A published July 19 in the journal eLife brings new hope for HIV treatments. The research by scientists at the 91̽��, the Max Planck Institute for Dynamics and Self-Organization and the University of Cologne indicates that carefully designed cocktails of broadly neutralizing antibodies, or bNAbs, could help treat HIV while minimizing the risk of the virus evolving to “escape” treatment.

The study shows that computational approaches to selecting combinations of bNAbs based on viral genetics could help prevent viral escape, making HIV treatment more effective.

“Our study shows that leveraging genetic data can help us design more effective HIV therapies,” said senior author , a 91̽��assistant professor of physics. “Our approach may also be useful for designing therapies against other rapidly evolving agents that cause disease, such as the Hepatitis C virus, drug-resistant bacteria or cancer tumor cells.”

Antibodies are a class of proteins made by the immune system to recognize and fight pathogens. In HIV infections, bNAbs are a specific subset of antibodies that recognize multiple strains of HIV.

Broadly neutralizing antibodies offer a promising new tool to treat or potentially cure infections with rapidly evolving viruses such as HIV. But clinical trials using a single bNAb to treat HIV have shown that some viral strains may survive the treatment and lead to a rebound of viruses in the blood. Combinations of bNAbs may therefore be a more effective approach, but finding the best combinations is a challenge.

“For our study, we proposed using a computational approach to predict the effectiveness of bNAb combinations based on the HIV genetics,” said lead author Colin LaMont, a researcher at the Max Planck Institute for Dynamics and Self-Organization in Germany.

The team used high-throughput DNA sequencing to analyze the genomes of HIV viruses collected over 10 years from 11 untreated patients with HIV. They used these data to predict which viral strains might be able to escape treatment with different bNAbs and whether evolving to dodge bNAbs was associated with a survival cost. Next, using computational methods, they applied the knowledge gained to predict viral rebounds in three real-life trials using bNAbs. Finally, the team used their computational approach to develop a combination of bNAbs that is least likely to allow any virus to escape.

In the process, they discovered reasons why some bNAbs target broader populations of HIV than others. For example, some bNAbs, such as one called 10-1074, perform better against diverse populations of viruses because mutations that allow viruses to escape from 10-1074 also make those viruses less likely to survive. Others bNAbs, including one called PGT121, are more effective against viral populations with lower genetic diversity because mutations that enable escape are rare. Overall, the results suggested that the optimal combination includes three bNAbs: PG9, PGT151 and VRC01.

“We’ve shown the combination of PG9, PGT151 and VRC01 reduces the chance of viral rebound to less than 1%,” said LaMont. “It does this by targeting three different regions of the virus’ protective outer wrapping, or envelope.”

“Combining bNAbs, administered via intravenous infusion every few months, with current antiretroviral therapies that require daily doses could further improve long-term HIV treatment success,” said Nourmohammad.

Antiretroviral therapy reduces the ability of HIV to multiply and create new variants, limiting the genetic diversity of the viral population and lowering the likelihood for emergence of bNAb escape variants. The authors say that future studies are needed to confirm the potential benefits of combining antiretroviral therapy and broadly neutralizing antibodies.

Co-authors on the study are Jakub Otwinowski at the Max Planck Institute for Dynamics and Self-Organization and Kanika Vanshylla, Henning Gruell and Florian Klein at the University of Cologne in Germany. The research was funded by the National Science Foundation, the German Research Foundation and the Max Planck Institute for Dynamics and Self-Organization.

For more information, contact Nourmohammad at armita@uw.edu.

Adapted from a by eLife.

Using powerful tools and techniques developed in the field of , researchers at the 91̽�� and Scripps Research have new details about the human immunodeficiency virus, HIV. The findings bring into focus the basic architecture of the virus just above and below its surface and may help in the design and development of a vaccine that can protect against AIDS.

These detailed findings include 3D views of the structure and position of the virus’ envelope “spike” proteins (the protein, used when the virus binds with cells) in the context of the full virus. Normally, researchers view the protein particles separated from the virus or expressed as engineered or . In another key development, the scientists shed new light on the — the sugars on the proteins that can hide it from the body’s immune system.

