Scolaris Content Display Scolaris Content Display

Flow Diagrams
Figures and Tables -
Figure 1

Flow Diagrams

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.1 Individual nadir changes in HIV‐1 RNA level.
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Figure 4

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.1 Individual nadir changes in HIV‐1 RNA level.

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.2 Changes in HIV‐1 RNA level on day 10.
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Figure 5

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.2 Changes in HIV‐1 RNA level on day 10.

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.3 Changes in HIV‐1 RNA level on day 22.
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Figure 6

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.3 Changes in HIV‐1 RNA level on day 22.

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.4 Antiviral response.
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Figure 7

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.4 Antiviral response.

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.5 No. of subjects with ≦400 copies/mL HIV‐1 RNA.
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Figure 8

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.5 No. of subjects with ≦400 copies/mL HIV‐1 RNA.

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.6 Change in CD4 cell count on day 8.
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Figure 9

Forest plot of comparison: 1 PRO 140 VS placebo, outcome: 1.6 Change in CD4 cell count on day 8.

Comparison 1 PRO 140 VS placebo, Outcome 1 Individual nadir changes in HIV‐1 RNA level.
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Analysis 1.1

Comparison 1 PRO 140 VS placebo, Outcome 1 Individual nadir changes in HIV‐1 RNA level.

Comparison 1 PRO 140 VS placebo, Outcome 2 Changes in HIV‐1 RNA level on day 10.
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Analysis 1.2

Comparison 1 PRO 140 VS placebo, Outcome 2 Changes in HIV‐1 RNA level on day 10.

Comparison 1 PRO 140 VS placebo, Outcome 3 Changes in HIV‐1 RNA level on day 22.
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Analysis 1.3

Comparison 1 PRO 140 VS placebo, Outcome 3 Changes in HIV‐1 RNA level on day 22.

Comparison 1 PRO 140 VS placebo, Outcome 4 Antiviral response.
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Analysis 1.4

Comparison 1 PRO 140 VS placebo, Outcome 4 Antiviral response.

Comparison 1 PRO 140 VS placebo, Outcome 5 No. of subjects with ≦400 copies/mL HIV‐1 RNA.
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Analysis 1.5

Comparison 1 PRO 140 VS placebo, Outcome 5 No. of subjects with ≦400 copies/mL HIV‐1 RNA.

Comparison 1 PRO 140 VS placebo, Outcome 6 Change in CD4 cell count on day 8.
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Analysis 1.6

Comparison 1 PRO 140 VS placebo, Outcome 6 Change in CD4 cell count on day 8.

Summary of findings for the main comparison. PRO 140 compared to placebo for treatment in people with HIV infection

PRO 140 compared to placebo for treatment in people with HIV infection

Patient or population: patients with treatment in people with HIV infection
Settings:
Intervention: PRO 140
Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

placebo

PRO 140

Individual nadir changes in HIV‐1 RNA level ‐ 0.5mg/Kg

The mean individual nadir changes in hiv‐1 rna level ‐ 0.5mg/kg in the control groups was
‐0.39 log10 copies/mL

The mean Individual nadir changes in HIV‐1 RNA level ‐ 0.5mg/Kg in the intervention groups was
0.19 lower
(0.42 lower to 0.04 higher)

19
(1 study)

⊕⊝⊝⊝
very low1,2

Individual nadir changes in HIV‐1 RNA level ‐ 2mg/Kg

The mean individual nadir changes in hiv‐1 rna level ‐ 2mg/kg in the control groups was
‐0.39 log10 copies/mL

The mean Individual nadir changes in HIV‐1 RNA level ‐ 2mg/Kg in the intervention groups was
0.81 lower
(1.22 to 0.4 lower)

19
(1 study)

⊕⊝⊝⊝
very low1

Individual nadir changes in HIV‐1 RNA level ‐ 5mg/Kg

The mean individual nadir changes in hiv‐1 rna level ‐ 5mg/kg in the control groups was
‐0.39 log10 copies/mL

The mean Individual nadir changes in HIV‐1 RNA level ‐ 5mg/Kg in the intervention groups was
1.44 lower
(1.73 to 1.15 lower)

19
(1 study)

