Treating latent tuberculosis

In the developed world, once it is clearly established that there is no active disease, many doctors recommend a course of anti-tuberculosis drugs to try and get rid of the latent infection.

In some settings, preventive treatment or 'prophylaxis' is also given to people with HIV who live or work in situations where exposure to M. tuberculosis is common. Examples include healthcare workers, caregivers and household contacts of people with active tuberculosis, miners and prisoners.

A number of regimens can reduce the risk of developing active tuberculosis in people with HIV. These include:

  • A six-month course of isoniazid, a low-cost drug that can be taken at either 5mg/kg daily to a maximum of 300mg or 15 mg/kg twice weekly to a maximum of 900mg twice a week. Pyridoxine (vitamin B6) is given along with isoniazid to prevent liver toxicity and peripheral neuropathy. Although studies have demonstrated that a nine-month course is superior to six months, there are concerns about decreased adherence with a longer duration of therapy.
  • Continuous isoniazid for 36 months has proven superior in those with positive tuberculin skin tests to a six-month course of isoniazid in a high TB burden setting, probably because it provides a degree of protection against reinfection.1
  • A three- or four-month course of rifampicin (Rifadin / Rimactane), with or without isoniazid. Rifampicin and isoniazid are available in one tablet as Rifater, Riffing 150, Riffing 300 and Rimactane 300.
  • A two-month course of pyrazinamide and rifampicin. There have been reports of severe hepatic injury following this combination in HIV-negative patients. However, a recent study claimed that the risk was low in HIV-positive patients and that the difference between the two treatment regimens in terms of risk of liver toxicity was marginal.2
  • A six-month course of isoniazid and ethambutol has been found as effective as a 36-month course of isoniazid in people with HIV, most of whom were not receiving ART, with high adherence rates.3

Isoniazid regimens are by far the most common and widely used, particularly in patients on antiretroviral therapy, as there are interactions between rifampicin and certain antiretrovirals. However, rifampicin is the most potent anti-tuberculosis medication available so most programmes choose to reserve it for treatment of active disease to reduce the likelihood of resistance developing in a population. 

Although prophylaxis can eliminate latent tuberculosis infection, it does not prevent a new infection. Those in frequent contact with people with tuberculosis may need to repeat prophylaxis every few years.

Careful adherence to the treatment schedule is necessary to prevent the development of resistance. Prophylaxis should therefore only be given to patients who can be relied upon to take their medication correctly.

A South African cohort study among miners found that isoniazid prophylaxis for miners without a history of active TB reduced the number of new cases by just over 30% during a two-year follow-up period.4 Study participants did not receive antiretroviral therapy. Another observational study of a South African workplace population beginning ART found that mortality risk was halved in those who also received isoniazid prophylaxis.5

References

  1. Samandari T et al. Preliminary results of the Botswana Isoniazid Preventive Therapy (IPT) clinical trial (6 months vs 36 months). 40th Union World Lung Conference, Cancun, 2009
  2. Gordin FM et al. Hepatotoxicity of rifampin and pyrazinamide in the treatment of latent tuberculosis infection in HIV-infected persons: is it different than in HIV-uninfected persons? Clin Infect Dis 39: 561-565, 2004
  3. Swaminathan S et al. Efficacy of a 6-month vs a 36-month regimen for prevention of TB in HIV-infected persons in India: a randomized clinical trial. Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 103, 2010
  4. Grant AD et al. Effect of routine isoniazid preventive therapy on tuberculosis incidence among HIV-infected men in South Africa: a novel randomized incremental recruitment study. JAMA 293: 2719-2725, 2005
  5. Innes C et al. Effectiveness of isoniazid preventive therapy in reducing mortality in patients on ART. Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 102, 2010
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