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Meta-Analysis
. 2010 Jan 20;2010(1):CD000171.
doi: 10.1002/14651858.CD000171.pub3.

Treatment of latent tuberculosis infection in HIV infected persons

Christopher Akolo  1 , Ifedayo Adetifa, Sasha Shepperd, Jimmy Volmink
Affiliations
Meta-Analysis

Treatment of latent tuberculosis infection in HIV infected persons

Christopher Akolo et al. Cochrane Database Syst Rev. .

Abstract

Background: Individuals with human immunodeficiency virus (HIV) infection are at an increased risk of developing active tuberculosis (TB). It is known that treatment of latent TB infection (LTBI), also referred to as TB preventive therapy or chemoprophylaxis, helps to prevent progression to active disease in HIV negative populations. However, the extent and magnitude of protection (if any) associated with preventive therapy in those infected with HIV should be quantified. This present study is an update of the original review.

Objectives: To determine the effectiveness of TB preventive therapy in reducing the risk of active tuberculosis and death in HIV-infected persons.

Search strategy: This review was updated using the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, AIDSLINE, AIDSTRIALS, AIDSearch, NLM Gateway and AIDSDRUGS (publication date from 01 July 2002 to 04 April 2008). We also scanned reference lists of articles and contacted authors and other researchers in the field in an attempt to identify additional studies that may be eligible for inclusion in this review.

Selection criteria: We included randomized controlled trials in which HIV positive individuals were randomly allocated to TB preventive therapy or placebo, or to alternative TB preventive therapy regimens. Participants could be tuberculin skin test positive or negative, but without active tuberculosis.

Data collection and analysis: Three reviewers independently applied the study selection criteria, assessed study quality and extracted data. Effects were assessed using relative risk for dichotomous data and mean differences for continuous data.

Main results: 12 trials were included with a total of 8578 randomized participants. TB preventive therapy (any anti-TB drug) versus placebo was associated with a lower incidence of active TB (RR 0.68, 95% CI 0.54 to 0.85). This benefit was more pronounced in individuals with a positive tuberculin skin test (RR 0.38, 95% CI 0.25 to 0.57) than in those who had a negative test (RR 0.89, 95% CI 0.64 to 1.24). Efficacy was similar for all regimens (regardless of drug type, frequency or duration of treatment). However, compared to INH monotherapy, short-course multi-drug regimens were much more likely to require discontinuation of treatment due to adverse effects. Although there was reduction in mortality with INH monotherapy versus placebo among individuals with a positive tuberculin skin test (RR 0.74, 95% CI 0.55 to 1.00) and with INH plus rifampicin versus placebo regardless of tuberculin skin test status (RR 0.69, 95% CI 0.50 to 0.95), overall, there was no evidence that TB preventive therapy versus placebo reduced all-cause mortality (RR 0.94, 95% CI 0.85 to 1.05).

Authors' conclusions: Treatment of latent tuberculosis infection reduces the risk of active TB in HIV positive individuals especially in those with a positive tuberculin skin test. The choice of regimen will depend on factors such as availability, cost, adverse effects, adherence and drug resistance. Future studies should assess these aspects. In addition, trials evaluating the long-term effects of anti-tuberculosis chemoprophylaxis, the optimal duration of TB preventive therapy, the influence of level of immunocompromise on effectiveness and combination of anti-tuberculosis chemoprophylaxis with antiretroviral therapy are needed.

PubMed Disclaimer

Conflict of interest statement

We certify that we have no affiliations with or involvement in any organization or entity with a direct financial interest in the subject matter of the review (e.g. employment, consultancy, stock ownership, honoraria, expert testimony).