“We’re looking at the whole virus particle and how this protein on the surface relates to the rest of the virus,” said lead author , associate professor of medicinal chemistry in the 91̽��School of Pharmacy. “And by looking at the intact virus structure, we can see how the different facets of this ‘face of the virus’ are being displayed and how they would be recognized by or hidden from the immune system.”

This intact view of the virus also allowed the scientists to gain new insights into positioning of the envelope spike protein on the surface relative to the internal protein structure, called the Gag lattice.

“This finding overturns previous models of how the parts of the viruses are assembled and helps to focus our attention on where the docking interaction of these two proteins is likely to be,” Lee said. “This interaction needs to be resolved in more detail, but at least the current work gives us the correct architectural model for the virus assembly.”

It was this particular finding that led to the title of the paper — “Cryo-ET of Env on intact HIV virions reveals structural variations and positioning on the Gag lattice” — ��. Another finding that had not been previously observed, the scientists pointed out, is that the “stalk” supporting the envelope proteins is flexible and can tilt, presenting both opportunity and challenges to the immune system’s neutralizing antibodies that protect cells from infection.

“Structural biology has driven HIV vaccine design, so as we get a better and better picture of what it is we’re targeting, that inspires innovation and may lead to improved vaccines,” said co-corresponding author , associate professor of immunology and microbiology at Scripps Research.

HIV’s envelope presents a particularly difficult target for vaccine development, Zwick added, because the virus displays so few spikes and camouflages them with sugar molecules so as to evade our immune system.

“All these features increase the dynamic variability that the HIV spike protein presents to the immune system,” said Lee, who also exploring virus structure and dynamics. “This is something that people in HIV vaccine development have grappled with from the very beginning — this virus mutates and changes itself astronomically and rapidly. Each time it infects an individual, you end up with literally thousands of different variants within that one individual, and if you look across populations, it’s multiplied even more.”

In fact, in February, an even more deadly strain of HIV was found to have been . Luckily, while the strain is a “highly virulent variant,” it still responds to treatment.

“This is just another reminder that these viruses are always changing, so we need scientists to continue studying them,” Zwick said.

Co-authors are Vidya Mangala Prasad, former acting instructor at 91̽��School of Pharmacy, currently at the Indian Institute of Science; Daniel Leaman, Department of Immunology and Microbiology, The Scripps Research Institute; Klaus Lovendahl, Jacob Croft and Edgar Hodge, Department of Medicinal Chemistry, 91̽��School of Pharmacy; and Mark Benhaim, who worked on the project as a graduate student at UW.

This research was funded by several National Institutes of Health grants, the James B. Pendleton Charitable Trust and a 91̽��Proteomics Resource grant. A grant from the Bill & Melinda Gates Foundation also supported portions of this work.

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For more information, contact Lee at kklee@uw.edu and Zwick at zwick@scripps.edu.

Gimbel, an implementation scientist at the 91̽��School of Nursing, tested her hypothesis and found that smartphone applications, or apps, have the potential to improve efforts to combat HIV/AIDS and other diseases both in the African subcontinent and around the world. By designing software for mobile devices, Gimbel believes that will empower nurses by putting cutting-edge tools into their hands.

“I want to get nurses more engaged in the process of analyzing and using their data,” said Gimbel, who holds an adjunct appointment in the Department of Global Health.

Nurses provide care but also collect data. If they can be actively engaged in using that data, it can lead to improvements in data quality and, ultimately, better health outcomes, Gimbel said.

In a paper published in the September issue of Current HIV/AIDS Reports, Gimbel and her co-authors evaluated the current use of mobile phones and tablets in HIV-related care in low- and middle-income countries around the world. The use of this new technology in the health care system is also known as “mHealth.”

The authors found that a larger selection of phone applications, or apps, are needed to improve the tremendous resources that have been provided to improve HIV/AIDS prevention, care and treatment. And the applications must be designed to be used by huge volumes of users, in other words, to scale.

