How Cures Can Fail: Lessons for HIV/AIDS from Tuberculosis and Malaria

Despite the availability of powerful tools today to prevent, treat, and cure tuberculosis (TB) and malaria, why do these diseases continue to claim millions of lives? A new�report released by amfAR, The Foundation for AIDS Research, titled�"How Cures Can Fail,"�explores the factors that have stymied worldwide efforts to eradicate TB and malaria, which have been around for thousands for years, and outlines the lessons that can be applied to the global response to HIV/AIDS. �
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"For decades we have made significant breakthroughs in the fight against HIV, including cutting-edge research that could lead to an eventual cure. But we must be very careful not to declare that the fight against AIDS has been won," said amfAR CEO Kevin Robert Frost. "With millions of people still suffering and dying from curable diseases like TB and malaria, it is important to note that cures are not panaceas and that a sustained commitment is imperative to truly eradicate these diseases -- and others such as HIV/AIDS -- in our lifetime."��
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The World Health Organization (WHO) estimates that about one-third of the world's population has TB, though in most people the disease remains latent and they are neither infectious nor symptomatic. In 2015, however, TB surpassed HIV to become the world's most deadly infectious disease, causing 1.5 million deaths.

Furthermore, approximately 1.2 million people with HIV are also co-infected with TB. Malaria also remains a serious public health problem, particularly in sub-Saharan Africa. The WHO reports that there were 212 million new cases of malaria and 429,000 deaths worldwide in 2015.
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According to the�report, the history of the two diseases points to how lack of diagnosis, drug resistance, and insufficient research & development combine to cause millions of new infections and deaths from TB and malaria each year.
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Diagnosis
In 2014, only 63 percent of active TB cases were diagnosed, leaving an estimated 3.6 million cases undetected and untreated. Estimates also show that only 10 percent of global malaria cases are detected by malaria surveillance systems.
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Current diagnostic tools are inadequate, hindering the efficiency with which TB and malaria cases are accurately diagnosed and treated in a timely manner, especially in low- and middle-income countries where the majority of the disease burden is concentrated.�

For instance, WHO guidelines for TB diagnosis recommend administering serial tests that require patients to return to health centers for multiple visits. However, the travel and opportunity costs borne by the patients produce financial and logistical barriers to accurate diagnosis and contribute to loss to follow-up.
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And while new technologies hold promise for improving diagnostic accuracy, these tools remain unaffordable for many countries and their implementation is hindered by lack of staff training. Stigma and discrimination also remain barriers to TB and malaria testing.
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Drug Resistance

Like HIV, the global burden of TB and malaria has been complicated by drug resistance, further hampering efforts to control the spread of disease and improve access to treatment. In the case of TB and malaria, drug resistance arises when people cannot adhere to the treatment regimen - which sometimes produces serious side effects -- for the required time.

According to the report, the emergence of drug-resistant TB and malaria can be attributed to inappropriate administration of drug regimens to patients with drug-resistant disease or providing drugs to patients with entirely different diseases, often as a result of misdiagnosis.

Research & Development

While the predictable emergence of drug resistance necessitates ongoing development of new treatments, the report states that research and development (R&D) aimed at producing more effective treatments for TB and malaria have experienced serious shortfalls in recent years.

Global spending on TB R&D is at its lowest since 2008 and has decreased for the past two years. Meanwhile, the development of more accurate rapid diagnostic tools for malaria is underfunded.

Furthermore, as "diseases of poverty," developing drugs for TB and malaria is less lucrative for biotechnology and pharmaceutical companies than developing treatments and technologies for diseases that are prevalent in higher-income countries.

Lessons for HIV

While HIV is fundamentally different from TB and malaria, important lessons can be learned to effectively change the trajectory of efforts to end the AIDS epidemic.

Among the recommendations in the report is a call for 1) increased support for implementation research to develop evidence-driven, patient-centered and cost-effective strategies to improve patient outcomes and ensure engagement along the care continuum; 2) increased funding for R&D aimed at developing new treatments and diagnostic technology, and 3) sustained political and financial commitment to HIV from donor governments, multilateral and philanthropic organizations and other stakeholders.

"What we gather from the history of TB and malaria is that the development of a cure is just one step in controlling the epidemic," said Greg Millett, amfAR vice president and director of public policy. "Even if a cure for HIV is developed, we must remain committed to continuing research, and it is imperative that the HIV response be sustained in order to build effective delivery systems to reach the millions of people worldwide who are living with HIV."