Breakthroughs Blog: HIV/AIDS

This Monday, May 18 was HIV Vaccine Awareness Day (HVAD), and GHTC members AVAC, the International AIDS Vaccine Initiative (IAVI), and the Bill & Melinda Gates Foundation convened leaders in the field to discuss the state of HIV and AIDS vaccine research and development (R&D). The discussion—which was hosted as both a briefing for congressional staffers and a dialogue among partners—included Dr. Gaudensia Mutua of the Kenya AIDS Vaccine Initiative, Dr. Yegor Voronin of the Global HIV Vaccine Enterprise, and Michelle Dees of IAVI. With worldwide investment in HIV and AIDS vaccine research on the decline since 2007 and some members of Congress calling for further cuts to US investment in this area, the discussion illustrated four key reasons why now is the time to ramp up—rather than scale down—investment in HIV and AIDS vaccine R&D. (1) We are closer than ever to developing an HIV and AIDS vaccine Despite the complexity and mutability of the HIV virus and the difficulty of producing a vaccine, there are currently thirty different HIV and AIDS vaccine candidates in the research pipeline. To ensure that the best candidates advance, strong investments are needed to support this diverse portfolio of vaccines. While most of these candidates are still being tested for safety and for evidence of an immune response, one candidate has already demonstrated partial efficacy. The evidence from that clinical trial has since been used to adjust the vaccine regimen, and the new regimen is currently being tested in another round of clinical trials. (2) We cannot eradicate HIV and AIDS without a vaccine While we have made immense progress in combatting HIV and AIDS with AIDS-related deaths falling by 35 percent since the peak in 2005, eradication will not be possible without a vaccine. For every one person who starts treatment, two more are infected, resulting in 2.1 million new infections and 1.5 million AIDS-related deaths each year. The stigma surrounding the disease continues to impede diagnosis and treatment efforts globally. While existing tools—from antiretroviral treatment to voluntary male circumcision—have had a major impact on reducing the spread of the disease, a vaccine is needed to completely protect against infection. (3) Investments in HIV and AIDS vaccine R&D are producing broader impacts on global health The HIV virus is highly mutable, and is constantly adapting to better fight the immune system. Consequently, many of the standard approaches to vaccine R&D have not proved fruitful. One of the most common types of vaccines—a live attenuated vaccine—involves the use of a weakened, but live version of the pathogen to stimulate the immune system to develop antibodies. The mutability of the virus has made this approach impossible and unsafe. Alternately, scientists often examine the immune response of a survivor to develop a vaccine that will imitate or enhance that process. As no one has ever rid their body of the HIV virus once infected, researchers started the search without a roadmap for what might work. While developing a vaccine that can defend against an ever-changing virus has been a major challenge for scientists, the search has led to invaluable insights into the immune system and progress in vaccinology writ large. Additionally, investments in strengthening HIV and AIDS vaccine R&D capacity in endemic countries have produced broader research and health benefits. For example, the Kenya AIDS Vaccine Institute (KAVI) in Nairobi, Kenya, was established primarily to gather data and conduct clinical trials. However, in addition to the 11 vaccine candidates it has tested in the past 14 years, the institute trained more than 1,500 people between 2010 and 2014. These trainees have been educated in everything from laboratory management and clinical practice to grant writing and vaccine literacy. Additionally, the KAVI facility has been used to test vaccines and drugs for other infectious diseases including Ebola, has helped provide trial participants access to treatment options they may otherwise not have received, and has played a role in combating the stigma of HIV and AIDS in the local community. (4) A vaccine for HIV and AIDS would have enormous financial benefits While the human impact of HIV and AIDS is more than enough reason to invest in vaccine R&D, the continued financial cost of treatment should also be noted. The President’s Emergency Plan for AIDS Relief, which reaches nearly 5 million people each year, spends US$338 per patient per year on HIV and AIDS treatment, and that’s down from an initial $1,100. A vaccine could prevent between 5.2 and 10.7 million new infections and could consequently save $46 to $95 billion over ten years—just in treatment costs. For more information, check out these key messages from AVAC or this video featuring researchers and clinicians across the HIV vaccine field.