“Scientists, researchers and practitioners increasingly are borrowing tools from engineering and bringing them to the intersection of quality improvement and health,” Gimbel said.

Leveraging existing health resources – including smartphones – will help nurses work better and smarter, Gimbel said. Nearly 100 percent of the world’s population lives within reach of a cellphone signal, and many nurses in developing economies are able to afford a smartphone. Smartphones can run apps to collect and transmit data of all kinds, from patient adherence information to monitoring drug protocols, and more.

Gimbel and her team focused on HIV/AIDS as opposed to other chronic conditions due to its burden and the amount of resources that have been invested to fight the pandemic. “It’s our laboratory to understand how to make chronic care systems work. So HIV is our testing ground,” Gimbel said. “It has a lot of commonalities with other chronic diseases.”

Now, Gimbel argues, academics and industry must work collaboratively to develop scalable solutions for mHealth innovations to combat HIV and other diseases.

Co-authors include Nami Kawakyu, Hallie Dau and Jennifer A. Unger, all of the UW.

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For more information, contact Gimbel at sgimbel@uw.edu or 206-616-5064.

While the Ebola outbreak in West Africa has captured the world’s attention, it’s just one of many emerging infections that we must confront in the coming years, said , 91̽��professor of microbiology. He leads Ebola research at a high-level biocontainment facility at the Rocky Mountain Laboratories in Montana.

“Ebola is not the only emerging virus; it’s just the most famous one,” Katze said. “There’s West Nile, which was never in North America before and now is everywhere. There’s Chikungunya virus, which had never been in the Americas, but now has spread through the Caribbean and has reached the southern United States. There’s SARS (Severe acute respiratory syndrome), which spread from Asia to Toronto and Vancouver, and there’s MERS (Middle Eastern Respiratory Syndrome) that still ongoing in Saudi Arabia and the Middle East. That epidemic isn’t over.

To be more agile in responding to emerging pathogens, Katze advocates for accelerated development of new drugs and vaccines.

Read more:��

Study helps explain why HIV causes lifelong infection

The persistence of HIV infection despite antiretroviral treatment depends partly on which human genes the virus integrates, according to a ��by researchers at the 91̽��schools of Public Health and Medicine, Seattle Children’s Research Institute, and Fred Hutchinson Cancer Research Center.

Read more:

Back-to-school tips to reset kids sleep routines

As the new school year approaches, School of Nursing sleep expert Teresa Ward, professor of parent and child nursing, offers advice on helping your children arrive rested each day and ready to learn and play.

Learn how kids establish good sleep habits:

91̽�� bioengineers have discovered a potentially faster way to deliver a topical drug that protects women from contracting HIV. Their method spins the drug into silk-like fibers that quickly dissolve when in contact with moisture, releasing higher doses of the drug than possible with other topical materials such as gels or creams.

“This could offer women a potentially more effective, discreet way to protect themselves from HIV infection by inserting the drug-loaded materials into the vagina before sex,” said Cameron Ball, a 91̽��doctoral student in bioengineering and lead author on a in the August��issue of .

The 91̽��team, led by bioengineering assistant professor , previously found that to release drugs. These new results build upon that research, showing that the fiber materials can hold 10 times the concentration of medicine as anti-HIV gels currently under development.

Oral pills are used in the U.S. for people who are considered at risk for HIV infection, and topical medications in the form of gels and films are just starting to be developed. These products would be placed inside the vagina before sexual intercourse, allowing the drug to dissolve and diffuse into the surrounding tissue. Called microbicides, the drugs must be given as a large dose to be effective minutes before sex.

But these topical drugs haven’t done well in clinical trials, partly because they aren’t always easy for women to use. Drugs in film form take at least 15 minutes to fully dissolve in the body, and the volume of gels must be large enough to deliver a full dose but small enough to prevent leakage. These factors can make microbicides difficult for a woman to use before sex, researchers said.

“The effectiveness of an anti-HIV topical drug depends partially on high-enough dosages and quick release,” Ball said. “We have achieved higher drug loading in our material such that you wouldn’t need to insert a large amount of these fibers to deliver enough of the drug to be helpful.”