⊕⊝⊝⊝
very low1,2

Individual nadir changes in HIV‐1 RNA level ‐ 162 mg weekly

The mean individual nadir changes in hiv‐1 rna level ‐ 162 mg weekly in the control groups was
‐0.23 log10 copies/mL

The mean Individual nadir changes in HIV‐1 RNA level ‐ 162 mg weekly in the intervention groups was
0.76 lower
(1.14 to 0.38 lower)

21
(1 study)

⊕⊝⊝⊝
very low1,2

Individual nadir changes in HIV‐1 RNA level ‐ 324 mg biweekly

The mean individual nadir changes in hiv‐1 rna level ‐ 324 mg biweekly in the control groups was
‐0.23 log10 copies/mL

The mean Individual nadir changes in HIV‐1 RNA level ‐ 324 mg biweekly in the intervention groups was
1.14 lower
(1.67 to 0.61 lower)

22
(1 study)

⊕⊝⊝⊝
very low1,2

Individual nadir changes in HIV‐1 RNA level ‐ 324 mg weekly

The mean individual nadir changes in hiv‐1 rna level ‐ 324 mg weekly in the control groups was
‐0.23 log10 copies/mL

The mean Individual nadir changes in HIV‐1 RNA level ‐ 324 mg weekly in the intervention groups was
1.42 lower
(1.8 to 1.04 lower)

21
(1 study)

⊕⊝⊝⊝
very low1,2

*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;

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 Randomization:method not specified;Allocation concealment: unclear;Blinding: method not specified;
2 total number of events is less than 400

Figures and Tables -
Summary of findings for the main comparison. PRO 140 compared to placebo for treatment in people with HIV infection
Summary of findings 2. PRO 140 compared to placebo for treatment in people with HIV infection

PRO 140 compared to placebo for treatment in people with HIV infection

Patient or population: patients with treatment in people with HIV infection
Settings:
Intervention: PRO 140
Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

placebo

PRO 140

Antiviral response ‐ 0.5mg/Kg

Study population

OR 3
(0.11 to 83.36)

19
(1 study)

⊕⊝⊝⊝
very low1,2

0 per 1000

0 per 1000
(0 to 0)

Medium risk population

0 per 1000

0 per 1000
(0 to 0)

Antiviral response ‐ 2mg/Kg

Study population

OR 27.44
(1.25 to 601.57)

19
(1 study)

⊕⊝⊝⊝
very low1,2

0 per 1000

0 per 1000
(0 to 0)

Medium risk population

0 per 1000

0 per 1000
(0 to 0)

Antiviral response ‐ 5mg/Kg

Study population

OR 399
(7.18 to 22157.52)

19
(1 study)

⊕⊝⊝⊝
very low1,2

0 per 1000

0 per 1000
(0 to 0)

Medium risk population

0 per 1000

0 per 1000
(0 to 0)

Antiviral response ‐ 162 mg weekly

Study population

OR 24.82
(1.17 to 527.12)

21
(1 study)

⊕⊝⊝⊝
very low1,2

0 per 1000

0 per 1000
(0 to 0)

Medium risk population

0 per 1000

0 per 1000
(0 to 0)

Antiviral response ‐ 324 mg biweekly

Study population

OR 57
(2.59 to 1253.22)

22
(1 study)

⊕⊝⊝⊝
very low1,2

0 per 1000

0 per 1000
(0 to 0)

Medium risk population

0 per 1000

0 per 1000
(0 to 0)

Antiviral response ‐ 324 mg weekly

Study population

OR 147
(5.35 to 4037.48)

21
(1 study)

⊕⊝⊝⊝
very low1,2

0 per 1000

0 per 1000
(0 to 0)

Medium risk population

0 per 1000

0 per 1000
(0 to 0)

*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; OR: Odds 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 Randomization:method not specified;Allocation concealment: unclear;Blinding: method not specified;
2 total number of events is less than 300

Figures and Tables -
Summary of findings 2. PRO 140 compared to placebo for treatment in people with HIV infection
Comparison 1. PRO 140 VS placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Individual nadir changes in HIV‐1 RNA level Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 0.5mg/Kg

1

19

Mean Difference (IV, Fixed, 95% CI)

