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Review
, 2015 (4), CD006150

Adjunctive Corticosteroids for Pneumocystis Jiroveci Pneumonia in Patients With HIV Infection

Affiliations
Review

Adjunctive Corticosteroids for Pneumocystis Jiroveci Pneumonia in Patients With HIV Infection

Hannah Ewald et al. Cochrane Database Syst Rev.

Abstract

Background: Pneumocystis jiroveci pneumonia (PCP) remains the most common opportunistic infection in patients infected with the human immunodeficiency virus (HIV). Among patients with HIV infection and PCP the mortality rate is 10% to 20% during the initial infection and this increases substantially with the need for mechanical ventilation. It has been suggested that corticosteroids adjunctive to standard treatment for PCP could prevent the need for mechanical ventilation and decrease mortality in these patients.

Objectives: To assess the effects of adjunctive corticosteroids on overall mortality and the need for mechanical ventilation in HIV-infected patients with PCP and substantial hypoxaemia (arterial oxygen partial pressure < 70 mmHg or alveolar-arterial gradient > 35 mmHg on room air).

Search methods: For the original review we searched The Cochrane Library (2004, Issue 4), MEDLINE (January 1980 to December 2004) and EMBASE (January 1985 to December 2004) without language restrictions. We further reviewed the reference lists from previously published overviews, searched UptoDate version 2005 and Clinical Evidence Concise (Issue 12, 2004), contacted experts in the field and searched the reference lists of identified publications for citations of additional relevant articles.In this update of our review, we searched the above-mentioned databases in September 2010 and April 2014 for trials published since our original review. We also searched for ongoing trials in ClinicalTrials.gov and the World Health Organization International Clinical Trial Registry Platform (ICTRP). We searched for conference abstracts via AEGIS.

Selection criteria: Randomised controlled trials that compared corticosteroids to placebo or usual care in HIV-infected patients with PCP in addition to baseline treatment with trimethoprim-sulfamethoxazole, pentamidine or dapsone-trimethoprim, and reported mortality data. We excluded trials in patients with no or mild hypoxaemia (arterial oxygen partial pressure > 70 mmHg or an alveolar-arterial gradient < 35 mmHg on room air) and trials with a follow-up of less than 30 days.

Data collection and analysis: Two teams of review authors independently evaluated the methodology and extracted data from each primary study. We pooled treatment effects across studies and calculated a weighted average risk ratio of overall mortality in the treatment and control groups using a random-effects model.In this update of our review, we used the GRADE methodology to assess evidence quality.

Main results: Of 2029 screened records, we included seven studies in the review and six in the meta-analysis. Risk of bias varied: the randomisation and allocation process was often not clearly described, five of seven studies were double-blind and there was almost no missing data. The quality of the evidence for mortality was high. Risk ratios for overall mortality for adjunctive corticosteroids were 0.56 (95% confidence interval (CI) 0.32 to 0.98) at one month and 0.59 (95% CI 0.41 to 0.85) at three to four months of follow-up. In adults, to prevent one death, numbers needed to treat are nine patients in a setting without highly active antiretroviral therapy (HAART) available, and 23 patients with HAART available. The three largest trials provided moderate quality data on the need for mechanical ventilation, with a risk ratio of 0.38 (95% CI 0.20 to 0.73) in favour of adjunctive corticosteroids. One study was conducted in infants, suggesting a risk ratio for death in hospital of 0.81 (95% CI 0.51 to 1.29; moderate quality evidence).

Authors' conclusions: The number and size of trials investigating adjunctive corticosteroids for HIV-infected patients with PCP is small, but the evidence from this review suggests a beneficial effect for adult patients with substantial hypoxaemia. There is insufficient evidence on the effect of adjunctive corticosteroids on survival in infants.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Figure 2
Figure 2
Funnel plot to evaluate the presence of publication bias in trials investigating adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in HIV‐infected patients. The funnel graph plots the log of the treatment odds ratio against the standard error (SE) of the log odds ratio (an indicator of sample size). Open circles represent trials included in the meta‐analysis. The line in the centre indicates the summary log odds ratio. In the absence of publication bias, the log odds ratio estimates from smaller trials are expected to be scattered above and below the summary estimate, producing a symmetric triangular or funnel shape. When smaller trials with larger log odds ratios are missing, the funnel plot appears asymmetric and may indicate the presence of publication bias. In our systematic review the funnel plot looks symmetric. The Egger test for publication bias was not statistically significant (P value = 0.91).
Figure 3
Figure 3
Forest plot of comparison: 1 Adjunctive corticosteroids versus no such treatment, outcome: 1.1 Death at 1 month; adults.
Figure 4
Figure 4
Forest plot of comparison: 1 Adjunctive corticosteroids versus no such treatment, outcome: 1.2 Death at 3 to 4 months; adults.
Figure 5
Figure 5
Forest plot of comparison: 1 Adjunctive corticosteroids versus no such treatment, outcome: 1.3 Death in hospital; children.
Figure 6
Figure 6
Forest plot of comparison: 1 Adjunctive corticosteroids versus no such treatment, outcome: 1.4 Need for mechanical ventilation at 1 month; adults.
Analysis 1.1
Analysis 1.1
Comparison 1 Adjunctive corticosteroids versus no such treatment, Outcome 1 Death at 1 month; adults.
Analysis 1.2
Analysis 1.2
Comparison 1 Adjunctive corticosteroids versus no such treatment, Outcome 2 Death at 3 to 4 months; adults.
Analysis 1.3
Analysis 1.3
Comparison 1 Adjunctive corticosteroids versus no such treatment, Outcome 3 Death in hospital; children.
Analysis 1.4
Analysis 1.4
Comparison 1 Adjunctive corticosteroids versus no such treatment, Outcome 4 Need for mechanical ventilation at 1 month; adults.
Analysis 1.5
Analysis 1.5
Comparison 1 Adjunctive corticosteroids versus no such treatment, Outcome 5 Sensitivity analysis: Death at 1 month; adults; loss to follow‐up = dead.
Analysis 1.6
Analysis 1.6
Comparison 1 Adjunctive corticosteroids versus no such treatment, Outcome 6 Sensitivity analysis: Death at 1 month; adults; without Clement 1989.
Analysis 1.7
Analysis 1.7
Comparison 1 Adjunctive corticosteroids versus no such treatment, Outcome 7 Sensitivity analysis: Death at 1 month; adults; concealed allocation only.
Analysis 1.8
Analysis 1.8
Comparison 1 Adjunctive corticosteroids versus no such treatment, Outcome 8 Sensitivity analysis: Death at 1 month; adults; blinding of patients and caregivers.
Analysis 1.9
Analysis 1.9
Comparison 1 Adjunctive corticosteroids versus no such treatment, Outcome 9 Sensitivity analysis: Death at 1 month; adults; trials not prematurely halted.

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