Treatment of Latent Tuberculosis in Resource-Limited Settings

July 2006; updated July 2007

Chapter Contents

Background

Access to HIV Test and Tuberculin Skin Test

References

Background

Countries with a high prevalence of tuberculosis (TB), including resource-limited countries, traditionally relied on the bacillus Calmette-Guérin (BCG) vaccination rather than treatment of latent TB infection (LTBI) to prevent active TB. Because of the rapidly increasing rates of both TB and HIV in many countries, and the negative impact of each infection on the other, some pilot projects and national programs in resource-limited settings are now providing treatment of LTBI for HIV-infected persons. (See chapter Latent Tuberculosis for a general discussion of latent TB, including treatment options and patient education.)

Several issues should be considered in the treatment of LTBI among HIV-infected patients in resource-limited settings, including the following:

• Access to HIV test and tuberculin skin test (TST)
• The effect of previous BCG vaccination on the TST
• The need for TST before treatment of LTBI
• Criteria for isoniazid (INH) use, including the ability to rule out active TB before INH use
• The duration of treatment and the effectiveness of INH in treating LTBI
• Lack of access to preventive therapy other than INH
• Access to HIV and TB interventions

In some settings, a TST is not a prerequisite for INH use; in these settings the term "INH preventive therapy" (IPT) is used, rather than treatment of LTBI. To distinguish INH preventive therapy from intermittent prophylactic treatment of malaria in pregnancy (also abbreviated IPT), the acronym TB-IPT is used commonly.

Access to HIV Test and Tuberculin Skin Test

Interventions for HIV/TB-coinfected persons can occur only if both infections are diagnosed. Many countries are gradually expanding access to voluntary HIV counseling and testing at low or no cost, using either laboratory-based tests or rapid tests applied in the field. However, importation and use of purified protein derivative (PPD) for TB skin testing have been infrequent in many countries. An adequate supply of PPD and training in skin testing are required for programs that use the TST to identify patients who will be offered INH.

Several studies performed in sub-Saharan Africa have documented that the TST is effective in diagnosing TB infection, even in populations where previous BCG vaccination rates approached 100%.

Obtaining PPD test materials, training staff, and implementing a TST program can be formidable barriers to providing preventive treatment for LTBI. Some countries with very high rates of LTBI in their populations have decided not to require TSTs, but to offer IPT to all HIV-infected persons who meet certain criteria, without the use of TB skin testing.

Treatment with Isoniazid

Criteria for INH treatment of HIV-infected persons with suspected LTBI (positive TST or those from a high-prevalence population) require exclusion of active TB or risk factors for adverse events. Reliance on a chest x-ray to rule out active TB is prohibitively expensive for many resource-limited settings, however, and observational studies have shown that clinical criteria are 95% sensitive in ruling out active TB. Persons with cough, night sweats, fever, weight loss, loss of appetite, and lymphadenopathy are not offered INH preventive therapy. Instead, persons with those symptoms are evaluated for active TB or other conditions that require treatment. Other exclusion criteria include recent treatment for TB, active TB requiring combination therapy, unsatisfactory commitment to adherence with treatment; and preexisting liver disease, preexisting peripheral neuropathy, or previous severe adverse reaction to INH.

Randomized trials in Haiti, Zambia, and Uganda have demonstrated that a 6-month course of INH reduced the risk of active TB among HIV-infected persons by 60% over 1-5 years of follow-up. In resource-limited settings, the usual course of treatment is 6 months of daily INH treatment taken by the patient without observation, but with monthly clinic visits and prescription refills. A minimum of 180 doses taken within 9 months, or 80% of the doses within 6 months, is considered a complete regimen. Often, pyridoxine 10-25 mg daily also is provided. In studies of HIV-negative persons, the benefit of INH lasts 2 years. Current guidelines do not recommend prolonging INH preventive therapy beyond 6 months or repeating IPT in subsequent years; these issues are under study.

INH is the only treatment for LTBI that is available in much of the world. Rifampin and rifabutin combinations are very expensive and are not used for treatment of LTBI in resource-limited settings. The combination of rifampin and pyrazinamide is toxic and is not recommended in either industrialized or resource-limited settings.

Treatment of HIV/TB-coinfected persons requires adequate supplies of HIV test kits, materials for tuberculin testing, INH, pyridoxine, a trained staff, a mechanism for promoting adherence, and a system of record keeping, along with the willingness of patients to participate. In Uganda, only a small proportion of HIV-infected persons who were offered tuberculin testing eventually took a 6-month course of INH. Use of IPT requires substantial resources and planning. Projects and countries using this approach to TB prevention will have to identify resources for all of these requirements.

References

• American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society of America. Treatment of Tuberculosis . Am J Respir Crit Care Med. 2003 Feb 15;167(4):603-62. Available online at ajrccm.atsjournals.org/cgi/content/full/167/4/603.
• Blumberg HM, Leonard MK, Jasmer RM. Update on the treatment of tuberculosis and latent tuberculosis infection . JAMA. 2005 Jun 8;293(22):2776-84.
• Bucher HC, Griffith LE, Guyatt GH, et al. Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of randomized controlled trials . AIDS. 1999 Mar 11;13(4):501-7.
• Centers for Disease Control and Prevention, American Thoracic Society. Update: adverse event data and revised American Thoracic Society/CDC recommendations against the use of rifampin and pyrazinamide for treatment of latent tuberculosis infection--United States, 2003 . MMWR Morb Mortal Wkly Rep. 2003 Aug 8;52(31):735-9.
• Leinhardt C, Fielding K, Sillah J, et al. Risk factors for tuberculosis infection in sub-Saharan Africa: a contact study in The Gambia . Am J Respir Crit Care Med. 2003 Aug 15;168(4):448-55.
• Quigley MA, Mwinga A, Hosp M, et al. Long-term effect of preventive therapy for tuberculosis in a cohort of HIV-infected Zambian adults . AIDS. 2001 Jan 26;15(2):215-22.
• U.S. Public Health Service, Infectious Diseases Society of America. Guidelines for preventing opportunistic infections among HIV-infected persons . MMWR Recomm Rep. 2002 Jun 14;51(RR08);1-46. Available online at aidsinfo.nih.gov/Guidelines/.