The 91̽��team created the soft fibers using a process called . They first dissolved a polymer and combined it with a drug, maraviroc, and other agents often used in pharmaceuticals that help a material become more water soluble and dissolve quicker. Maraviroc currently is used to treat symptoms of HIV for people who already have the virus.

The syrupy substance is then charged with a high-voltage generator and passed through a syringe. The electric charge on the substance’s surface causes it to form a long string from the syringe, where it whips around – or spins – before collecting on an electrically grounded surface. A palm-sized swatch of the fabric takes about five minutes to make.

Anti-HIV drugs such as maraviroc can take a while to dissolve, so the researchers looked at different ingredients for the fiber that would allow for the highest concentration of drug with the fastest-possible release in the body. Because the electrically spun fibers have a large surface area, researchers were able to create samples in which nearly 30 percent of the mass was composed of the drug itself. In topical gels, the drug makes up only about 3 percent of the total mass.

By adjusting the ingredients in the fibers, researchers were able to dissolve the drug in about six minutes, no matter how much drug mass was in the fiber.

The research team says the soft, dissolving fibers could be rolled into a cardboard tampon applicator for insertion or built into the shape of a vaginal ring, similar to those used for contraception. The material can accommodate different anti-HIV drugs and the team is testing several others for effectiveness.

“We think the fiber platform technology has the capability of being developed into multifunctional medical fabrics that address simultaneously challenges related to biological efficacy and user preferences,” Woodrow said.

Researchers are currently focused on developing prototypes based on user guidance that can be tested for safety and efficacy in animal models.

This research was funded by the National Institutes of Health.

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For more information, contact Ball at cameron.s.ball@gmail.com and Woodrow at woodrow@uw.edu.

Grant numbers: NIH AI098648, NIH P41 EB-002027.

Alzheimer’s Coordinating Center director talks about burden of dementia

91̽��epidemiologist William Kukull has devoted his public health career to the study of Alzheimer’s disease. In a personal profile, he mentions what led him to this field, and the ramifications of the disorder as more Americans live longer.

Blood sugar drives brain’s response to sight of food

Our brain’s response to the sight of food appears driven more by our blood sugar level at the moment than our upbringing or genetics, according to a 91̽��study of identical twins.

“The finding suggests our brains have a way to override genetic inheritance, upbringing and habits to respond to our immediate nutritional needs,” said Dr. , 91̽��assistant professor of medicine, who led the research.

Harborview trauma director discusses brain-injury study, consent law exemptions

Harborview is one of 10 U.S. and Canadian trauma centers planning a study of a therapeutic drug for patients suspected of having sustained a traumatic brain injury. Harborview’s trauma director explains how the public is being notified about the study before it starts, due to consent law exemptions for trauma patients who are unconscious.

Workshop is first mind-meld of UW, Allen Brain Institute

For the first time, two Seattle brain research powerhouses are collaborating to teach the next generation of neuroscientists. The UW’s Computational Neuroscience program and the Allen Institute for Brain Science will jointly offer��a “Summer Workshop on the Dynamic Brain” Aug. 24 through Sept. 7 at Friday Harbor Laboratories.

Physician offers advice to peers on avoiding burnout

Health professionals devoted to caring for others sometimes neglect their own needs for restorative rest and relaxation. A 91̽��physician offers tips for keeping mental and emotional exhaustion at bay in a demanding career.

AIDS-free generation is aim of new guidelines for clinician

Many tools to prevent HIV are available but are not being used like they should. An interdisciplinary panel of experts created a simple framework of best clinical practices to try to achieve an AIDS-free generation. The guidelines, published in the Journal of the American Medical Association, integrate biomedical advances and evidence-based behavioral interventions for people with HIV or at high risk for HIV infection.

The National Institute of Allergy and Infectious Diseases of the National Institutes of Health has announced the award of a five-year, nearly $15 million contract, including the exercise of all options, to the 91̽��for the Nonhuman Primate Core Functional Genomics Laboratory for AIDS Vaccine Research and Development.

