BOSTON — For people with HIV, a daily 1-month tuberculosis (TB) prevention regimen provides the same protection as the standard 9-month regimen, according to results from a new study.
"This has the potential to become the standard of care," said Carl Dieffenbach, PhD, from the National Institutes of Health. "It's easier to take a pill for a month, the side effects are significantly less, and the outcome is equivalent. To me it is a game-changer."
The data come a little more than a week after the World Health Organization released updated guidelines supporting TB prophylaxis. Around the world, TB kills more people with HIV than anything else, including AIDS-defining illnesses. Although TB is less common in the United States than in other parts of the world, it is still an issue for people living with HIV and for those taking drugs for inflammatory diseases, such as rheumatoid arthritis and Crohn's disease.
A previous trial showed the effectiveness of a 3-month regimen, said Richard Chaisson, MD, from Johns Hopkins University in Baltimore, Maryland (JAMA Pediatr. 2015;169:247-255).
That study led his team to ask, "Can we do better?"
And that turned into a 1-month mouse model, which appeared to be successful, Dr Chaisson, who has been working on the prevention of TB for 3 decades, said here at the Conference on Retroviruses and Opportunistic Infections (CROI) 2018.
Understanding that a 1-month regimen "would be phenomenal," he and his colleagues assessed a cohort of people 13 years and older who were living with HIV with no evidence of TB infection.
From Mice to Men
The 3000 patients were randomized to one of three treatment regimens: rifapentine 450 mg plus isoniazid 300 mg daily for 1 month; rifapentine 600 mg plus isoniazid 300 mg daily for 1 month; or standard isoniazid treatment for 9 months.
The researchers then analyzed who adhered to the treatment plan, who acquired TB, and how safe the experimental treatment was compared with standard treatment.
It's a daunting trial design, Chaisson told Medscape Medical News. For one thing, he and his team jumped straight from animal models to phase 3 efficacy trials, because there is no intermediary marker for TB acquisition.
"If you're doing an HIV trial, you can do viral load, you can do CD4 counts. And not every HIV study has an end point of AIDS or death," he said. "But with TB, TB or death is the end point for TB prevention."
At the end of the 3-year follow-up period, 32 people in the 1-month groups and 33 in the 9-month standard-care group had acquired TB. So 1 month of daily treatment provided the same protection as 9 months did. What's more, drug-resistance levels were similar between treatment groups.
Overall, toxicity was lower in the 1-month groups than in the 9-month group. Specifically, fewer people in the 1-month groups than in the 9-month group experienced neurologic events (14 vs 30) and liver events (28 vs 42). However, twice as many people in the 1-month group experienced hematologic events.
But the hematologic adverse effects are usually anemia or a drop in white blood cells, both of which usually reverse themselves after treatment ends, said Constance Benson, MD, from the University of California, San Diego.
Rates of TB are twice as high in San Diego county as they are in the United States in general, so Benson said she often talks to patients about how to treat latent TB.
She pointed out that 6 or 9 months of isoniazid can contribute to peripheral neuropathy in people with HIV, something they often struggle with. So for her, these data are promising, and might surpass the 3-month regimen recommended by the Centers for Disease Control and Prevention.
"I always love something that's going to simplify therapy, so I think this is an important study," Benson said. "It gives us an option for people who are unlikely to stick with it. To be able to tell patients that you can take this for 1 month and reduce the risk of developing TB by 80% to 90% is great."
The completion rate in the 1-month groups was 97%, whereas studies of 6- to 9-month isoniazid have adherence rates of 60% to 70%, she noted, adding that, in the clinic, that rate is much lower.
More work needs to be done to replicate the findings and address any outstanding issues, said Dieffenbach. But if those issues can be addressed, he said he could see this becoming a reasonable regimen for people who live with or who have been in contact with people recently diagnosed with TB.
"As scientists and public health officials, we need to be cautious," he said. "This looks really good. But now let's figure out where this study may have had a soft underbelly, address that, and do a companion study to see how it does pass muster. But overall, it's a really great outcome to have at CROI.
The study drug was provided by Sanofi Pharmaceuticals. Chaisson has been a consultant for Otsuka, and his spouse holds stock in Merck. Dieffenbach has disclosed no relevant financial relationships.
Conference on Retroviruses and Opportunistic Infections (CROI) 2018: Abstract OA37LB. Presented March 5, 2018.
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Cite this: Fast-Acting Tuberculosis Prophylaxis in the Works - Medscape - Mar 06, 2018.