Implementing Isoniazid Preventive Therapy

Following WHO guidelines, all patients living with HIV who are not currently on treatment for TB, who have never been given a course of isoniazid, and who have a negative tuberculosis symptom screen should be prescribed a course of IPT for a minimum of six months.

In its 2011 Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings, the WHO clearly recommends that a course of IPT should be provided to all HIV-infected patients who are not currently on treatment for TB and who have a negative symptom screen (adults who deny current fever, cough, night sweats, and weight loss; and children older than 12 months who have none of the following: poor weight gain, fever, current cough, or contact with a person with TB). There is some evidence (though WHO reports it to be of moderate quality) that a course of 36 months or longer in adults and adolescents offers greater long- term protection than a course of six months, so WHO makes a“strong” recommendation that the duration of IPT should be at least six months and a “conditional” recommendation for a 36-month course or longer “for people living with HIV in settings with high TB prevalence and transmission, as determined by the local context and national guidelines.” [p. 17]

The isoniazid dose for adults is 300 mg per day, while the pediatric dose is 10 mg/kg/day. Children should also receive pyridoxine (vitamin B6) 25 mg per day. No specific recommendation was made by WHO regarding pyridoxine supplementation in adults and adolescents who receive isoniazid, but because peripheral neuropathy is associated with both isoniazid and nucleoside reverse transcriptase inhibitors, pyridoxine (25-50 mg) is often prescribed with the hope that it will reduce the risk of peripheral neuropathy.

The guideline also recommends a six month course of isoniazid for all HIV-infected children, adolescents, and adults who successfully complete treatment for tuberculosis. In addition, children under five years of age (including infants less than one year old), who are household contacts of a person with TB and have no evidence of TB disease themselves, should receive six months of isoniazid, regardless of their HIV status.

The guideline made the following additional recommendations:

  1. A positive tuberculin skin test is not required to qualify for IPT in high TB burden countries. TST testing is logistically difficult to accomplish as it requires a return visit 48 to 72 hours following placement of the test and a skilled health care worker both to administer and interpret the test. Sites that have required a positive TST prior to initiating IPT have seen large numbers of potential beneficiaries of IPT being lost to follow-up prior to its being prescribed. However, when it is feasible to perform the test without the risk of losing the patient to follow-up (as in hospitalized patients), it can be used to identify those most likely to benefit from IPT.
  2. A chest radiograph is not needed to rule out TB disease in an adolescent or adult with a negative symptom screen.

Providing IPT to PLHIV does not increase the risk of developing isoniazid-resistant TB. This should not be a barrier to providing IPT.

Research to determine optimal time for initiating IPT in persons living with HIV and optimal duration of treatment is ongoing. This toolkit will be updated to reflect any changes in international recommendations.

Selected Resources

World Health Organization. WHO Guidelines for Intensified Tuberculosis Case Finding and Isoniazid Preventive Therapy for People Living with HIV in Resource-Constrained Settings. Geneva: World Health Organization; 2011.

This long awaited document should help overcome the resistance many countries have to implementing IPT, and lead to rapid scale-up. Key recommendations are noted above.

HIV & AIDS Treatment in Practice. Time for Clear and Simple Messages about Delivering Isoniazid Preventive Therapy [special online bulletin]. HATIP: 2007;98. http://www&46;aidsmap.com/Time-for-clear-and-simple-messages-about-delivering-isoniazid-preventive-therapy-IPT/page/1255906/. Published November 29, 2007. Accessed October 10, 2011.

An excellent HIV & AIDS Treatment in Practice review that highlights the rationale and urgent need for implementing IPT

Cain KP, McCarthy KD, Heilig CM, et al. An Algorithm for Tuberculosis Screening and Diagnosis in People with HIV. N Eng J Med. 2010; 362(8):707-716

A carefully conducted study that identifies operating characteristics (sensitivity, specificity , negative predictive value) of numerous symptom screening questions and combinations of questions and identifies those with the highest sensitivity and negative predictive value in a population of HIV-infected patients to use as a means of identifying candidates for IPT.