Dr. Salmaan Keshavjee directs the Program in Infectious Disease and Social Change in the Department of Global Health and Social Medicine at Harvard Medical School, where he is also Associate Professor of Global Health and Social Medicine and Associate Professor of Medicine. He is a senior tuberculosis specialist at the Boston-based non-profit Partners In Health and a clinician in the Division of Global Health Equity at Brigham and Women’s Hospital. Trained as a physician and anthropologist, he has more than a decade of experience in the implementation of tuberculosis treatment programs in Russia and Lesotho, as a clinical researcher, and a global tuberculosis policy analyst and expert.
Dr. Keshavjee wrote the following for Science Speaks’ Blueprint series, in which clinicians, researchers and advocates address the key elements they would like to see in the Global AIDS response blueprint that Secretary of State Hillary Clinton called at the 2012 International AIDS Conference in Washington.
Leading by example: Bold steps are needed to stop tuberculosis deaths among patients living with HIV
By Salmaan Keshavjee
It is hard to believe that tuberculosis has been treatable since the late 1940s and still remains the number one killer of people with HIV worldwide. In 2011, UNAIDS launched an aspirational strategy called “getting to zero,” which advocates reducing tuberculosis deaths among people living with HIV by half between 2011 and 2015. Presently, according to the Stop TB Partnership, more than 1,000 people infected with HIV die every day from tuberculosis. It is clear that our current approaches to addressing the global tuberculosis pandemic are inadequate. For people living with HIV, this means profound excess suffering and death. Thus, as we look to the future, any credible blueprint for the United States’ response to the HIV epidemic must include a bold strategy for addressing deaths from tuberculosis.
Why do so many people with HIV die from tuberculosis?
Sometimes the best of intentions have unintended consequences. In 1993, as the global HIV pandemic was growing, most notably in sub-Saharan Africa, policy leaders in the international health community embraced the DOTS (directly observed therapy, short-course) strategy to combat tuberculosis. The strategy was driven by the desire to reach the largest number of patients while keeping costs low. The cost imperative ignored important principles of treatment and transmission control that had been known for decades. For people infected with HIV—so many of whom die from tuberculosis—this strategy had substantial gaps. It relied on passive case finding—waiting for sick patients to appear at a health center before they could receive care. It embraced smear microscopy—an outdated diagnostic for tuberculosis that has low sensitivity, especially in children and patients with HIV—at the cost of other diagnostic modalities, including (at that time) chest x-ray and mycobacterial cell culture. It ignored the treatment of latent tuberculosis infection, which even at the time had clearly shown a mortality benefit for people exposed to tuberculosis. And most dangerously, it ignored the diagnosis and treatment of drug-resistant strains of tuberculosis, a situation which, when combined with HIV, leads to rapid mortality and death. While some of this has changed in recent years—there are now some better diagnostics, treatment of latent tuberculosis among people living with HIV is accepted, and the treatment of drug-resistant tuberculosis is considered by many to be good practice—the implementation of the standard of care in many parts of the world has lagged. In many countries, tuberculosis treatment remains underfunded and is not well integrated with the rest of the health system.
Moral leadership and a clear implementation strategy are needed
When PEPFAR began in 2003, it set a moral and human rights benchmark for other global health initiatives: that the standard of care for HIV treatment in rich and poor countries should be the same. Equally important, it tied this to active implementation, so that the outcome of interest—saving patient lives—became a primary focus. With small exceptions, this orientation has not been a driving force in global tuberculosis policy. The results speak for themselves. Thus, Secretary Clinton’s call for the Office of the Global AIDS Coordinator to create a blueprint for the future of the United States’ response to the HIV epidemic—to ensure that our response continues to be scientifically and morally robust—is a tremendous opportunity for our country to lead the way in the fight against tuberculosis.
How might this happen? The HIV and tuberculosis epidemics overlap in a lethal way. People with HIV are at high risk of active disease with tuberculosis, and tuberculosis itself up-regulates cellular surface proteins that increase the ability of HIV to infect cells. Clearly, progress towards an AIDS-Free Generation is impossible unless the fight against tuberculosis is prioritized. Moreover, providing the correct care for people co-infected with HIV and tuberculosis will not only save numerous lives, but, as was the case with the response to the HIV epidemic, it will set the standard of care for the rest of the almost nine million people that continue to suffer from tuberculosis each year, helping to prevent the more than 1.5 million annual deaths.