The lab will apply leading-edge biotechnology, biocomputing tools and systems biology approaches to conduct this service. It is anticipated to make inventive improvements in vaccine services and assays.

The principal investigator is Dr. Michael Katze, a 91̽��professor of microbiology who pioneered systems biology to understanding immune responses to infections. He and his colleagues examine the network of responses and interactions between pathogens and their hosts, as well as the factors that influence the dynamics of this struggle.

“The AIDS vaccine field is in need of new approaches. The methods we use allow us to understand the gene expression changes that correlate with vaccine efficacy and will help to design better vaccines,” Katze said.

Their laboratory will receive specimens obtained from ongoing and new high-priority preclinical non-human primate studies conducted in the National Institute of Allergy and Infectious Diseases Division of AIDS Simian Vaccine Evaluation Units and other Division of AIDS -supported preclinical non-human primate studies across the country. ��It will become the fourth Simian Vaccine Evaluation Units Core Lab in this effort to end the AIDS epidemic. The existing Simian Vaccine Evaluation Units Core Labs, located at other institutions, cover other aspects of AIDS vaccine preclinical research in non-human primates: ��the Humoral Immunology Core Lab, the Cellular Immunology Core Lab, and the Viral RNA Core Lab.

The new 91̽��Non-Human Primate Core Functional Genomics Lab will test specimens to generate specific genomic expression profiles using approaches developed by 91̽��microbiologist Dr. Robert Palermo and other 91̽��research scientists. These profiles are a time-record of gene activity, and rapidly examine many genes at once. The profile reveals those segments of the organism’s genome that are being dynamically utilized. The transcription of information coded in the DNA is the first step in producing a protein to carry out a biological function.

After measuring how experimental conditions alter which genes are turned on or off, a systems-level view is derived. This analysis uses sophisticated mathematical techniques, interaction networks, and computer modeling. ��In this approach, other types of data from the vaccine studies are integrated with the genomic expression profiles to find potential predictive signatures. The list of RNA molecules discovered during such characterizations offer clues to the events taking place inside and around living cells.

In evaluating potential AIDS vaccines, data analyzed in this way may point to gene signatures that suggest how much protection a vaccine is expected to provide against HIV. Checking for and measuring gene signatures after vaccination and virus exposure could in part explain a vaccine’s effectiveness in preventing or controlling an infection by illuminating the details of the immune mechanisms evoked by the vaccine.

Palermo commented:�� “The vision of the Division of AIDS at the National Institute of Allergy and Infectious Diseases in establishing this Core is very exciting.�� The work will inform not only the efforts of individual investigators, but will result in a compendium of such data across many studies and conditions. This will enable sophisticated computational approaches that are dependent on having very large amounts of data, and ideally will lead to insights not accessible with the results of a single study.”

The activities of the 91̽��Non-human Primate Core Functional Genomics Lab will contribute to the many National Institute of Allergy and Infectious Diseases-funded efforts that target discovering effective preventive vaccines against AIDS. ��National Institute of Allergy and Infectious Diseases supports testing a variety of candidate AIDS vaccines, and is exploring ways to optimize their ability to elicit immune responses that will prevent infection or control virus replication.

The National Institutes of Health contract number for the 91̽��Core Functional Genomics Lab is HHSN272201300010C.

, professor and chair of the 91̽��Department of Global Health, won the prestigious 2013 Canada Gairdner Global Health Award for his work in sexually transmitted diseases, the Gairdner Foundation March 20.

The award, valued at $100,000 Candian (about $97,300 U.S.) is one of the world’s most esteemed prizes for medical research. Since 1959, of the 312 individuals presented with a Canada Gairdner Award, 80 have gone on to receive a Nobel Prize. Holmes said he would contribute the money to the 91̽��.

Holmes was awarded the prize for his “global scientific contributions to the field of sexually transmitted disease and their effective treatment and prevention.” He becomes the 10th 91̽��faculty member to win a Gairdner Award.

The Gairdner Foundation, in citing the award, said that today more than 35 sexually transmitted diseases have been discovered. Holmes and the scientists he mentored are working on approximately 20 of these.

