November 15, 2010

Low-cost treatment helps prevent TB in people with HIV

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 tuberculosis in people living with HIV/AIDS.

In a supplement published Nov. 11 in the journal Aids, researchers affiliated with the Consortium to Respond Effectively to the AIDS/TB Epidemic, known as Create, note that isoniazid preventive therapy—using 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 isoniazid preventive therapy, or IPT, is administered to people who are 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 Richard Chaisson, a professor in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine. “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.”

Chaisson is principal investigator of Create, a research program funded by the Bill and 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 in late 2011.

Both TB and HIV are prevalent among migrant workers in the gold-mining industry in South Africa, and several of the articles published in the Aids supplement present data from a study of communitywide IPT in the mines there. The research intervention was conducted by the Aurum Institute of Johannesburg, in collaboration with the London School of Hygiene and Tropical Medicine, between 2006 and 2010.

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, such as 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 health care 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 health care leaders, the researchers said. New South African government national guidelines on the use of IPT for HIV-infected individuals have been recently released in the hope that more health care 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, more than 5,000 HIV-infected patients had tuberculin skin tests placed; of the 94 percent of the tests that were read, 18 percent were positive. Eighty-three percent of those with positive skin tests have completed therapy to date, and fewer than 2 percent have had minor adverse effects. The researchers said that this study demonstrates that IPT can be incorporated successfully into existing public health clinics.

For more on CREATE, go to tbhiv-create.org.