‐0.19 [‐0.42, 0.04]

1.2 2mg/Kg

1

19

Mean Difference (IV, Fixed, 95% CI)

‐0.81 [‐1.22, ‐0.40]

1.3 5mg/Kg

1

19

Mean Difference (IV, Fixed, 95% CI)

‐1.44 [‐1.73, ‐1.15]

1.4 162 mg weekly

1

21

Mean Difference (IV, Fixed, 95% CI)

‐0.76 [‐1.14, ‐0.38]

1.5 324 mg biweekly

1

22

Mean Difference (IV, Fixed, 95% CI)

‐1.14 [‐1.67, ‐0.61]

1.6 324 mg weekly

1

21

Mean Difference (IV, Fixed, 95% CI)

‐1.42 [‐1.80, ‐1.04]

2 Changes in HIV‐1 RNA level on day 10 Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 0.5mg/Kg

1

19

Mean Difference (IV, Fixed, 95% CI)

‐0.24 [‐0.61, 0.13]

2.2 2mg/Kg

1

19

Mean Difference (IV, Fixed, 95% CI)

‐0.91 [‐1.23, ‐0.59]

2.3 5mg/Kg

1

19

Mean Difference (IV, Fixed, 95% CI)

‐1.57 [‐1.91, ‐1.23]

3 Changes in HIV‐1 RNA level on day 22 Show forest plot

1

64

Mean Difference (IV, Fixed, 95% CI)

‐0.87 [‐1.08, ‐0.66]

3.1 162 mg weekly

1

21

Mean Difference (IV, Fixed, 95% CI)

‐0.6 [‐0.87, ‐0.33]

3.2 324 mg biweekly

1

22

Mean Difference (IV, Fixed, 95% CI)

‐1.05 [‐1.63, ‐0.47]

3.3 324 mg weekly

1

21

Mean Difference (IV, Fixed, 95% CI)

‐1.36 [‐1.76, ‐0.96]

4 Antiviral response Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 0.5mg/Kg

1

19

Odds Ratio (M‐H, Fixed, 95% CI)

3.0 [0.11, 83.36]

4.2 2mg/Kg

1

19

Odds Ratio (M‐H, Fixed, 95% CI)

27.44 [1.25, 601.57]

4.3 5mg/Kg

1

19

Odds Ratio (M‐H, Fixed, 95% CI)

399.0 [7.18, 22157.51]

4.4 162 mg weekly

1

21

Odds Ratio (M‐H, Fixed, 95% CI)

24.82 [1.17, 527.12]

4.5 324 mg biweekly

1

22

Odds Ratio (M‐H, Fixed, 95% CI)

57.00 [2.59, 1253.22]

4.6 324 mg weekly

1

21

Odds Ratio (M‐H, Fixed, 95% CI)

147.0 [5.35, 4037.48]

5 No. of subjects with ≦400 copies/mL HIV‐1 RNA Show forest plot

2

Odds Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 0.5mg/Kg

1

19

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5.2 2mg/Kg

1

19

Odds Ratio (M‐H, Fixed, 95% CI)

3.0 [0.11, 83.36]

5.3 5mg/Kg

1

19

Odds Ratio (M‐H, Fixed, 95% CI)

13.15 [0.60, 288.33]

5.4 162 mg weekly

1

21

Odds Ratio (M‐H, Fixed, 95% CI)

3.0 [0.11, 82.40]

5.5 324 mg biweekly

1

22

Odds Ratio (M‐H, Fixed, 95% CI)

5.0 [0.21, 117.21]

5.6 324 mg weekly

1

21

Odds Ratio (M‐H, Fixed, 95% CI)

51.0 [2.30, 1129.95]

6 Change in CD4 cell count on day 8 Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

6.1 0.5mg/Kg

1

19

Mean Difference (IV, Fixed, 95% CI)

‐25.0 [‐100.14, 50.14]

6.2 2mg/Kg

1

20

Mean Difference (IV, Fixed, 95% CI)

3.0 [‐100.64, 106.64]

6.3 5mg/Kg

1

20

Mean Difference (IV, Fixed, 95% CI)

110.0 [3.14, 216.86]

Figures and Tables -
Comparison 1. PRO 140 VS placebo