PIH receives $3 million grant to develop model for treating XDR-TB and HIV

	Examining a chest x-ray in Peru.

For more than a decade, Partners In Health has pioneered successful, community-based treatment of multiple drug-resistant tuberculosis (MDR-TB) and AIDS and has helped overturn policies that had accepted these diseases as untreatable "death sentences" in poor countries. Now, with help from a $3 million grant from the Open Society Institute (OSI), PIH is taking on another epidemic that has been widely described as "incurable" and that threatens to reverse recent progress in combatting HIV/AIDS – extensively drug-resistant tuberculosis or XDR-TB.

At a March 14 press conference, billionaire financier, philanthropist and OSI founder George Soros joined PIH co-founders Paul Farmer and Jim Yong Kim to announce plans to develop, test, and disseminate a model for treatment of drug-resistant tuberculosis in areas with high rates of HIV infection and AIDS. OSI's $3 million donation to PIH and the Brigham and Women's Hospital will be used to jumpstart a project in Lesotho, right next door to the South African province of KwaZulu-Natal where a widely reported outbreak of XDR-TB killed 52 out of 53 HIV-infected patients.

The project will start in the capital city of Maseru. A small building near the country's largest hospital is being renovated to serve as an in-patient facility that will provide effective treatment and infection control to prevent transmission of XDR-TB to other HIV patients. Plans are also in the works to build up laboratory capacity so that drug-sensitivity testing can be done quickly and accurately in Lesotho, rather than relying on sending sputum samples to South Africa and waiting months for the results. Once that diagnostic infrastructure is in place, the goal is to move treatment rapidly out of the hospitals, out of Maseru and out into the communities and rural areas where patients live.

As Jim Kim pointed out, "We're actually working in rural areas right now in Lesotho. And we believe that this treatment does not require hospitals. In fact, you want to stay away from hospitals as much as possible and provide treatment on a community-based level [in order to reduce transmission within clinical facilities]. So it'll start in Maseru but we believe that we must offer it throughout the entire country."

Press reports have frequently characterized XDR-TB as a new and virtually untreatable disease. Farmer and Kim emphasized that it is neither. Farmer pointed out that the lethal Kwazulu-Natal outbreak proved not that the disease is "untreatable" but that it was "untreated." The patients who died were all infected with HIV and many were receiving antiretroviral therapy. But they were never treated for drug-resistant TB. They received only standard treatment for drug-sensitive TB. By the time test results confirmed that they had XDR-TB, all but one of the patients had died.

XDR-TB is defined as tuberculosis that is resistant to the two main first-line drugs (as is the more widespread MDR-TB) and at least three of the six classes of second-line drugs used to treat MDR-TB. PIH has been treating patients with MDR-TB successfully for more than a decade. Among those patients, a significant proportion proved to be resistant to three or more classes of second-line drugs as well.

Socios En Salud, PIH's partner organization in Peru, started treating an epidemic of MDR-TB in the slums of Lima in 1985. Although the term had not yet been coined, about 20 percent of the first group of patients treated by Socios En Salud would now be defined as suffering from XDR-TB. Among that first cohort of patients, SES achieved overall cure rates of more than 80 percent, including better than 65 percent among patients suffering from what would now be called XDR-TB.

Based on that experience, Farmer and Kim stated with confidence that XDR-TB is neither new nor untreatable.

What is new, what complicates treatment and makes recent outbreaks of XDR-TB a potentially catastrophic public health emergency, is the eruption of XDR-TB in southern Africa, where as much as 30 percent or more of the adult population are infected with HIV.

"The new twist is one that we predicted, and many others did as well," Farmer stated. "That is that when HIV and drug-resistant tuberculosis collide, there is going to be an even more urgent need to intervene effectively because HIV really speeds up the process and makes these epidemics faster and more lethal."

Nevertheless, Farmer insisted, "We have no doubt as clinicians – as people who have taken care of patients – that we can successfully treat highly drug-resistant TB among patients co-infected with HIV. We've done it in Peru and Haiti. The bulk of our experience is with HIV-negative patients. But among those who do have co-infection, we've had excellent results."

"What happens when you go from having a small minority of your patients co-infected with HIV to the majority?" he added. "That's going to be the big challenge. But clinically, case by case, I think we know what to do. And if we do it correctly, most of them will get better."

Treating XDR-TB effectively and preventing it from spreading rapidly in areas with high HIV prevelance depends on strengthening capacity in three main areas, Jim Kim explained:

• laboratories and diagnostics;
• infection control; and
• effective treatment protocols for people who need to take medications for both XDR-TB and HIV.

Improved diagnostics and laboratory capacity are needed so that XDR-TB cases can be identified rapidly and treatment with effective second-line drugs can start within days, not months.

"Using slower methods, it can take three months, which is obviously unacceptable in this kind of outbreak," explained Dr. Salmaan Keshavjee, a PIH doctor and tb expert who will play a leading role in the Lesotho project. "Our hope in working with partners and building lab capacity in Lesotho is to get it so that a rapid diagnosis can take place within a few days and then within three weeks we can have the final susceptibilities to make sure that patients are getting exactly the right treatment."

Effective infection control measures, such as separate wards and ventilation systems are essential to keep air-borne tb germs from spreading like wildfire in hospitals, clinics and other institutions, particularly among HIV patients and others with weakened immune systems. Transmission within medical facilities has proven to be one of the main engines for the spread of drug-resistant tuberculosis. The best protection against it, long practiced and advocated by PIH, is to get treatment out of hospitals and into the patients' homes and communities. This community-based approach has been a lynchpin of PIH's success in treating MDR-TB in Peru and HIV in Haiti and Rwanda. And it will undoubtedly be a defining feature of the model for treatment of HIV-TB co-infection developed in Lesotho.

As to the treatment protocols themselves, "there aren't that many therapeutic options really," Paul Farmer points out. "The medications that we have, people agree on what those medicines are and, by and large, on the dosing and duration of therapy."

What do need to be tested, documented and disseminated, Jim Kim explains, are guidelines for precisely how the few medications available for XDR-TB can be delivered most effectively for people infected with HIV.

"First, when we're dealing with second-line tuberculosis drugs that do have side effects," Kim said, "we really need to work out in a very clear fashion how to deliver those drugs along with antiretroviral medications. We will have to develop these treatment guidelines in the next couple of years.

"The vision," he concluded, "would be that we would quickly develop a working model in Lesotho. WHO [the World Health Organization] would be working hand-in-glove with us, and when the treatment guidelines are available they would be immediately distributed. Lesotho would become a center of innovation and excellence and would be used as a training site for other countries interested in developing similar kinds of programs."

[published March 2007]