“Dr. Holmes assisted in defining the causes of many major diseases and through leading numerous clinical trials, has paved the way for many standard-of-care therapies used to treat STDs today,” the foundation said in a release.

John Dirks, president and scientific director of the Gairdner Foundation, told The Lancet that Holmes “brought to medicine and public health the proper means of diagnosing, treating, and preventing STDs and of understanding their epidemiology. In addition, his amazing gift of mentorship launched so many trainees to the forefront of the global health scene, which, thanks in great measure to their achievements, is now a flourishing discipline in its own right. Holmes’ huge lifetime contribution has no parallel. Among the many mountains on the public health landscape he stands out as an Everest.”

Holmes holds the He founded and directs the , which provides patient care, training and education, research and international technical assistance in the field of sexually transmitted diseases. Holmes is also head of Infectious Diseases at Harborview Medical Center.

Read The Lancet .

Watch a brief of Holmes on advances in AIDS survival.

A 91̽�� team has developed a versatile platform to simultaneously offer contraception and prevent HIV. Electrically spun cloth with nanometer-sized fibers can dissolve to release drugs, providing a platform for cheap, discrete and reversible protection.

The research was published this week in the Public Library of Science’s open-access journal . The Bill & Melinda Gates Foundation last month awarded the 91̽��researchers almost $1 million to pursue the technology.

“Our dream is to create a product women can use to protect themselves from HIV infection and unintended pregnancy,” said corresponding author , a 91̽��assistant professor of bioengineering. “We have the drugs to do that. It’s really about delivering them in a way that makes them more potent, and allows a woman to want to use it.”

uses an electric field to catapult a charged fluid jet through air to create very fine, nanometer-scale fibers. The fibers can be manipulated to control the material’s solubility, strength and even geometry. Because of this versatility, fibers may be better at delivering medicine than existing technologies such as gels, tablets or pills. No high temperatures are involved, so the method is suitable for heat-sensitive molecules. The fabric can also incorporate large molecules, such as proteins and antibodies, that are hard to deliver through other methods.

At a lab meeting last year, Woodrow presented the concept, and co-authors Emily Krogstad and Cameron Ball, both first-year graduate students, pursued the idea.

They first dissolved polymers approved by the Food and Drug Administration and antiretroviral drugs used to treat HIV to create a gooey solution that passes through a syringe. As the stream encounters the electric field it stretches to create thin fibers measuring 100 to several thousand nanometers that whip through the air and eventually stick to a collecting plate (one nanometer is about one 25-millionth of an inch). The final material is a stretchy fabric that can physically block sperm or release chemical contraceptives and antivirals.

“This method allows controlled release of multiple compounds,” Ball said. “We were able to tune the fibers to have different release properties.”

One of the fabrics they made dissolves within minutes, potentially offering users immediate, discrete protection against unwanted pregnancy and sexually transmitted diseases.

Another dissolves gradually over a few days, providing an option for sustained delivery, more like the birth-control pill, ��to provide contraception and guard against HIV.

The fabric could incorporate many fibers to guard against many different sexually transmitted infections, or include more than one anti-HIV drug to protect against drug-resistant strains (and discourage drug-resistant strains from emerging). Mixed fibers could be designed to release drugs at different times to increase their potency, like the prime-boost method used in vaccines.

The electrospun cloth could be inserted directly in the body or be used as a coating on vaginal rings or other products.

Electrospinning has existed for decades, but it’s only recently been automated to make it practical for applications such as filtration and tissue engineering. This is the first study to use nanofibers for vaginal drug delivery.

While this technology is more discrete than a condom, and potentially more versatile than pills or plastic or rubber devices, researchers say there is no single right answer.

“At the time of sex, are people going to actually use it? That’s where having multiple options really comes into play,” Krogstad said. “Depending on cultural background and personal preferences, certain populations may differ in terms of what form of technology makes the most sense for them.”

The team is focusing on places like Africa where HIV is most common, but the technology could be used in the U.S. or other countries to offer birth control while also preventing one or more sexually transmitted diseases.

