Treatment of latent tuberculosis infection in HIV infected persons.

Treatment of latent tuberculosis infection in HIV infected persons.

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. The objective of the review was to determine the effectiveness of TB preventive therapy in reducing the risk of active tuberculosis and death in HIV-infected persons. 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). Akolo et al 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. They 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. 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. 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 isoniazid (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 isoniazid monotherapy versus placebo among individuals with a positive tuberculin skin test (RR 0.74, 95% CI 0.55 to 1.00) and with isoniazid 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). The authors conclude that 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.

One-third of the world’s population has latent tuberculosis (TB) infection meaning that they are infected but have no symptoms. Once you are infected with TB, you are infected for life. The lifetime risk of progressing to active disease is about 10% but this soars to 30% or more in people with HIV infection who have a 5-10% annual risk of developing active TB. Several trials have shown that HIV-negative people who take isoniazid (INH) daily for 6 to 12 months have a substantially reduced risk of active TB. Daily INH also reduces the risk of active TB in people living with HIV, particularly those whose immune systems are healthy enough, as evidenced by a positive skin test to TB, to benefit from INH’s help. This updated Cochrane review confirms previous findings but calls for more research to find out how long people need to take preventive therapy and the best drug or drugs to take, either before or after antiretroviral treatment has started. Nonetheless, there is no justification to wait. All people with HIV should be assessed for TB, particularly in high TB prevalence settings, and if latently infected with TB they should placed on INH or combination anti-TB drugs. The challenge is to determine whether their TB infection is latent or active.