One-month TB prophylaxis regimen equal to 9-month regimen in efficacy for HIV- infected patients

In persons with HIV, a 1-month course of daily rifapentine and isoniazid is as effective and safe in preventing active tuberculosis (TB) as the standard 9-month treatment regimen, according to results of a recent phase 3 clinical trial (ACTG 5279) presented at the 2018 Conference on Retroviruses and Opportunistic Infections.

Tuberculosis is the most common, serious, opportunistic infection in people infected with HIV worldwide, and an estimated 25% of the world’s population is infected with latent TB. According to data from the World Health Organization (WHO), TB caused 40% of all deaths in those living with HIV in 2016.

“Globally, tuberculosis kills more people than any other infectious disease, and it is the leading cause of death for people living with HIV,” said National Institute of Allergy and Infectious Diseases Director Anthony S. Fauci, MD. “These results have the potential to dramatically change clinical practice by offering people living with HIV who are at risk of developing active tuberculosis an additional, shorter-duration prevention option that is safe, effective, and more convenient. This study also will inform future research on prevention of tuberculosis disease among HIV-negative people at risk for developing active tuberculosis.”

Guidelines from WHO recommend TB prophylaxis with antibiotics in adults and adolescents infected with HIV who either test positive for latent TB or who have an unknown TB status but not active TB. The goal of this treatment is to stop active TB from developing in these persons.

The typical standard antibiotic regimens in many countries with endemic TB are lengthy 6- to 9-month courses of daily isoniazid.

For this study, researchers enrolled 3,000 people aged 13 and older from Botswana, Brazil, Haiti, Kenya, Malawi, Peru, South Africa, Thailand, the United States, and Zimbabwe who were infected with HIV. At baseline, approximately 50% of subjects were already being treated with antiretroviral therapy for their HIV.

Researchers randomized subjects to a 1-month course of rifapentine and isoniazid or a 9-month course of isoniazid and followed them for an average of 3 years.

The incidence of TB was less than expected and similar in both treatment arms: 32 subjects in the 1-month regimen and 33 in the 9-month arm developed active TB. Rates of TB were higher in subjects not being treated with antiretroviral therapy (ART) at baseline and in those with positive TB skin or blood tests.

Among subjects with low CD4+ cell counts at baseline, more of those receiving the 1-month treatment regimen developed active TB than those on the 9-month month regimen, but the difference was not statistically significant.

Researchers found that both regimens were safe, but fewer adverse events occurred with 1-month treatment. In addition, compliance was significantly better to the 1-month regimen compared with the 9-month regimen (97% vs 90%, respectively).

“Compared with standard tuberculosis preventive therapy for people living with HIV, this short-course therapy is similarly safe and effective but reduces treatment time from nine months to one,” concluded trial co-chair Richard E. Chaisson, MD, professor of medicine, epidemiology and international health, Johns Hopkins University, Baltimore, MD. “This ultra-short course therapy could become an important tool to control HIV-related tuberculosis and has the potential to transform global tuberculosis control efforts.”

This study was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and conducted by the NIAID-funded AIDS Clinical Trials Group.