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The HIV virus is rapidly developing resistance to common antiretroviral drugs. In low- and middle-income countries (LMICs), 10 percent of patients starting antiretroviral therapy (ART) and 40 percent of patients restarting treatment are infected with drug-resistant strains. The leading contributor to drug resistance is failure to adhere to treatment—a problem that plagues nearly three-fourths of patients in LMICs. In low-resource settings, many patients only have access to older, more toxic drugs, and more than one third of clinics report stock outs of HIV medicines. If action is not taken to improve treatment for these patients, drug-resistant strains of HIV-1 could result in 300,000 new infections and 425,000 deaths over the next five years. Last week, the US Congress overwhelmingly approved the nearly 1000-page 21st Century Cures Act, a massive initiative that channels new funding into the US National Institutes of Health and alters the way the US Food and Drug Administration (FDA) regulates certain medicines and devices. While some advocates argue that it weakens the FDA’s regulatory review process, others have applauded the legislation for its potential impact on the development and approval of new antibiotics. One provision—the limited population approval pathway—would allow the FDA to approve antimicrobials and other drugs for serious or life-threatening infections based on smaller clinical trials, addressing the challenge of identifying an adequate number of clinical trial participants (i.e., patients who are infected with drug-resistant pathogens). Another component addresses the FDA’s approach to updating antimicrobial susceptibility interpretative criteria, which informs the development of diagnostics that help physicians prescribe the best antibiotics for a given infection. The provision enables the agency to rely on other organizations’ research and update its criteria accordingly, rather than reviewing the research in house—a time consuming and costly process. While the legislation will likely be signed into law by President Obama, it could take years to fully implement. Scientists have long known that the tuberculosis vaccine offers protection against a number of pathogens and even treats certain conditions (i.e., bladder cancer and asthma), and a recent study in Cell Reports may explain why. Studies in mice and humans revealed that the Bacillus Calmette-Guerin vaccine increased glycolysis—the process of breaking down glucose—in monocytes, a type of immune cell. The effect, which lasts long after vaccination, enhances monocytes’ immunological memory—their ability to remember pathogens they have previously encountered—improving their disease detection and response capabilities. These findings could help scientists devise new strategies for boosting the immune system or its response to certain diseases. The European Medicines Agency (EMA) released a statement last week indicating that patients treated with certain hepatitis C medicines may experience a resurgence of previously latent hepatitis B. The phenomenon applies to a new class of drugs known as direct-acting antivirals and includes Daklinza, Exviera, Harvoni, Olysio, Sovaldi, and Viekirax. While there have only been 30 reported cases, the EMA is recommending patients be tested for hepatitis B before starting treatment.

Scientists at University of California, San Francisco have identified several drugs that block the Zika virus from infecting brain cells. After determining the types of brain cells susceptible to Zika, the researchers screened more than 2,000 Food and Drug Administration–approved medicines for their ability to protect these cells from the virus. The project revealed that azithromycin, a commonly used antibiotic, could provide protection against Zika in laboratory-grown brain cells. Not only is azithromycin widely available, it is also safe for use in pregnant women, an important characteristic as Zika infection during pregnancy can impede fetal development and result in devastating birth defects. An existing drug for gastrointestinal disorders has shown promise in treating and potentially even curing HIV in monkeys. Existing treatment—antiretroviral therapy (ART)—suppresses HIV, making the virus nearly undetectable in the blood, however, adherence is critical as just a few weeks off of treatment can result in a resurgence of the virus. Due to the demands of adherence and the expensive and toxic nature of many of these medicines, only one third of patients in the United States manage to keep the virus at these undetectable levels. Now researchers may have found a “functional cure” for HIV. The drug—vedolizumab—is approved to treat ulcerative colitis and Crohn's disease in more than 50 countries. In preclinical trials, vedolizumab kept the virus at bay in monkeys for up to two years after cessation of treatment. The National Institutes of Health recently initiated human clinical trials in which people living with HIV and AIDS will receive infusions of vedolizumab every four weeks. After several months, patients will stop taking ART, and their HIV viral load will be closely monitored to determine if the same curative effect is seen in humans. An experimental vaccine against Middle East Respiratory Syndrome (MERS) has successfully combatted the virus in mouse models and offers new insights into the design of subunit vaccines. Vaccines prompt the immune system to develop antibodies that recognize and attack a specific pathogen. Different proteins on the surface of a virus can elicit the production of distinct antibodies that vary in their ability to mobilize a robust immune response. Rather than using the entire virus, subunit vaccines contain specific proteins found on the surface of the virus. Consequently, scientists are able to include only the proteins that elicit the strongest immune response. However, this approach exposes the immune system to certain parts of the virus (i.e., the underside of these surface proteins) that wouldn’t normally be visible, and this can distract the immune system, prompting it to produce ineffective antibodies. In developing a subunit vaccine against MERS, researchers at New York Blood Center overcame this challenge by masking the spot on the vaccine that was distracting the immune system. The slightly tweaked vaccine has proved to be much more effective in protecting mice from MERS. Not only does this finding offer promise for the MERS vaccine, but this technique could be used to increase the efficacy of other subunit vaccines.