Figures

1
1
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 Any TB drug vs placebo, Outcome 1 Incidence of active TB (confirmed, probable or possible).
1.2
1.2. Analysis
Comparison 1 Any TB drug vs placebo, Outcome 2 Incidence of confirmed TB.
1.3
1.3. Analysis
Comparison 1 Any TB drug vs placebo, Outcome 3 Incidence of death (all cause).
1.4
1.4. Analysis
Comparison 1 Any TB drug vs placebo, Outcome 4 Incidence of AIDS.
1.5
1.5. Analysis
Comparison 1 Any TB drug vs placebo, Outcome 5 Incidence of adverse events leading to stopping treatment.
1.9
1.9. Analysis
Comparison 1 Any TB drug vs placebo, Outcome 9 Mean time to AIDS.
2.1
2.1. Analysis
Comparison 2 Isoniazid vs placebo, Outcome 1 Incidence of active TB (confirmed, probable or possible).
2.2
2.2. Analysis
Comparison 2 Isoniazid vs placebo, Outcome 2 Incidence of confirmed TB.
2.3
2.3. Analysis
Comparison 2 Isoniazid vs placebo, Outcome 3 Incidence of death (all cause).
2.4
2.4. Analysis
Comparison 2 Isoniazid vs placebo, Outcome 4 Incidence of AIDS.
2.5
2.5. Analysis
Comparison 2 Isoniazid vs placebo, Outcome 5 Incidence of adverse events leading to stopping treatment.
2.9
2.9. Analysis
Comparison 2 Isoniazid vs placebo, Outcome 9 Mean time to AIDS.
3.1
3.1. Analysis
Comparison 3 Isoniazid + rifampicin vs placebo, Outcome 1 Incidence of active TB (confirmed, probable or possible).
3.2
3.2. Analysis
Comparison 3 Isoniazid + rifampicin vs placebo, Outcome 2 Incidence of confirmed TB.
3.3
3.3. Analysis
Comparison 3 Isoniazid + rifampicin vs placebo, Outcome 3 Incidence of death (all cause).
3.5
3.5. Analysis
Comparison 3 Isoniazid + rifampicin vs placebo, Outcome 5 Incidence of adverse events leading to stopping treatment.
4.1
4.1. Analysis
Comparison 4 Rifampicin + pyrazinimide vs placebo, Outcome 1 Incidence of active TB (confirmed, probable or possible).
4.2
4.2. Analysis
Comparison 4 Rifampicin + pyrazinimide vs placebo, Outcome 2 Incidence of confirmed TB.
4.3
4.3. Analysis
Comparison 4 Rifampicin + pyrazinimide vs placebo, Outcome 3 Incidence of death (all cause).
4.5
4.5. Analysis
Comparison 4 Rifampicin + pyrazinimide vs placebo, Outcome 5 Incidence of adverse events leading to stopping treatment.
5.1
5.1. Analysis
Comparison 5 Isoniazid + rifampicin + pyrazinamid vs placebo, Outcome 1 Incidence of active TB (confirmed, probable or possible).
5.3
5.3. Analysis
Comparison 5 Isoniazid + rifampicin + pyrazinamid vs placebo, Outcome 3 Incidence of death (all cause).
5.5
5.5. Analysis
Comparison 5 Isoniazid + rifampicin + pyrazinamid vs placebo, Outcome 5 Incidence of adverse events leading to stopping treatment.
6.1
6.1. Analysis
Comparison 6 Isoniazid vs rifampicin + pyrazinimide, Outcome 1 Incidence of active TB (confirmed, probable or possible).
6.2
6.2. Analysis
Comparison 6 Isoniazid vs rifampicin + pyrazinimide, Outcome 2 Incidence of confirmed TB.
6.3
6.3. Analysis
Comparison 6 Isoniazid vs rifampicin + pyrazinimide, Outcome 3 Incidence of death (all cause).
6.5
6.5. Analysis
Comparison 6 Isoniazid vs rifampicin + pyrazinimide, Outcome 5 Incidence of adverse events leading to stopping treatment.
7.1
7.1. Analysis
Comparison 7 Isoniazid vs isoniazid + rifampicin, Outcome 1 Incidence of active TB (confirmed, probable or possible).
7.2
7.2. Analysis
Comparison 7 Isoniazid vs isoniazid + rifampicin, Outcome 2 Incidence of confirmed TB.
7.3
7.3. Analysis
Comparison 7 Isoniazid vs isoniazid + rifampicin, Outcome 3 Incidence of death (all cause).
7.5
7.5. Analysis
Comparison 7 Isoniazid vs isoniazid + rifampicin, Outcome 5 Incidence of adverse events leading to stopping treatment.
8.1
8.1. Analysis
Comparison 8 Isoniazid + rifampicine vs Rifampicin + Pyrazinimide, Outcome 1 Incidence of active TB (confirmed, probable or possible).
8.2
8.2. Analysis
Comparison 8 Isoniazid + rifampicine vs Rifampicin + Pyrazinimide, Outcome 2 Incidence of confirmed TB.
8.3
8.3. Analysis
Comparison 8 Isoniazid + rifampicine vs Rifampicin + Pyrazinimide, Outcome 3 Incidence of death (all cause).
8.5
8.5. Analysis
Comparison 8 Isoniazid + rifampicine vs Rifampicin + Pyrazinimide, Outcome 5 Incidence of adverse events leading to stopping treatment.
9.1
9.1. Analysis
Comparison 9 Isoniazid vs isoniazid + rifampicin + Pyrazinamide, Outcome 1 Incidence of active TB (confirmed, probable or possible).
9.3
9.3. Analysis
Comparison 9 Isoniazid vs isoniazid + rifampicin + Pyrazinamide, Outcome 3 Incidence of death (all cause).
9.5
9.5. Analysis
Comparison 9 Isoniazid vs isoniazid + rifampicin + Pyrazinamide, Outcome 5 Incidence of adverse events leading to stopping treatment.
10.1
10.1. Analysis
Comparison 10 Isoniazid + rifampicin vs isoniazid + rifampicin + Pyrazinamide, Outcome 1 Incidence of active TB (confirmed, probable or possible).
10.3
10.3. Analysis
Comparison 10 Isoniazid + rifampicin vs isoniazid + rifampicin + Pyrazinamide, Outcome 3 Incidence of death (all cause).
10.5
10.5. Analysis
Comparison 10 Isoniazid + rifampicin vs isoniazid + rifampicin + Pyrazinamide, Outcome 5 Incidence of adverse events leading to stopping treatment.
11.1
11.1. Analysis
Comparison 11 Isoniazid vs placebo (stratified by AIDS status at baseline), Outcome 1 Incidence of confirmed TB.
11.2
11.2. Analysis
Comparison 11 Isoniazid vs placebo (stratified by AIDS status at baseline), Outcome 2 Incidence of death (all cause).
12.1
12.1. Analysis
Comparison 12 Isoniazid vs rifampicin + pyrazinimide (stratified by AIDS status at baseline), Outcome 1 Incidence of confirmed TB.
12.2
12.2. Analysis
Comparison 12 Isoniazid vs rifampicin + pyrazinimide (stratified by AIDS status at baseline), Outcome 2 Incidence of death (all cause).
See this image and copyright information in PMC

Update of

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MeSH terms