What would it look like? In June 2012, a group of scientists, practitioners, policy-makers and activists gathered in Cambridge, Massachusetts, to develop a framework for stemming the tide of tuberculosis. After analyzing available tools and strategies that have been used to halt the spread of tuberculosis in rich countries—approaches that have been shown, in large part, to work—the consensus was that while there remains critical research and development gaps in the areas of tuberculosis vaccine development, point-of-care diagnostics and new anti-tuberculosis medicines, zero tuberculosis deaths is a realizable goal. The document that emerged from this meeting, the zero tuberculosis deaths declaration, has been signed by more than 135 organizations and 300 individuals. It outlines clear recommendations for achieving zero tuberculosis deaths, which must be included in the United States’ strategy to combat HIV.
First, bold targets for reducing tuberculosis incidence and zero TB-HIV deaths must be prioritized in the blueprint. This has to be set as a primary measurable outcome. These targets should then be closely tied to an investment framework for TB-HIV integration activities that aggressively scales up access to the current standard of care for tuberculosis diagnostics, treatment and prevention—using mechanisms to bring down costs such as a pooled procurement strategy for tuberculosis drugs, diagnostic tests, and other consumables. These critical first steps—tied to greater civil society participation in the partnership framework and country operating plan processes—are essential to achieving an AIDS-Free Generation.
Second, known strategies for stopping the spread of tuberculosis have to be actively implemented:
- Any response has to include active case detection using symptom screening, chest x-rays and molecular tests. This means focusing on adult and child contacts of those already sick with tuberculosis, with special focus on the settings where tuberculosis is transmitted (e.g. home, workplace , hospitals, factories, and mines). Recent data from South Africa and Zambia has shown that household case finding can reduce tuberculosis by 22% in high HIV-prevalence urban and rural settings. It also means screening all people with HIV for tuberculosis at HIV clinics, and maternal child health centers, and general practitioner clinics. Although this sounds fairly straightforward, these basic steps are often not taken because they need to be coupled with effective operational strategies.
- The United States’ strategy must identify patients early, and rapidly initiate the correct regimen for either drug-susceptible or drug-resistant tuberculosis. This means ensuring that programs have access to appropriate diagnostic capacity: rapid DNA approaches to first line drug sensitivity coupled with mycobacterial culture for second-line drug sensitivity. Once diagnosed, patients need access to high-quality first- and/or second-line anti-tuberculosis drugs in programs that are capable of monitoring their progress, treating side effects, and supporting them to successfully complete treatment. This is more than just giving them medicines, but ensuring that patients co-infected with tuberculosis and HIV have enough nutrition. Both diseases cause severe wasting, leaving patients in a very vulnerable physical state, making food support an important part of treatment. When done properly, high cure rates (and markedly lower rates of mortality) can be achieved. This approach has been convincingly demonstrated in Ethiopia, Lesotho, South Africa, Rwanda, and a number of other settings.
- Preventive therapy must be provided for patients whose tuberculin skin tests are positive, indicating latent tuberculosis infection. This approach has been shown to save lives in a number of populations, including people living with HIV. Without preventive therapy, millions of people with latent tuberculosis infection will develop active disease and community-based transmission of tuberculosis will continue unabated.
Lastly, any effective strategy has to ensure that HIV advocates at the community level are educated about the threat of tuberculosis. Community engagement has been an essential component in the global scale-up of HIV treatment. It has been lacking for tuberculosis, even in many high-burden settings. Active support for groups advocating for the standard of care for tuberculosis treatment—as part of a comprehensive United States strategy—can change this, helping to generate community demand for the most efficacious treatment, and encouraging governments to commit the required resources.
The United States has shown visionary leadership in the area of HIV treatment and changed the lives of countless people for the better. It is time to take on tuberculosis with the same moral and pragmatic vigor. Setting the benchmark by preventing the deaths of co-infected patients is the ideal place to start.