It’s that time of year when Americans join together with family and friends and give thanks for the many things in life for which they are most grateful. In the spirit of the Thanksgiving holiday, GHTC asked our members and staff to share what they are most thankful for in global health. Here’s what they had to say: “I am thankful for all patients who take part in clinical trials so that the world will have more effective regimens to end TB, in all its forms.” Willo Brock, Senior Vice President of External Affairs, TB Alliance “I’m thankful there is increasing global interest in the development and production of vaccines for diseases of poverty, like hookworm, schistosomiasis, and Chagas.” Tara Bracken, Communications Associate, Sabin Vaccine Institute “I am thankful that 2016 was a turning point for women’s HIV prevention research—one that brought us hope for one day soon expanding women’s options with a long-acting vaginal ring. I am also grateful for the amazing partners who believe women’s health and empowerment matter!” Zeda Rosenberg, Founder and CEO, International Partnership for Microbicides “I’m thankful for the new generation of emerging R&D leaders who are both generating new knowledge and achieving global health impact.” Dr. Timothy Mastro, Chief Science Officer, FHI 360 “I’m thankful for sustained US government funding to fight emerging epidemics, like Ebola and Zika, through R&D and scientific advancement.” Lindsay Litwin, Jhpiego Innovations “I’m thankful that elimination of sleeping sickness is now a real possibility thanks to new tests being strategically implemented alongside new vector control technologies and improved treatment regimens.” Dr. Joseph Ndung’u, Head of Neglected Tropical Diseases Programme, FIND “I’m thankful that the six antimalarials MMV and partners have brought forward are saving young lives today!” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful for research that has shown promise for an effective six-month regimen to cure XDR-TB [extensively drug-resistant TB].” Rabita Aziz, Policy Research Coordinator, ISDA Global Health “I’m thankful for the inspirational dedication and continued participation of all HIV vaccine clinical trial volunteers. Without you, the important work of finding a safe and effective HIV vaccine would not be possible.” Dr. Fran Priddy, Chief Medical Officer, International AIDS Vaccine Initiative “I’m thankful for the over 200 members of Congress who have co-sponsored the Reach Act to accelerate efforts to end preventable deaths of mothers and children around the world.” Brandon Ball, Policy and Advocacy Officer, PATH "I'm thankful for low-cost interventions like chlorhexidine gel for umbilical cord care being made more accessible to Sub-Saharan Africa to reduce newborn mortality." Assumpta Nantume, Communications Associate/Global Health Corps Fellow, Global Health Council “I'm thankful a new generation of Middle Eastern scientists are advancing the development, production, and characterization of new vaccines to help endemic countries better respond to the threat of infectious diseases like MERS, schistosomiasis, and leishmaniasis.” Chris Bennett, Senior Program Officer, Sabin Vaccine Institute “I’m thankful for pioneering donors such as UNITAID for funding development of new hepatitis C tests for countries where fewer than 1 percent of people living with hepatitis C have been diagnosed.” Catharina Boehme, Chief Executive Officer, FIND “I’m thankful for scientists and researchers who devote their lives to important global infectious disease work to help people around the world and to protect Americans here at home and the funding the US government provides for such important work.” Karen Goraleski, Executive Director, American Society for Tropical Medicine and Hygiene “I’m thankful for the tremendous progress we’ve made in advancing child and maternal survival and excited for the prospect of saving the lives of more than 6 million mothers and children by 2030 if we work together to advance and scale-up 11 promising innovations.” Heather Ignatius, Multilateral, US, and Europe Policy & Advocacy Team Lead, PATH “I’m thankful for researchers across the globe whose efforts have, with unprecedented speed, deepened our scientific understanding of and advanced new tools to prevent, detect, and treat Zika.” Kat Kelley, Senior Program Assistant, GHTC “I'm thankful so many good dengue vaccine candidates are in development that could help curb the growing global dengue epidemic.” Tara