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Results of search
Figures and Tables -
Figure 1

Results of search

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
Figures and Tables -
Figure 2

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
Figures and Tables -
Figure 3

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 1 Virological success.
Figures and Tables -
Analysis 1.1

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 1 Virological success.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 2 Change in CD4 count.
Figures and Tables -
Analysis 1.2

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 2 Change in CD4 count.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 3 Mortality.
Figures and Tables -
Analysis 1.3

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 3 Mortality.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 4 Progression to AIDS.
Figures and Tables -
Analysis 1.4

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 4 Progression to AIDS.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 5 Discontinuation rate.
Figures and Tables -
Analysis 1.5

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 5 Discontinuation rate.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 6 Severe adverse events:Rash.
Figures and Tables -
Analysis 1.6

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 6 Severe adverse events:Rash.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 7 Severe adverse events:CNS.
Figures and Tables -
Analysis 1.7

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 7 Severe adverse events:CNS.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 8 Severe adverse events: GIT.
Figures and Tables -
Analysis 1.8

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 8 Severe adverse events: GIT.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 9 Severe adverse events: Pyrexia.
Figures and Tables -
Analysis 1.9

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 9 Severe adverse events: Pyrexia.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 10 Severe adverse events: Raised transaminases.
Figures and Tables -
Analysis 1.10

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 10 Severe adverse events: Raised transaminases.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 11 Severe adverse events: Raised alkaline phosphatase.
Figures and Tables -
Analysis 1.11

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 11 Severe adverse events: Raised alkaline phosphatase.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 12 Severe adverse events: Raised Amylase.
Figures and Tables -
Analysis 1.12

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 12 Severe adverse events: Raised Amylase.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 13 Severe adverse events: Raised Triglycerides.
Figures and Tables -
Analysis 1.13

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 13 Severe adverse events: Raised Triglycerides.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 14 Severe adverse events: Neutropenia.
Figures and Tables -
Analysis 1.14

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 14 Severe adverse events: Neutropenia.

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 15 All severe adverse events.
Figures and Tables -
Analysis 1.15

Comparison 1 Efavirenz 600mg versus Nevirapine 200mg twice daily, Outcome 15 All severe adverse events.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 1 Virological success.
Figures and Tables -
Analysis 2.1

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 1 Virological success.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 2 Change in CD4 count.
Figures and Tables -
Analysis 2.2

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 2 Change in CD4 count.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 3 Mortality.
Figures and Tables -
Analysis 2.3

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 3 Mortality.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 4 Progression to AIDS.
Figures and Tables -
Analysis 2.4

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 4 Progression to AIDS.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 5 Discontinuation rate.
Figures and Tables -
Analysis 2.5

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 5 Discontinuation rate.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 6 Severe adverse events: Rash.
Figures and Tables -
Analysis 2.6

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 6 Severe adverse events: Rash.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 7 Severe adverse events:CNS.
Figures and Tables -
Analysis 2.7

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 7 Severe adverse events:CNS.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 8 Severe adverse events: GIT.
Figures and Tables -
Analysis 2.8

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 8 Severe adverse events: GIT.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 9 Severe adverse events: Pyrexia.
Figures and Tables -
Analysis 2.9

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 9 Severe adverse events: Pyrexia.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 10 Severe adverse events: Raised transaminases.
Figures and Tables -
Analysis 2.10

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 10 Severe adverse events: Raised transaminases.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 11 Severe adverse events: Raised alkaline phosphatase.
Figures and Tables -
Analysis 2.11

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 11 Severe adverse events: Raised alkaline phosphatase.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 12 Severe adverse events: Raised Amylase.
Figures and Tables -
Analysis 2.12

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 12 Severe adverse events: Raised Amylase.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 13 Severe adverse events: Raised Triglycerides.
Figures and Tables -
Analysis 2.13

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 13 Severe adverse events: Raised Triglycerides.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 14 Severe adverse events: Raised cholesterol.
Figures and Tables -
Analysis 2.14

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 14 Severe adverse events: Raised cholesterol.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 15 Severe adverse events: Neutropenia.
Figures and Tables -
Analysis 2.15

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 15 Severe adverse events: Neutropenia.

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 16 All severe adverse events.
Figures and Tables -
Analysis 2.16

Comparison 2 Efavirenz 600mg versus Nevirapine 400mg once daily, Outcome 16 All severe adverse events.

