Breakthroughs Blog: HIV/AIDS

A new compound has successfully protected monkeys from HIV, according to a study published in Nature last week. The compound stimulates the production of claw-shaped proteins that are able to simultaneously block the two different parts of white blood cells—the CD4 and CCR5 binding sites—to which the HIV virus normally attaches. After scientists at the Scripps Research Institute “vaccinated” monkeys with the compound, they repeatedly tried and failed to infect the monkeys with large doses of varied HIV strains over the course of a year. The team will next test if they are able to slow the replication of virus and the progress of the diseases in monkeys infected with HIV, before starting human trials. Last week, the World Health Organization approved the ReEBOV Antigen Rapid Test for Ebola, which requires only a test tube and a piece of paper and can provide results in approximately 15 minutes. The test is simple to administer and interpret, with the lead developer explaining “a drop of blood is placed on the paper, and if two lines appear, then it’s positive for Ebola.” The use of blood, however, requires a ‘biosafety cabinet’ in the form of either a box or a tent that can protect health workers from the virus. The test also has specificity and sensitivity issues, only detecting 92% of cases and with approximately 15% of uninfected people testing positive for Ebola. CBS correspondent Bob Simon investigated ZMapp, an experimental drug for Ebola, as part of his final story for 60 minutes before his death last month. Prior to the current Ebola epidemic, ZMapp had only been tested on monkeys; however, last summer, it was used to treat seven patients, five of whom survived. The US National Institute of Allergy and Infectious Diseases commenced clinical trials for ZMapp in Liberia on Friday. ZMapp is created using tobacco plants, which are saturated with a gene that stimulates the production of Ebola-fighting antibodies. As the plant grows, increasing rates of antibodies are produced—a process Simon likened to “a Xerox machine for antibodies.” Secretary of State John Kerry testified before the House Foreign Affairs Committee last Wednesday on the US Department of State’s 2016 budget proposal. The Committee’s Ranking Member Eliot Engel (D-NY) emphasized the importance of global health “research, infrastructure, and personnel,” in preventing future epidemics such as the Ebola crisis in West Africa and expressed his dismay at “proposed cuts to global health programs dealing with tuberculosis [and] neglected tropical diseases.”

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. Newsweek took an in-depth look at the work of Sanaria, a small biotechnology organization striving to develop a vaccine to effectively eradicate malaria. Naturally-acquired immunity is common in malaria-endemic regions, however, it takes an estimated three years for children to develop even partial immunity. The team at Sanaria has produced a vaccine that is considered the safest and most effective vaccine to date, preventing malaria in 100 percent of participants in initial trials. The vaccine defends against Plasmodium falciparum, the parasite responsible for nearly all fatal cases of malaria. Despite the success of initial trials and accolades such as the 2014 Vaccine Industry Excellence Award for “Best Prophylactic Vaccine,” Sanaria struggles to get adequate coverage or funding to continue, let alone escalate, the development of the vaccine. A virulent new form of HIV has been reported in Cuba, leading to an accelerated transition from HIV to AIDS. The HIV virus must attach itself to certain 'receptors,' or proteins on the cell membrane, before entering the human cell. The virus has historically attached itself first to the protein CCR5, and after several years it develops the ability to attach to the CXCR4 protein, a development which often correlates to the transition to AIDS. The aggressive new strand is recombinant, a variant of the virus resulting from a combination of multiple strands of HIV. Researchers at the Ku Leuven’s Laboratory for Clinical and Epidemiological Virology have seen particularly high levels of both the virus and the RANTES molecule in patients. The RANTES molecule, a natural part of the human immune response, combats HIV by attaching to the CCR5 proteins, which prevents the virus’s ability to enter the cells, resulting in the virus adapting to attach to the CXCR4 proteins. Patients with the new, recombinant strand may develop AIDS within just three years of infection, before many are even diagnosed with HIV. Mother Jones examined the impact of climate change on the spread of infectious diseases, and the role that vaccines can play in mitigating that impact. Climate change, and in particular, extreme climate events, can not only weaken existing health systems, but higher temperatures and levels of rainfall are actually correlated to increased cases of certain diseases, such as rotavirus. As Alistair Woodward, an epidemiologist at the University of Auckland explained, “ensuring that people are vaccinated is a logical thing to do as part of managing the risks of a rapidly changing climate.”