Breakthrough ideas are like children—they start small, they need constant nurturing, they don’t always develop according to schedule, but they change lives forever. In honor of Mother’s Day, GHTC is highlighting the stories of five mothers who have given birth to scientific discoveries or bold ideas that have transformed global health. 1. Ruth Bishop (b. 1933), Discoverer of Rotavirus Ruth Bishop at work in her lab. Photo: Stepping Stone Pictures As a young bacteriologist working in the 1970s, Ruth Bishop was on a quest to find the root cause of diarrheal disease—the most common illness among children worldwide. After much research, Bishop concluded that the disease was likely not caused by a bacterial agent, but instead by a virus. To continue her search, Bishop teamed up with two colleagues at the University of Melbourne – virologist Ian Holmes and electron microscopist Brian Ruck. In 1973, using an electron microscope, the team uncovered a previously unidentified virus in the biopsy sample from an intestinal lining. Bishop and her team went on to confirm presence of the virus in other samples. Their published results elicited a global response and confirmation of the virus’s presence in samples around the globe. The virus identified by Bishop and her team would come to be named rotavirus for its wheel-like shape. Rotavirus is the leading cause of severe diarrhea in children worldwide and affects nearly every child in their first three years of life. Bishop and her team went on to develop a diagnostic test for the virus, and their continued research helped pave the way for the development of a rotavirus vaccine which was introduced more than three decades after their initial discovery. Today there are two rotavirus vaccines commercially available with additional candidates in the research pipeline. Gavi, the Vaccine Alliance estimates that by 2030, 2.4 million lives could be saved through rotavirus immunization. Bishop, who is the mother of one son and is now officially retired, has watched these vaccine developments with excitement. “Rotavirus will always be around,” she said, “but we can stop it from being a killer.” For more information on Ruth Bishop, check out this Science in Public article. 2. Rosalyn Sussman Yalow (1921-2011), Unlocked breakthrough diagnostic technique Rosalyn Yalow at Bronx Veterans Administration Hospital in October 1977. Photo: US Information Agency Rosalyn Sussman Yalow knew by the age of eight that she wanted to be a scientist. Despite living in a time when few scientific opportunities were available to women, Yalow remained undeterred in her pursuit. After completing her master’s degree and PhD in physics while working as an electrical engineer and college instructor, Yalow decided she wanted to be a full-time researcher. Unable to find a research position, Yalow decided to volunteer at a Columbia University radiological research laboratory. There she was introduced to the emerging field of radiotherapy. A few years later in 1950 while working at the Bronx Veterans Affairs Hospital, Yalow would meet and begin working with her lifelong research collaborator Solomon Berson. Together the two would develop radio-immunoassay, a technique that used radioactive isotopes as markers to trace and measure concentrations of hormones, viruses, enzymes, and other substances in the body. Their discovery of this technique revolutionized biological and medical research and made possible the development of diagnostic tests for infertility, hypothyroidism, and dwarfism; and screening tests for infectious diseases such as hepatitis and HIV and AIDS in blood donations. In 1977 Yalow became the second woman to earn a Nobel Prize in medicine. A mother of two children, Yalow advocated for the advancement of women in sciences. In her Nobel Prize banquet speech, she said of women, “We must believe in ourselves or no one else will believe in us; we must match our aspirations with the competence, courage, and determination to succeed, and we must feel a personal responsibility to ease the path for those who come afterward.” For more information on Rosalyn Sussman Yalow, check out her bio on the American Chemical Society website or her obituary that appeared in The New York Times. 