Summary of findings for the main comparison. Efavirenz 600mg versus Nevirapine 200mg twice daily for initial treatment of HIV infection in antiretroviral‐naive individuals

Efavirenz 600mg versus Nevirapine 200mg twice daily for initial treatment of HIV infection in antiretroviral‐naive individuals

Patient or population: patients with initial treatment of HIV infection in antiretroviral‐naive individuals
Settings: Multiple locations
Intervention: Efavirenz 600mg versus Nevirapine 200mg twice daily

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Efavirenz 600mg versus Nevirapine 200mg twice daily

Virological success
Follow‐up: median 48 weeks

699 per 1000

713 per 1000
(664 to 769)

RR 1.02
(0.95 to 1.1)

1200
(4 studies)

⊕⊕⊕⊕
high1,2,3,4,5

Change in CD4 count
Follow‐up: median 48 weeks

The mean Change in CD4 count in the intervention groups was
2 lower
(23.17 lower to 19.18 higher)

1285
(5 studies)

⊕⊕⊕⊕
high1,3,4,5

Mortality
Follow‐up: median 48 weeks

55 per 1000

49 per 1000
(28 to 86)

RR 0.89
(0.5 to 1.57)

1215
(4 studies)

⊕⊕⊕⊝
moderate1,3,4,5,6

Progression to AIDS
Follow‐up: median 48 weeks

32 per 1000

42 per 1000
(17 to 106)

RR 1.32
(0.53 to 3.3)

1215
(4 studies)

⊕⊕⊕⊝
moderate1,3,4,5,6

Discontinuation rate
Follow‐up: median 48 weeks

164 per 1000

154 per 1000
(118 to 200)

RR 0.94
(0.72 to 1.22)

1215
(4 studies)

⊕⊕⊕⊝
moderate1,3,4,5,6

All severe adverse events
Follow‐up: median 48 weeks

201 per 1000

203 per 1000
(121 to 342)

RR 1.01
(0.6 to 1.7)

1054
(4 studies)

⊕⊕⊕⊝
moderate1,3,4,5,6

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 3 of the 7 RCT studies were open‐label (Ayala, Manosuthi, Swaminathan), but studies were not downgraded based on this fact.
2 2 of the 7 RCT studies did not use the <50 copies/mL level for defining virological success (Ayala used <400 copies/mL and Sow did not report the level used).
3 1 RCT study (van den Berg) looked at multiple indirect comparisons. Also, only 2 out of 7 RCT studies were conducted in developed country settings (Sow, Swaminathan).
4 2 of the 7 RCT studies looked at treatment in patients with tuberculosis (Manosuthi, Swaminathan).
5 1 out of the 7 RCT studies were industry funded (van Leth), while 2 out of the 7 studies had funding sources that were unclear.
6 Number of events <300 and/or confidence intervals include potential harm and benefit.

Figures and Tables -
Summary of findings for the main comparison. Efavirenz 600mg versus Nevirapine 200mg twice daily for initial treatment of HIV infection in antiretroviral‐naive individuals
Summary of findings 2. Efavirenz 600mg versus Nevirapine 400mg once daily for initial treatment of HIV infection in antiretroviral‐naive individuals

Efavirenz 600mg versus Nevirapine 400mg once daily for initial treatment of HIV infection in antiretroviral‐naive individuals

Patient or population: patients with initial treatment of HIV infection in antiretroviral‐naive individuals
Settings: Multiple locations
Intervention: Efavirenz 600mg versus Nevirapine 400mg once daily

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Control

Efavirenz 600mg versus Nevirapine 400mg once daily

Virological success
Follow‐up: mean 48 weeks

687 per 1000

763 per 1000
(646 to 900)

RR 1.11
(0.94 to 1.31)

803
(3 studies)

⊕⊕⊕⊕
high1,2,3,4,5

Change in CD4 count
Follow‐up: median 48 weeks

The mean Change in CD4 count in the intervention groups was
8.74 higher
(7.6 lower to 25.08 higher)

687
(2 studies)

⊕⊕⊕⊕
high1,3,4,5

Mortality
Follow‐up: median 48 weeks

52 per 1000

21 per 1000
(9 to 49)

RR 0.41
(0.18 to 0.94)

878
(3 studies)

⊕⊕⊕⊝
moderate1,3,4,5,6

Progression to AIDS
Follow‐up: 48 weeks

32 per 1000

25 per 1000
(10 to 65)

RR 0.79
(0.3 to 2.04)

620
(1 study)

⊕⊕⊕⊝
moderate1,3,4,5,6

Discontinuation rate
Follow‐up: median 48 weeks

222 per 1000

329 per 1000
(255 to 422)

RR 1.48
(1.15 to 1.9)

674
(2 studies)

⊕⊕⊕⊝
moderate1,3,4,5,6

All severe adverse events
Follow‐up: median 48 weeks

163 per 1000

218 per 1000
(152 to 311)

RR 1.34
(0.93 to 1.91)

803
(3 studies)

⊕⊕⊕⊝
moderate1,3,4,5,6

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1 3 of the 7 RCT studies were open‐label (Ayala, Manosuthi, Swaminathan), but studies were not downgraded based on this fact.
2 2 of the 7 RCT studies did not use the <50 copies/mL level for defining virological success (Ayala used <400 copies/mL and Sow did not report the level used).
3 1 RCT study (van den Berg) looked at multiple indirect comparisons. Also, only 2 out of 7 RCT studies were conducted in developed country settings (Sow, Swaminathan).
4 2 of the 7 RCT studies looked at treatment in patients with tuberculosis (Manosuthi, Swaminathan).
5 1 out of the 7 RCT studies were industry funded (van Leth), while 2 out of the 7 studies had funding sources that were unclear.
6 Number of events <300 and/or confidence intervals include potential harm and benefit.

