Treatment of Latent Tuberculosis in Resource-Limited Settings

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.