3. Flossie Wong-Staal (b. 1947), Leading HIV and AIDS researcher Flossie Wong-Staal at the National Cancer Institute. Photo: National Cancer Institute/Bill Branson At the age of 18, Flossie Wong-Staal left Hong Kong to pursue her passion for biology in the United States. After completing her PhD in molecular biology in 1972, Wong-Staal moved to Bethesda, Maryland to study retroviruses with pioneering AIDS researcher Robert Gallo at the National Cancer Institute. Together they searched for the cause of AIDS, which was by then spreading in the United States. In 1983, Wong-Staal, Gallo and their team discovered HIV, the virus that causes AIDS. Two years later, Wong-Staal became the first scientist to clone and produce a genetic map of the virus, both of which were critical steps toward the development of blood tests for HIV. Wong-Stall continued her research on the HIV virus for over a decade, and today she help leads a biopharmaceutical company she co-founded which is working to develop improved drugs for Hepatitis C. Wong-Staal, who is the mother of two daughters, said of her interest in research, “For me, as for most researchers, the main motivation is simply the satisfaction of making discoveries, finding things out that no one knew before.” 4. Dorothy Hodgkin (1910-1994), Mapped the structure of penicillin Dorothy Hodgkin demonstrates the structure of vitamin B12 with a model. Photo: C&EN Archives Born in the early twentieth century, Dorothy Hodgkin was a trailblazer for women interested in the sciences. As a teenager, Hodgkin received as a birthday gift from her mother a book by Nobel Prize–winning physicist William Henry Bragg that discussed using X-rays to “see” the three-dimensional structure of molecules. This present would change the course of her life. Fascinated by the ideas presented in the book, Hodgkin would make the study of this field her life’s work. After graduating from college, Hodgkin found a position in an x-ray crystallography lab where she went to work studying the complex organic molecules that help a living organism function. The technique she used involved crystallizing the substance she was studying, shooting X-rays at it, and then studying the ways the X-rays refract off the structure in order to determine its shape. In 1946, after four years of studying the antibiotic penicillin using this technique, Hodgkin determined its structure, marking an important advancement which would help manufacturers create semisynthetic penicillin. Over the course of her career, Hodgkin also determined the structure of vitamin B12 and insulin. In 1964, she became the third woman to win the Nobel Prize in chemistry. A mother of three children and grandmother of three grandchildren, Hodgkin said of her career, “I was captured for life by chemistry and crystals.” For more information on Dorothy Hodgkin, check out her bio on the Chemical Heritage Foundation website or Nobel Prize website. 5. Margaret Sanger (1879-1966), Birth control pioneer Birth control pioneer Margaret Sanger. Photo: public domain Margaret Sanger devoted her life to expanding the availability of birth control and contraceptive options for women. Sanger’s devotion to this cause was born out of personal tragedy. At age 19, Sanger watched her mother—who gave birth to 11 children and suffered seven miscarriages—die of tuberculosis. Sanger believed that her mother’s repeated pregnancies had weakened her body’s ability to fight the disease. Wishing to build a different life for herself, Sanger became a nurse. Serving the people of New York’s Lower East Side, Sanger tended to the needs of impoverished women who lacked effective options to prevented unwanted pregnancies and often resorted to back-alley abortions in desperation. This experience deepened Sanger’s resolve that women needed access to safe and effective contraceptives so they could stay healthy, limit their family size as desired, and break the cycle of poverty. As a young mother of three children, Sanger switched her focus from nursing to advocating for the legalization of birth control and making it universally available to women. Although Sanger experienced several legal victories over the next three decades which expanded contraceptive access, she remained frustrated by the lack of birth control options available to women and dreamed of a contraceptive pill that would be as easy to take as a vitamin. To make that dream a reality, she recruited reproductive health researcher Gregory Pincus and raised the needed funding from heiress Katharine McCormick. This collaboration would lead to the development and introduction of the first oral contraceptive in 1960. Today Sanger’s vision of a world where all women have the ability to prevent or space their pregnancies remains only partially realized. Although more than 99 percent of American women have used a contraceptive method in their lifetime, an estimated 222 million women in developing countries want to limit or control the timing of their pregnancies but lack access to modern contraceptives. Said Sanger, “No woman can call herself free until she can choose consciously whether she will or will not be a mother.” For more information about Margaret Sanger, check out her bio at the National Women's History Museum website or PBS website.