Bracken, Communications Associate, Sabin Vaccine Institute "I'm thankful for increased awareness on global antibiotic resistance and WHO's new evidence-based Infection Prevention and Control Guidelines." Danielle Heiberg, Advocacy Manager, Global Health Council “I'm thankful for the lives of mothers and babies that have been saved, sustained, and supported by midwives across the globe.” Shannon Egan, Jhpiego Innovations “I’m thankful that malaria rapid tests have contributed to better malaria control, which in turn has helped fuel a massive decline in childhood mortality over the past decade—and that partners around the world are working together to find innovative new solutions for identifying non-malarial causes of fever. Diagnosis matters!” Dr. Iveth J. González, Head of Malaria and Acute Febrile Syndrome programme, FIND “I’m thankful for the support of MMV’s committed donors and partners that make our work to develop new antimalarials for vulnerable populations possible.” Andrea Lucard, Executive Vice President of External Relations, Medicines for Malaria Venture “I’m thankful to be a part of the #StartStayAIDSFree initiative which aims to end AIDS in children by 2020.” Catherine Connor, Senior Director of Public Policy and Advocacy, Elizabeth Glaser Pediatric AIDS Foundation “I’m thankful that members of both major US political parties have continued to demonstrate strong, bipartisan support for global health research and development and US efforts to save lives around the world.” Marissa Chmiola, Communications Officer, GHTC

Researchers at Massachusetts Institute of Technology and Harvard Medical School have designed a star-shaped pill that releases medicines over the course of two weeks. The long-acting pill has six arms that can be folded into a capsule. Once the capsule reaches the stomach, its outer layer is dissolved, causing the six arms to pop out. Due to its size, the expanded pill is able to remain in the stomach until its arms detach and are digested one by one. The research team used the antimalarial ivermectin to test this delivery system in pigs. The medicine was continually released for two weeks—an impressive feat as oral medicines rarely last longer than a day. Long-acting medicines can significantly improve adherence to complicated treatment regimens. The researchers are now using the platform to develop drugs for neuropsychiatric disorders, HIV and AIDS, diabetes, and epilepsy. Someday soon, one drop of blood and a USB stick could be all that’s required to determine a patient’s HIV viral load. The system uses an electronic chip to detect the virus and transform it into an electronic signal, which is then picked up by the USB, enabling users to access their results off by computer. The device was used to evaluate nearly 1,000 blood samples and proved to be accurate 95 percent of the time, providing results in 21 minutes on average. Current techniques to assess viral load take three days. Patients in remote areas often have to wait much longer because their samples must be transported to laboratories. The HIV virus can develop resistance to antiretroviral treatment, resulting in increasing levels of the virus in the blood. Patients could use this tool to regularly monitor their viral load, ensuring early detection of resistance. During infection, bacteria deploy minute molecules—siderophores—to steal iron from human cells. Microbes need iron to reproduce and interfering with this process could debilitate bacteria, preventing infection. Scientists have sought to develop vaccines that train the immune system to respond to the presence of siderophores; however, the molecules are too small to prompt an adequate immune response. Now, two independent groups of researchers have demonstrated that attaching siderophores to large proteins boosts the immune response. One team used siderophores from the strain of E. coli that causes urinary tract infections, while the other used the strain of Salmonella that causes food poisoning. Both teams vaccinated mice and then exposed them to the bacteria several weeks later. While neither vaccine provided complete protection, infections were much less severe in vaccinated mice. Mice that were vaccinated against E. coli had one-tenth the bacterial load in their urine and kidneys and less inflammation in their kidneys and bladders. The Salmonella-based vaccine triggered the production of antibodies against the siderophores, resulting in a bacterial load 20,000-fold fewer in vaccinated mice.