Local action for global impact: Making shorter TB preventive  treatments more accessible for all

Tuberculosis is the leading cause of death among people living with HIV, who are 18 times more likely to develop active TB disease than people without HIV. Globally, TB killed 1.3 million individuals in 2022, including 167,000 HIV patients. TB preventive treatments are urgently needed since people living with HIV and household contacts of TB patients, particularly young children under 5, are more likely to get active TB.

TPT has been shown to be successful in preventing the onset of active tuberculosis, with an efficacy rate ranging from 60% to 90%. The World Health Organization’s End TB strategy aims to reduce global TB incidence by 80%, TB deaths by 90%, and to eliminate catastrophic costs for TB-affected households by 2030 — but the targets cannot be met without increasing the use of TPT.

Until recently, the standard for TPT consisted of a daily dose of an antibiotic called isoniazid — known as IPT, or isoniazid preventive therapy — typically taken for six, nine, 12, or 36 months. Due to the length of treatment and the high pill burden, it has had limited acceptance and low patient adherence since it was established nearly 60 years ago.

A shorter treatment regimen exists, known as 3HP — a fixed-dose combination therapy that combines two antibiotics, isoniazid and rifapentine, taken once a week for three months. But until relatively recently, it was only available from one supplier, Sanofi, at a cost of $72 per treatment course, and therefore was mainly used in the United States. “The challenge was it wasn't produced in sufficient quantities, and the price was substantially more than the other standard of care [IPT],” said Robert Matiru, director of programs at Unitaid. 

“Not even the donors supporting these low- and middle-income countries were willing to pay that much,” said Makaita Gombe, market access director at The Aurum Institute, a leading Africa-based global health organization, which leads IMPAACT4TB, a consortium working in collaboration with WHO and funded by Unitaid. 

Following a call for proposals from Unitaid to address the lack of safe, affordable, and accessible short-term TPT, IMPAACT4TB was launched in 2017. “I think the whole world had realized that we needed a way to prevent TB that was not as long as the regimen that was there at that time,” Gombe said.

Drug to drug interactions were a concern, and research was first needed on the safety of co-administering antiretrovirals, or ARVs, and TB preventive medications, including modifying the formulation to increase demand: fewer pills, easier pill packs, lower prices, and a single pack of pills in blisters for weekly dosing, Gombe said. 

In addition, Aurum, Unitaid, and IMPAACT4TB consortium member Clinton Health Access Initiative brokered a deal that allowed two generic manufacturers, Lupin Limited and Macleods Pharmaceuticals, to introduce formulations of rifapentine at competitive prices, lowering the price per patient course from $72 to $10. The consortium also worked with manufacturers to bring the treatment regimen down from an initial nine pills to a three-pill regimen, including the development of a monthlong regimen known as 1HP.

Shorter medication regimens significantly increase the likelihood that a patient will finish their term of TPT, resulting in better outcomes and more lives saved. “This shorter regimen is very fair to us because of the pill burden,” said Sibanda. “Patients can select to get one box of TPT course to take with their ARVs, eliminating the need to return to the clinic,” Gombe added.

The impacts of the initiative are not only being felt in lower-income countries. So far, more than 78 countries around the world have purchased 3HP at a lowered price of $10 per patient course. “To us, this is a testament of people who need the product actually being able to access it. And really, that's because of evidence generated for use in broad populations, innovations in service delivery, the different formulations, and the price,” Gombe said.