The World Health Organization (WHO) released a statement last week calling for the publication of all data from clinical trials for drugs, vaccines, and medical devices. The pharmaceutical industry has made great strides in reporting the results of clinical trials since the establishment of the WHO International Clinical Trials Registry Platform. However, a report released in conjunction with the WHO statement demonstrates that negative or inconclusive clinical trial results often go unreported, and there is still a need to publish data from older clinical trials. The United States Centers for Disease Control and Prevention (US CDC) is partnering with the African Union to establish an African Centres for Disease Control and Prevention (African CDC) comprised of a Coordinating Center in Addis Ababa, Ethiopia—where the African Union is located—and five Regional Collaborating Centers across the continent. The purpose of the African CDC is to support and connect African ministries of health to monitor and respond to disease outbreaks. The US CDC will provide initial technical expertise and will sponsor ten African epidemiologists and two public health experts from the US CDC to staff the Coordinating Center and Regional Collaborating Centers. Dr. Jack Whitescarver, director of the Office of AIDS Research (OAR) at the National Institutes of Health (NIH), will step down in July after leading the Office for 15 years. Dr. Whitescarver first joined the NIH in 1977 and he was involved in the initial detection and monitoring of the HIV and AIDS epidemic in the United States. He was also a major player in the NIH’s HIV and AIDS outreach and education efforts, prior to the establishment of OAR in 1988. Under his leadership, OAR has supported both international and domestic research efforts, with a focus on HIV and AIDS in minority populations and in women and girls. The United States Patent and Trademark Office (USPTO) at the US Department of Commerce announced the winners of the 2015 Patents for Humanity program. The winners will be granted an expedited patent application, ex parte reexam, or ex parte appeal before USPTO. This year's winners include Sanofi—the manufacturer of a synthetic version of the antimalarial artemisinin—and Novartis, a pharmaceutical company that has discovered a class of compounds that show promise in fighting drug-sensitive and drug-resistant tuberculosis. Sanofi is partnering with GHTC members PATH and the Bill & Melinda Gates Foundation to produce synthetic artemisinin, while Novartis has provided TB Alliance—another member of the GHTC—with the compounds to continue the research and development of treatments for tuberculosis.

India is expected to add all of the drugs currently used in the government’s HIV and AIDS and tuberculosis (TB) control programs to its list of essential medicines within the next six months. These drugs are currently available for free in public clinics; many patients, however, prefer private clinics due to perceived discrepancies in quality of care. The list, which was last updated in 2011, sets price caps to ensure that treatments remain affordable—paramount in a nation where more than 70 percent of the population lives on less than US$2 per day. China’s investments in health-related research and development (R&D) are expected to surpass US funding by 2023. The government of China has invested $1.1 billion in drug development since 2011, due to a policy mandate requiring increased funding for life sciences, including the pharmaceutical industry. Meanwhile, US funding for global health R&D has declined or plateaued each year since 2009. China is currently the world’s biggest manufacturer of active pharmaceutical ingredients and is becoming a leading site for contract research organizations, which support preclinical and clinical research for major pharmaceutical companies. The World Health Organization (WHO) issued a guidance document last week regarding a leading medicine for hepatitis C. The new guidance will inform the design of bioequivalence studies, which determine whether a generic is comparable to a patented product. The drug, sofosbuvir, is patented by Gilead Sciences and can cost up to $1,000 per pill. Proof of bioequivalence will be critical for manufacturers aiming to produce a generic drug and ultimately seek WHO prequalification for their product. In her final speech as commissioner of the US Food and Drug Administration (FDA), Dr. Margaret Hamburg defended the agency’s rigorous drug approval process. “Innovation doesn’t matter if the product doesn’t work,” she noted, highlighting the risks of “unsafe and ineffective medical products.” Hamburg’s remarks come as the House of Representatives Energy and Commerce Committee is in the process of developing legislation—known as 21st Century Cures—that calls on the FDA to expedite the regulatory process using its “breakthrough therapy” designation. This designation, which ensures an accelerated review and increased guidance from the FDA, was granted to 31 drugs in 2014. The 21st Century Cures legislation would allow the FDA to review products based only on preliminary clinical trial data and would allow companies to hold off on long-term safety and efficacy trials until after the product was on the market.