A new study implemented by the Aurum Institute and Perinatal HIV Research Unit (PHRU) in South Africa, the Ohio State University, Global One Health initiative in Ethiopia, and by Centro de Investigação de Saúde de Manhiça (CISM) in Mozambique has found that a single course of weekly rifapentine and isoniazid for three months (3HP) provides lasting protection against tuberculosis (TB).
According to the study, this course does not need to be repeated year after year. Other senior investigators were from the London School of Hygiene and Tropical Medicine and Johns Hopkins University Center for TB Research.
“We knew that 3HP was as effective as longer treatments for preventing TB disease in people with HIV, but there were doubts about the duration of protection in high-burden TB settings,” said Gavin Churchyard, group CEO of the Aurum Institute and principal investigator on the study. “What this study demonstrates conclusively is that there is no need to repeat a course of 3HP annually, a finding that has huge implications for health programs caring for millions of people with HIV globally.”
The clinical trial showed that repeat annual administration of 3HP did not provide additional benefits when compared to the single, three-month treatment course. The trial involved over 4,000 adults with HIV infection receiving antiretroviral therapy (ART) across three African countries.
The study was led by the Aurum Institute and sponsored by the KNCV Tuberculosis Foundation and funded by USAID through the Challenge TB project.
The study had two parts. The first part compared the effects of a single three-month course with two three-month courses given annually (for two years) to people living with HIV. The second arm compared 3HP to daily isoniazid for six months. Researchers enrolled 4,027 adults with HIV (and on ART) but without active TB and divided them into three groups: one group received 3HP for three months, another received 3HP for three months in year one and again in year two, and another received daily isoniazid for six months.
After two years of follow up, rates of TB were virtually the same in participants who received either one (three-month) course or two (three-month) courses of 3HP. The 3HP regimen was found to be safe, with similarly low rates of adverse effects in both 3HP arms of the trial.
After one year, the researchers found adherence to be higher among patients who were assigned to the 3HP groups than among patients who were prescribed six months of isoniazid. Completion of the treatment course in the combined 3HP arms (3610 people) versus isoniazid (404 people) arms was 90.4% versus 50.5%, respectively.
“When we’re asking people who are not sick to take medicines, adherence can be a huge problem,” said Professor Katherine Fielding, from London School of Hygiene & Tropical Medicine and senior statistician on the study. “This study confirms what we already suspected—that it’s easier for people to take pills once a week, for three months, than once a day for six months. Shorter regimens lead to higher adherence, which ultimately improves treatment outcomes.”
Tuberculosis, a disease that still kills around 1.5 million people every year, can lie dormant for decades before it strikes; this is called “latent TB infection.”
People with latent infection—almost a quarter of the globe—have no TB symptoms, are not contagious, and most of them don’t know they are infected. If left untreated, the latent infection can develop into active TB, the form of TB that makes people sick and is capable of being transmitted from one person to another.
“Latent TB infection is the breeding ground for the TB epidemic, and preventing new cases is critical if we want to end the TB epidemic,” added Churchyard.
People living with HIV are at high risk of developing TB and are 20 to 37 times more likely to move from latent infection to active TB. Treatment of TB infection is referred to as TB preventive therapy (TPT) and is one of the most powerful ways to prevent TB.
At the United Nations High-Level Meeting on Ending Tuberculosis in September 2018, heads of states committed to providing preventive treatment to at least 30 million people, including 6 million people living with HIV by 2022. That year, only 65 countries had reported initiating 1.8 million people living with HIV (PLHIV) and 349,487 children < 5 years on isoniazid preventive therapy (IPT).
“The fact that there is no need for a repeat dose of the medicines is good and timely news for all patients receiving 3HP as well as for public health practitioners,” said Dr Gidado Mustapha, director of Challenge TB and head of the project management unit at the KNCV Tuberculosis Foundation.
The 3HP regimen offers a shorter, safer alternative to the older standard of care (IPT) in which people take isoniazid every day for between six and 36 months.