In this regular feature on Breakthroughs, we highlight some of the most interesting reads in global health research from the past week. According to a recent study out of Oxford University, rapid evolution of the HIV virus is slowing the virus’s ability to cause AIDS. In this study of 2,000 women in South Africa and Botswana, researchers found that the HIV virus had evolved to adapt to a specific gene known as HLA-B*57, which provides some protective effect against HIV, slowing the progress to AIDS. As the virus has adapted to reduce this protective effect in individuals, the virus has also reduced its ability to replicate, making it less virulent over all. Last Thursday, the UN Secretary-General launched his synthesis report for the sustainable development goals. In this report, Secretary General Ban Ki-moon reaffirmed his support for the 17 goals and 160 targets proposed by the United Nations Open Working Group, despite concerns from some member states that the current list is too long. Of the 17 proposed goals, two contain targets related to the research and development of new technologies. Researchers are developing a powdered form of the measles vaccine which could make it easier and safer to deliver the vaccine to people in developing nations. The current FDA-approved measles vaccine is a live virus that has been freeze-dried into a powder, which requires reconstitution with water before being administered via syringe. The new vaccine under development is a powder that can be inhaled. This new formulation would eliminate the need for sterile water and needles, as well as cold-chain storage. A modified regimen of the HIV vaccine candidate RV144 was shown to be safe and capable of inducing a robust immune response in safety trials in South Africa. RV144—which was developed by the US and Thai military—showed early promise in clinical trials, but it was found to lose efficacy over time. This new regime is the same earlier RV144 vaccine regime with an added booster shot one year later. Further clinical trials of this new regime are set to begin in South Africa in early 2015.

In this guest post, Emily Donaldson—program coordinator at AVAC—and Tom Harmon—senior policy analyst at the International AIDS Vaccine Initiative (IAVI)—write about the state of HIV prevention research funding as the first-ever conference devoted solely to HIV prevention research and development (R&D) takes place in Cape Town, South Africa, this week. Progress toward new tools to prevent HIV infection—including vaccines, microbicides, the use of antiretroviral treatment as HIV prevention, pre-exposure prophylaxis (PrEP), and a host of other options—is being presented and discussed at the inaugural HIV Research for Prevention Conference (HIVR4P) in Cape Town this week. While much progress has been made over the last few years, a four percent decline in funding between 2012 and 2013 speaks to the uncertain nature of the global environment in which that research is taking place. Such cuts hinder the ability of the researchers in Cape Town and across the globe to continue their work and could delay progress toward efficacy trials and eventual rollout of new prevention options. Investment data for almost every technology being discussed in Cape Town can be found in HIV Prevention Research & Development Investment in 2013: In a changing global development, economic, and human rights landscape—the most recent annual report by the HIV Vaccines and Microbicides Resource Tracking Working Group. The data show that the US government continued to fund more than 70 percent of HIV prevention R&D efforts in 2013. The combination of recent funding cuts across all US government budgets and declines in European investment in HIV prevention R&D led to the overall decline in funding from the previous year. Relying on such a small number of very committed donors is problematic when one or more of those donors is forced to reduce their support.The report also highlights funding declines in nearly every category of HIV prevention R&D, underscoring an urgent need to sustain and diversify funding sources through partnerships between governments, philanthropies, and the biopharmaceutical industry. The 2013 data provoke a concern that HIV prevention R&D is increasingly becoming a lower priority for public agencies funding international development, as portfolios and priorities within those agencies shift. Global health and development negotiations such as those around developing successors to the United Nations’ Millennium Development Goals take place far from the context of most HIV prevention clinical trials, but such international commitment at the highest levels can keep HIV and AIDS a priority for development agencies that can bolster support for science, technology, and innovation in endemic countries to end the epidemic. The report also compiles the number of volunteers taking part in HIV prevention R&D trials, which totaled almost 670,000 people in 2013. Most of these individuals are based in sub-Saharan Africa where the epidemic has its most profound impact and where several large-scale treatment-as-prevention and voluntary medical male circumcision trials and projects are underway. However, that balance doesn’t cut across all new prevention technologies—80 percent of volunteers in vaccine and PrEP trials reside in the United States and Europe. Ensuring that new HIV prevention options are appropriate and acceptable means testing them in partnership with those regions and those communities that need them most. Such communities are represented here at HIVR4P, and we’re excited by the opportunity to see them mingling with the experts working tirelessly to improve the state of HIV prevention R&D science and in turn hasten an end to the AIDS epidemic. However, they can’t do it without a diverse, committed investment base. Funding data show signals of vulnerability in support for HIV prevention R&D and support the need for policymakers and advocates to ensure that the state of the field remains a healthy one. The HIV Vaccines and Microbicides Resource Tracking Working Group consists of AVAC, IAVI, and the Joint United Nations Programme on HIV and AIDS. The report and summary materials are available at www.hivresourcetracking.org.