PIH Experts on Game-Changing TB Drugs

Partners In Health tuberculosis experts are in the United Kingdom this week to discuss endTB, a project that is bringing delamanid and bedaquiline—the first new tuberculosis drugs developed in 50 years—to patients in 14 countries, where results so far have been revolutionary.

Tuberculosis is an airborne bacterial disease that can easily become resistant to antibiotics and kills 1.5 million people a year, surpassing HIV as the biggest infectious disease killer.

PIH is partnering with Médecins Sans Frontières, Interactive Research and Development, and UNITAID to tackle a form of TB that is resistant to standard drugs, referred to as multidrug-resistant tuberculosis. MDR-TB seems to have met its match against delamanid and bedaquiline. Each, in combination with other medications, is proving to be more effective and less toxic than current treatment.

PIH staff are presenting their findings for the first time to other clinicians, researchers, public health workers, and policymakers from over 125 countries at the annual Union World Conference on Lung Health in Liverpool.

Three of them—one based in Boston, one in Lesotho, and one in Kazakhstan—offered their thoughts on TB, the new drugs, and the significance of endTB.

Photo by Suzanne Camarata

Dr. Carole Mitnick began working in TB in 1996 when she joined PIH. She’s an associate professor at Harvard Medical School and a principal investigator of endTB’s clinical trial, which will test combinations of drugs in regimens containing delamanid or bedaquiline.

What day-to-day challenges are MDR-TB patients facing?

They are usually coping with years of illness. They've typically received multiple courses of treatment before getting treatment for MDR-TB. So they're facing tremendous social disruption from their families, partners, and employment. They're also facing huge financial challenges from having been sick for so long—either simply from not being able to work and earn a living, or because of the costs associated with TB treatment. And they're facing a desperate situation with treatment, which causes an enormous number of side effects, requires a daily painful injection that can cause abscesses, and much worse.

[Patients are] generally young, around 30 years old, who should be in productive periods of their lives with positive life events, like having children or developing long-term relationships. Instead, they’re facing two years of medications—often following several years of prior treatment.

How did endTB come together?

There's a long-standing partnership among PIH, MSF, and IRD that really goes back to working together on some global policy issues like the establishment of the Green Light Committee, which was one of the early mechanisms to make treatment for MDR-TB more available to people in resource-poor settings.

Some of that work extended to improving standards of measuring quality of treatment and making sure things often considered ancillary actually become a routine part of treatment—for example, social and economic support, addressing side effects, and additional tests that are required for MDR-TB treatment.

So with the conditional regulatory approval of the newest anti-TB drugs in 2012 to 2013, it was natural for these three groups to collaborate to expand access to the drugs in countries where they had a history of working. We agreed that the heterogeneity represented by patients and situations in these countries would provide important demonstrations for programmatic use of bedaquiline and delamanid for other countries in the world.

What do you hope to achieve at the conference?

Today we are holding an endTB symposium, which will be the first public presentation of the progress of the project. We're really excited to be able to present this. Over the last few years at this conference there has been a lot of discussion about planning for and preparing for the rollout of the new anti-TB drugs to the hundreds of thousands (maybe millions) who need them. But there's been very little reported progress other than in South Africa, which has been a lone pioneer with a high MDR-TB setting.

So we're pleased to talk about introducing the drugs in various settings—in Lesotho with a high rate of HIV co-infection; in Peru where there's been a lot of caution and uncertainty about these new drugs; and in Armenia and Georgia where there’s Hepatitis C co-infection and important prison populations.

We feel enthusiastic and privileged to be able to share this experience as a model for what a national TB program with these new drugs could look like.

 

Photo by Yerkebulan Algozhin / Partners In Health

Dr. Askar Yedilbayev, a lung specialist, is PIH’s program director for Russia and Kazakhstan.

PIH first began treating MDR-TB patients in Russia in the early 2000s. What has changed since then?

First of all, we changed doctors’ approach to treating patients. We realized that not only was treatment needed, but so was what we call ‘accompaniment.’ You can’t provide medicines and do nothing else. You need to provide food and psychosocial support to help patients adhere to treatment. We brought this comprehensive approach to the Ministry of Health, which resulted in a significant change in the national approach to MDR-TB, not only in Russia, but in neighboring countries, including Kazakhstan.

What are the challenges of the endTB project?

We haven't had these drugs before and realized more patients need them. It's so sad because there are people in other regions of the country where they don’t have the drugs because they’re simply not at endTB sites. It’s clear to me that in the countries of the former Soviet Union, like Russia and Kazakhstan, governments need to make these drugs available. I am happy that the endTB project serves as a catalyzer for this.

Another challenge is that because there are so many MDR-TB patients, we are treating the sickest. From a clinical standpoint, they are the hardest to cure. But we’re doing it.

What are the results so far?

We are collecting data and the first observations are very preliminary, but we already see improvements in patients. We have several who had been doing badly on regular drugs for MDR-TB and had had multiple treatments in the past, but with the new drugs they are responding to treatment very quickly. The drugs aren’t that toxic and patients aren’t suffering the same side effects they were before. For some, this is the first time in years they are responding to treatment. They were completely hopeless before. Without the endTB project, they would have died.

 

Photo by Rebecca E. Rollins / Partners In Health

Dr. Abera Leta is PIH’s country director in Lesotho. Before joining PIH, he managed TB control programs in Ethiopia for the World Health Organization.

PIH is treating hundreds of people with MDR-TB in Lesotho. To some, this amount may seem quite small. How significant is this prevalence rate?

When it comes to the burden of disease, some countries report a million cases per year. For example, China or India. But the ratio to the population is very small. When it comes to Lesotho, the incidence rate is 852 per 100,000 people in the population, which is one of the highest in the world.

This means we have many TB patients who are very sick and need diagnosis and medications. If we delay treatment, they may infect many more people who share the air they breathe—be it in a room, bus, wherever they are. TB is a public health problem. Every day counts.

What do you think of endTB?

This is definitely a landmark for the TB community and the world. We have been dealing with very old drugs, and we were treating MDR-TB with less effective, less safe drugs because we didn’t have alternatives. The two new drugs, bedaquiline and delamanid, are game-changing, and they’re our only options for improving management of MDR-TB.

What do you hope endTB will accomplish in Lesotho?

It is very important for us. We started MDR-TB treatment in 2007 in Lesotho, and we have enrolled thousands of patients, but we saw the outcome of standard drugs was not satisfactory. Most patients fail treatment or die. But these drugs are more effective and cause fewer side effects.

We have already enrolled about 55 patients, some of whom were failing treatment—they were on it for more than 24 months with no improvement, meaning they had no bacteriological conversion and were still infectious. But immediately after we put them on these new drugs, their sputum converted to negative. That means they are non-infectious. So you can see they are immediately improving.

What will happen once endTB is complete?

Since PIH is implementing the new drugs in collaboration with the National TB Program for Lesotho and jointly monitoring patient outcomes, we are hoping to make this part of the government’s national guidelines. Colleagues at the Program already appreciate what is going on now, including the significant improvement in outcomes of patients on these new drugs.