Treatment of latent tuberculosis infection in HIV infected persons

Abstract

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

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

Search strategy: We searched the Cochrane Controlled Trials Register (CCTR), MEDLINE, EMBASE, AIDSLINE, AIDSTRIALS and AIDSDRUGS. We also scanned reference lists of articles and contacted authors and other researchers in the field.

Selection criteria: We included studies in which HIV positive individuals were randomly allocated to preventive therapy for TB and 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: Two reviewers independently applied study selection criteria, assessed study quality and extracted data. Effects were assessed using relative risk for dichotomous data and weighted mean difference for continuous data.

Main results: 11 trials were included with a total of 8,130 randomized participants. Preventive therapy (any anti-TB drug) versus placebo was associated with a lower incidence of active tuberculosis (RR 0.64, 95% CI 0.51 to 0.81). 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 0.83, 95% CI 0.58 to 1.18.). Limited data suggest that the initial protective effect against tuberculosis may decline over the short to medium term. 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. Overall, there was no evidence that preventive therapy versus placebo reduced all-cause mortality (RR 0.95, 95% CI 0.85 to 1.06), although a favourable trend was found in people with a positive tuberculin test (RR 0.80, 95% CI 0.63 to 1.02).

Reviewer's conclusions: Treatment of latent tuberculosis infection (LTBI) reduces the risk of active tuberculosis in HIV positive individuals with a positive tuberculin skin test. The choice of regimen will depend on factors such as 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 and the influence of level of immunocompromise on effectiveness are needed.