The 1/4/6x24 (one, four, six by 2024) campaign calls for TB patients to have access to evidence-based, long-awaited, shorter, less toxic treatment. But without mass availability of drugs, can India afford to adopt the protocol, ask experts.
Keyuri Bhanushali, a multi-drug resistant tuberculosis (MDR-TB) survivor, once lived her days in pain. First, she had to take daily injections. Her treatment regime stretched over 24 months, which meant quite a drain on her resources. She is now an advocate for the shorter duration therapy routines that reduce pain and speed up results. “TB treatment is costly. We should invest in these shorter duration treatments,” says Keyuri, who votes for the 1/4/6×24 (one, four, six by 2024) campaign, which calls on every eligible person with TB infection or disease to have access to evidence-based, shorter, less toxic TB treatment regimens. Currently, the shorter therapy protocols are not available in India.
“TB survivors are very excited to have shorter regimens for all forms of TB. However, these shorter treatments are futile until they reach the people who need them. Steps must be taken to make short-course regimens available to everyone eligible as a human right,” says Prof Madhukar Pai, Canada Research Chair in Epidemiology and Global Health and Associate Director, McGill International TB Centre. Experts worldwide, including Prof Pai, have argued for swifter implementation of short-course regimens as a human right in Nature Medicine (January 10).
The new campaign aims for the use of a one-month regimen (Isoniazide + Rifapentin) for latent TB infection (LTBI), a four-month regimen (Moxifloxacin+Rifapentin+Isoniazide+Pyrazinamide) for drug-sensitive TB (DSTB) and a six-month regimen (Bedaquiline+Pretomanid+Linezolid) for drug-resistant TB (DRTB).
The campaign’s name comes from its central demand that countries take action to implement the shortest available regimen – one month or once-weekly for TB prevention, four months for drug-sensitive TB and six months for drug-resistant TB – by the end of 2024. With investments in TB drug development and research, it is now possible to treat TB infection in as little as one month and most forms of drug-sensitive and drug-resistant TB in four and six months, respectively, says Lindsay Mckenna from the Treatment Action Group, USA.
One of the main problems with TB medicines is the length of treatment, which is a deterrent for many patients to complete the six–18 month course. As we look at elimination by 2030, a goal which has been set back by a decade (WHO) due to the recent pandemic, many strategies are being looked at. “Several trials are looking at newer and shorter regimens to ensure better compliance and thereby completion and cure,” says Dr Bornali Datta, Director. Department of Respiratory and Sleep Medicine, Medanta the Medicity, Gurgaon. As Project Lead of a Mission TB-Free Haryana, she adds that newer and shorter regimens for LTBI, DSTB and DRTB have been unequivocally proven to be non-inferior to current regimens in recent trials and can effectively replace the existing lengthier regimens, which are three months of Isoniazide+Rifampicin for LTBI, six-month regimen for DSTB (HRZE) and Bedaquiline-containing oral regimens which range from 9 to 18 months. Injectables have been removed from previous regimens for DRTB due to the unacceptable side effect of ototoxicity.This would be a significant breakthrough in achieving the goal of elimination, Dr Datta said.
“The campaign is ideal and it is great to see such activism around it. We should certainly push for it and there is no reason why it should not happen in India. However, despite evidence that supports the use of newer regimens, the availability of the newer drugs is a concern,” says Dr Lancelot Pinto, consultant pulmonologist and epidemiologist at P D Hinduja hospital, Mumbai. There has to be access to drugs like Rifapentin, Bedaquiline and Pretomanid, he argues. He also insists that the four-month regimen needs research as there may be Moxifloxacin resistance in the community. In India, according to Dr Datta, the BpaL regimen (Bedaquiline, Pretomanid and Linezolid) for drug-resistant TB has been approved but rollout is slow. The four month regimen for drug-sensitive TB is yet to be approved. Drug availability is still a concern for the one-month regimen for latent TB infection (LTBI). India wants to eliminate TB by 2025, five years ahead of the UN target. As per the National TB prevalence survey in India (2019-21) a little more than three people per 1000 had active TB cases.
“The costs of inaction are clear,” says Prof Pai. According to the Global Plan, failure to scale up the full range of available innovations would result in 6.6 million additional TB deaths and economic losses of $1 trillion by 2030. Steps must be taken to make short-course regimens available to everyone eligible as a human right. According to the World Health Organisation (WHO), the number of TB deaths increased for the first time since 2005 in 2020, wiping out more than a decade of progress in just 12 months. This trend continued in 2021, and estimated TB incidence also increased, reversing a long (if slow) decline in the number of people believed to develop TB each year.
Source: The Indian Express