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Better, shorter TB treatments are available. Why aren’t more people receiving them?

By guest contributors David Branigan, Madlen Nash, and Natalie Shure

Everyone, everywhere, has a human right to benefit from scientific progress. Attaining the ‘right to science’ is often a necessary precursor to attaining the more well-known ‘right to health.’ Such is the case with tuberculosis (TB).

Treatment for TB has been known for being unusually long (lasting up to two years for drug-resistant TB) and often toxic (with side effects such as permanent hearing loss). But, thanks to continued scientific research, discovery, and development, TB treatment is improving. As of 2022, it is possible to treat TB with better and shorter regimens than ever before: as little as one month (or once weekly) for TB prevention, four months for drug-susceptible TB, and six months for drug-resistant TB. TB activists co-founded the 1/4/6×24 Campaign to demand the universal implementation of these regimens around the world by the end of 2024. Urgent action on the part of governments, global health actors, funders, researchers, and product developers is needed to make that happen.

Compared to current standards of care across the world, these newer regimens are revolutionary: the “1” regimens shorten TB preventive treatment by at least 50%, while the “6” regimens shave up to 18 months off outdated courses of treatments—all while reducing serious side effects like liver failure, nerve damage, and hearing loss. This time saved on treatment equates to dramatic improvements for people taking the regimens and national TB programs alike. Even the “4” regimens, which cut treatment duration by one-third, would save an estimated 75.9 million months of treatment through 2030 if every eligible adult was switched tomorrow, according to modeling in our new 1/4/6×24 Campaign Report. That’s 6.3 million years that people would get back to spend with loved ones, pursue passions, and feel healthy without debilitating side effects.

Concerningly, though, our assessment shows that not nearly enough people living with and at risk of TB are getting these game-changing regimens. Between 2018 and 2022, the number of people who received TB preventive treatment only met half the global target, and just 16% of those who received TB preventive treatment in 2022 got a “1” regimen. In 2023, only an estimated 29% of people treated for drug-resistant TB received a “6” regimen. The World Health Organization is not yet tracking uptake of the “4” regimens, but our analysis suggests the regimens remain vastly underutilized.

Given that we know these regimens are more tolerable, just as effective, and shorter than those currently in use, then why are so few people actually getting them? Our report probed various obstacles and, encouragingly, found they were hardly insurmountable.

Take, for example, the “4” regimen for adults and adolescents: the 1/4/6×24 Campaign coalition zeroed in on two key barriers, cost and pill burden. While in recent years TB community advocacy has helped reduce the price of rifapentine, one of the core drugs of the four-month regimen, the new regimen at current prices costs cash-strapped TB programs around three times as much as the six-month standard of care. But this price differential doesn’t take into account the fact that shorter regimens also drive non-medical savings for people on treatment for things like transportation to clinics and lost wages, to the tune of an estimated $110 million per year in India, South Africa, and the Philippines alone. Moreover, taking nine daily pills with the shorter four-month regimen compared to four daily with the longer regimen may be a disadvantage for some, but will soon be remedied by new fixed-dose combination tablets which will hit the market this year. As demand increases for the four-month regimen—millions of people are potentially eligible for the regimen each year—prices are expected to significantly reduce. The barriers for the “4” for children with nonsevere TB are different. This regimen is shorter, cheaper, uses no new drugs, and has an equivalent daily pill burden to its longer counterpart. The challenge here is supporting countries to update their clinical algorithms and national policies to reflect the latest World Health Organization guidance.

Countries that have emerged as leaders in implementing these novel regimens can serve as models for others: Malawi tapped trusted community-based civil society organizations to support administration of “1” regimens to household contacts of people living with HIV. Azerbaijan has moved to get the “4” regimen for adults to high-risk individuals within the penitentiary system with plans to expand access to the general population. Kenya came out as a leader in implementing the “4” regimen for children by rapidly updating policies, piloting the regimen, and moving forward with country-wide scale-up. The Philippines, amid reforms to decentralize the healthcare system, quickly recognized the delivery of “6” regimens as a way to expand drug-resistant TB services at the primary care level. 

Achieving the goals of the 1/4/6×24 Campaign by the end of this year is still in reach, but only if powerful actors step up. To get everyone affected by TB the best available evidence-based treatments they deserve, we need all hands on deck. Country governments must significantly increase their TB investments to deliver access to better diagnostics and treatments. The World Health Organization must facilitate dialogue among country governments and other stakeholders to address barriers and identify enablers for scaling up the shorter four-month regimen for adults and adolescents—a method they successfully spearheaded for the six-month regimen for drug-resistant TB. The Global Fund to Fight AIDS, Tuberculosis and Malaria must cover necessary up-front costs of the four-month regimen and use its market-shaping power, with support from groups like Unitaid and MedAccess, to bring costs down further. Research funders must finance studies to fill research gaps for children and pregnant and lactating people. And the diagnostics company Cepheid must drop the prices of its rapid molecular TB tests to $5 each to support high-burden countries to close diagnostic gaps. Without also increasing access to accurate diagnosis and drug resistance testing, access to the shorter regimens will remain limited.

These are just a few of the things that will pave the way for expanding access to innovative new treatments. But attention also must be paid to structural barriers. The 1/4/6×24 Campaign was inspired by the legacy of the late Partners In Health cofounder Dr. Paul Farmer, who emphasized the so-called “5 S’s” necessary for a country to deliver high-quality healthcare: stuff (drugs and diagnostics), staff (health workers), space (clinics and hospitals), systems (state and health financing infrastructure), and support (psychosocial services and nutritional assistance to support people on TB treatment and their families). Winning 1/4/6×24 will do more than secure better treatments for people affected by TB – it will secure happier, healthier communities and set us on track to end TB for good.

All authors are part of the 1/4/6×24 Campaign, but have no financial or industry conflicts to disclose.

About the authors:

David Branigan is the TB Project Officer at Treatment Action Group (TAG) where he advances TAG’s advocacy to promote increased investment in TB research and improved access to TB tools.

Madlen Nash is a Program Manager at Johns Hopkins University where her work focuses on ensuring community engagement in tuberculosis research and catalyzing the translation of evidence into policy.

Natalie Shure is the Programmatic Communications Coordinator at Treatment Action Group (TAG).

Disclaimer: Views expressed by contributors are solely those of individual contributors, and not necessarily those of PLOS.

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