TB Prophylaxis in HIV-Infected Adults: Stick with the WHO Recommendations

Summary and Comment |
July 11, 2011

TB Prophylaxis in HIV-Infected Adults: Stick with the WHO Recommendations

  1. Salim S. Abdool Karim, MD, PhD

In an open-label clinical trial, taking isoniazid alone for 6 months was just as effective as taking it for longer or adding rifamycin.

  1. Salim S. Abdool Karim, MD, PhD

Isoniazid is effective in preventing tuberculosis (TB) and is currently recommended by the WHO (at a dose of 300 mg daily for 6 months) for all HIV-infected individuals who have a positive tuberculin skin test or are living in areas where skin testing is not feasible and the prevalence of latent TB exceeds 30%. Unfortunately, isoniazid prophylaxis is not widely used because of concerns about drug resistance, low adherence rates, and the potential for reinfection.

In this open-label, randomized trial, researchers evaluated the efficacy of three alternative TB prophylactic regimens relative to standard isoniazid therapy. A total of 1148 HIV-infected adults in South Africa who had a positive tuberculin skin test but were not yet on antiretroviral therapy were randomized to receive one of the following:

  • Rifapentine (900 mg) plus isoniazid (900 mg) once weekly for 12 weeks

  • Rifampin (600 mg) plus isoniazid (900 mg) twice weekly for 12 weeks

  • Isoniazid (300 mg) daily for the duration of the study (≤6 years; continuous isoniazid)

  • Isoniazid (300 mg) daily for 6 months (controls)

The overall incidence of TB was 1.9 cases per 100 person-years. The incidence of TB or death (a composite endpoint) did not differ significantly between any of the alternative-regimen groups and the control group: 3.1 per 100 person-years in the rifapentine–isoniazid group, 2.9 in the rifampin–isoniazid group, 2.7 in the continuous isoniazid group, and 3.6 in the control isoniazid group. The continuous isoniazid group (which received the drug daily for a median of 3.3 years) had the highest rates of serious adverse events and of both temporary and permanent treatment discontinuation.

Comment

These findings suggest that the alternative prophylactic treatments evaluated here achieve outcomes similar to those attained with the standard, WHO-recommended 6-month course of isoniazid treatment. No benefit is gained by taking isoniazid for more than 6 months or by adding rifampin or rifapentine. The current WHO-recommended regimen is as effective as (and cheaper than) longer isoniazid regimens or combination treatments.

Citation(s):

Reader Comments (1)

Dr Kewal Krishen Thassu

As weekly doses of Rifapentine and isoniazid have similar efficasy and lower side effects and at the same time it has better compliance level. WHO should reconsider its recommendation for prevention of tb. in HIV infected individuals in the light of current study .

Competing interests: None declared

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