Figures and Tables -
Summary of findings 2. Efavirenz 600mg versus Nevirapine 400mg once daily for initial treatment of HIV infection in antiretroviral‐naive individuals
Comparison 1. Efavirenz 600mg versus Nevirapine 200mg twice daily

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Virological success Show forest plot

4

1200

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.95, 1.10]

2 Change in CD4 count Show forest plot

5

1285

Mean Difference (IV, Random, 95% CI)

0.00 [‐23.17, 19.18]

3 Mortality Show forest plot

4

1215

Risk Ratio (M‐H, Random, 95% CI)

0.89 [0.50, 1.57]

4 Progression to AIDS Show forest plot

4

1215

Risk Ratio (M‐H, Random, 95% CI)

1.32 [0.53, 3.30]

5 Discontinuation rate Show forest plot

4

1215

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.72, 1.22]

6 Severe adverse events:Rash Show forest plot

4

1227

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.41, 1.03]

7 Severe adverse events:CNS Show forest plot

3

999

Risk Ratio (M‐H, Random, 95% CI)

2.87 [0.64, 12.79]

8 Severe adverse events: GIT Show forest plot

3

999

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.33, 1.38]

9 Severe adverse events: Pyrexia Show forest plot

2

929

Risk Ratio (M‐H, Random, 95% CI)

0.36 [0.10, 1.36]

10 Severe adverse events: Raised transaminases Show forest plot

2

1015

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.37, 0.95]

11 Severe adverse events: Raised alkaline phosphatase Show forest plot

1

787

Risk Ratio (M‐H, Random, 95% CI)

0.58 [0.14, 2.41]

12 Severe adverse events: Raised Amylase Show forest plot

1

787

Risk Ratio (M‐H, Random, 95% CI)

1.12 [0.54, 2.32]

13 Severe adverse events: Raised Triglycerides Show forest plot

1

787

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.28, 3.32]

14 Severe adverse events: Neutropenia Show forest plot

2

929

Risk Ratio (M‐H, Random, 95% CI)

0.28 [0.11, 0.76]

15 All severe adverse events Show forest plot

4

1054

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.60, 1.70]

Figures and Tables -
Comparison 1. Efavirenz 600mg versus Nevirapine 200mg twice daily
Comparison 2. Efavirenz 600mg versus Nevirapine 400mg once daily

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Virological success Show forest plot

3

803

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.94, 1.31]

2 Change in CD4 count Show forest plot

2

687

Mean Difference (IV, Random, 95% CI)

8.74 [‐7.60, 25.08]

3 Mortality Show forest plot

3

878

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.18, 0.94]

4 Progression to AIDS Show forest plot

1

620

Risk Ratio (M‐H, Random, 95% CI)

0.79 [0.30, 2.04]

5 Discontinuation rate Show forest plot

2

674

Risk Ratio (M‐H, Random, 95% CI)

1.48 [1.15, 1.90]

6 Severe adverse events: Rash Show forest plot

2

684

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.45, 3.07]

7 Severe adverse events:CNS Show forest plot

2

684

Risk Ratio (M‐H, Random, 95% CI)

7.52 [1.14, 49.80]

8 Severe adverse events: GIT Show forest plot

2

684

Risk Ratio (M‐H, Random, 95% CI)

1.29 [0.49, 3.44]

9 Severe adverse events: Pyrexia Show forest plot

1

620

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.14, 4.90]

10 Severe adverse events: Raised transaminases Show forest plot

2

684

Risk Ratio (M‐H, Random, 95% CI)

0.42 [0.22, 0.81]

11 Severe adverse events: Raised alkaline phosphatase Show forest plot

1

620

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.14, 4.90]

12 Severe adverse events: Raised Amylase Show forest plot

2

684

Risk Ratio (M‐H, Random, 95% CI)

2.19 [0.78, 6.14]

13 Severe adverse events: Raised Triglycerides Show forest plot

2

684

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.32, 4.22]

14 Severe adverse events: Raised cholesterol Show forest plot

1

64

Risk Ratio (M‐H, Random, 95% CI)

6.03 [0.75, 48.78]

15 Severe adverse events: Neutropenia Show forest plot

1

620

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.30, 2.29]

16 All severe adverse events Show forest plot

3

803

Risk Ratio (M‐H, Random, 95% CI)

1.34 [0.93, 1.91]

Figures and Tables -
Comparison 2. Efavirenz 600mg versus Nevirapine 400mg once daily