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Early results from CREATE studies support wider use of Isoniazid Preventive Therapy to prevent TB among people living with HIV;

Study finds that IPT-associated health risks are minimal and IPT is linked to a decrease in TB mortality.

BALTIMORE – November 11, 2010 – Early results from a group of clinical trials in Africa and South America support wider use of a low-cost treatment to prevent the emergence of active TB in people living with HIV/AIDS. 

In a supplement published today in the journal AIDS, researchers affiliated with the Consortium to Respond Effectively to the AIDS/TB Epidemic (CREATE) note that isoniazid preventive therapy (IPT) –an antibiotic that is part of the routine treatment for active TB disease and prevents the emergence of active TB disease in HIV-infected people – produces minimal associated health risks when monitored monthly by trained nurses.  Globally, TB is the leading cause of death for people infected with HIV, and effective preventive therapies are essential to reduce TB-related morbidity and mortality.

Isoniazid is a common antibiotic that has been used in TB treatment since the late 1950s.  While isoniazid is not recommended to be used alone for the treatment of active TB disease, earlier studies have indicated that the risk of developing drug resistance is minimal when IPT is administered to people who are also latently infected with TB.  IPT is administered as a nine-month course of daily medication, and it effectively prevents active TB disease in a high percentage of patients who complete a full course of treatment. 

“This is exciting news for the global fight against TB and HIV,” said Dr. Richard Chaisson of Johns Hopkins University.  “We have positive signs that IPT provides a safe and effective way to prevent TB in people living with HIV. The final results of the three trials that we are conducting in South Africa, Zambia, and Brazil are not yet ready, but partial results from studies conducted by Thibela TB in South Africa and THRio in Brazil suggest that we are on the right path.” 

Dr. Chaisson serves as principal investigator of CREATE, a research program funded by the Bill & Melinda Gates Foundation that is studying the most effective ways to prevent, diagnose, and treat TB using currently available medicines and technologies.  CREATE was launched in 2004, and the consortium expects to conclude a series of clinical trials in Brazil, South Africa, and Zambia sometime in late 2011.
Both TB and HIV are prevalent among migrant workers who live and work in the gold mining industry in South Africa, and several of the research articles published in the AIDS supplement present data from a study of community-wide IPT in South African gold mines.  The research intervention was conducted by the Aurum Institute of Johannesburg, in collaboration with the London School of Hygiene & Tropical Medicine, between 2006 and 2010.

Among results released today, one of the articles found that mortality was lower among individuals receiving IPT in combination with antiretroviral therapy for HIV infection.  These results support the routine use of IPT in conjunction with ART.

The studies also determined that people who undergo IPT experience few adverse events.  Of the 24,221 participants in the clinical trial, only 130 experienced important side effects related to treatment.  Serious adverse events, like liver toxicity, were rare, and the study found that clinical criteria can be used to screen patients for serious toxicity risks and safely monitor patients while they are on IPT.

Another paper established that chest radiography, where available, can be a useful adjunct to symptom screening in ruling out active TB. The identification and exclusion of active TB cases is critical to ensuring the long-term effectiveness of IPT because active TB must be treated with a combination of antibiotics to prevent the development of drug-resistant TB strains.

While patient uptake to IPT was surprisingly high in the Thibela TB study, one of the studies found that healthcare workers serve as the primary barrier to widespread adoption of IPT for HIV-infected patients in the local clinic setting.  Lack of experience with IPT among physicians must be addressed with efforts to raise awareness of the treatment by local healthcare leaders. New South African government national guidelines on the use of IPT for HIV-infected individuals have been recently released in the hope that more healthcare providers will adopt the use of IPT for people living with HIV.

In a CREATE study conducted among 29 public health clinics in Rio de Janeiro Brazil, over 5,000 HIV-infected patients have had tuberculin skin tests placed; 94% have been read and 18% were positive. Eighty-three percent of those with positive skin tests have completed therapy to date and < 2% have had minor adverse effects. This study demonstrates that IPT can be incorporated successfully into existing public health clinics.