lower bound still crosses the null. Results for all but 1 study crossed the null

4 Low statistical heterogeneity (I-squared = 0.7%)

5 Wide confidence intervals consistent with an appreciably greater number of adverse events in either CD4 group; no individual study report a statistically significant difference between CD4 groups

6 No explanation was provided

7 3 of 4 studies retrospective in design and rated as at high risk of bias