The research to date was funded by the National Institutes of Health and the UW’s . The other co-author on the paper is Thanyanan Chaowanachan, a 91̽��postdoctoral researcher and longtime HIV expert.

The team will use the new Gates Foundation grant to evaluate the versatility and feasibility of their system. The group will hire more research staff and buy an electrospinning machine to make butcher-paper sized sheets. The expanded team will spend a year testing combinations that deliver two antiretroviral drugs used to treat HIV and a hormonal contraceptive, and then six months scaling up production of the most promising materials.

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For more information, contact Woodrow at 206-685-6831 or woodrow@uw.edu.

on Partners PrEP study

Global Advocacy for AIDS Prevention

New England Journal of Medicine��

International Clinical Research Center ()

The U.S. Food and Drug Administration decided today, July 16, ��to approve the use of an HIV treatment drug for reducing the risk of acquiring HIV.

Following the recommendation of the Antiviral Drugs Advisory Committee made on May 10, the FDA approved the medication generically known as combination emtricitabine/tenofovir disoproxil fumarate (FTC/TDF, branded as Truvada®), for HIV prophylaxis for people who test HIV negative.�� Truvada® is manufactured by Gilead Sciences Inc. in Foster City, Calif., and is currently prescribed with other HIV drugs for treatment of those infected with the virus.

In evaluating whether to allow Truvada® to be prescribed for HIV prevention purposes for those who are not HIV infected, the FDA reviewed the evidence from two studies – the largest of which was conducted by the University of Washingtons International Clinical Research Center (ICRC).

The study, known as the Partners PrEP Study (PrEP is short for pre-exposure prophylaxis), is led by the UWs International Clinical Research Center.�� Nine research sites in Kenya and Uganda enrolled 4,758 serodiscordant heterosexual couples, in which one partner has HIV and the other does not, and followed them monthly for up to three years.

The Partners PrEP Study is the largest study of its kind to date and found that FTC/TDF reduced the chances of HIV transmission by 75 percent. Not surprisingly, the protective effect was higher when the drug was taken regularly, without missing doses when analyses considered whether participants had detectable levels of the medication in their blood, the protective effect was approximately 9) percent.�� Results of the study were published July 11 ��in The New England Journal of Medicine.

“HIV serodiscordant couples recognized their risk, were highly motivated to take PrEP, and the medication offered high levels of protection for both women and men,” said Dr. Connie Celum, director of the ICRC and a 91̽��professor of global health.

Dr. Jared Baeten, co-chair and medical director for the study and an associate professor of global health at UW, said that the approval of Truvada for use in non-infected people would be a milestone for HIV prevention.

“With the ongoing AIDS epidemic in Africa and the steady number of HIV infections in the United States, it is imperative to determine how this effective prevention strategy can be made available to those at greatest risk worldwide,” said Baeten.

An estimated 7,400 people are infected every day with HIV, according to UNAIDS . More than 60 million have been infected with HIV since the pandemic began. In the United States, new infections have remained steady at 50,000 a year.

In Africa, AIDS is the leading cause of death and HIV discordance in couples is very common, said Celum. She added, “Studies in Africa have found that the partner of an HIV-infected person has about a 50 percent chance of being infected.�� Finding new strategies to reduce the risk of HIV transmission in HIV serodiscordant couples is a high public health priority.”

The FDA approval is central to United States-based prescribing laws, but the approval can be a strong signal to regulatory bodies around the globe that FTC/TDF for HIV prophylaxis is safe and effective.�� CDC and WHO guidance are currently being finalized.

The medication used in the Partners PrEP Study, combination emtricitabine (200 mg) / tenofovir disoproxil fumarate (300 mg), is marketed by Gilead Sciences, Inc. under the brand name Truvada®. The medication is available generically in many countries at prices as low as approximately 25-30 cents (USD) per tablet. Gilead Sciences donated study medication, but did not provide funding or otherwise participate in the design, implementation, or analysis of the Partners PrEP Study.�� The ��Bill & Melinda Gates Foundation funded the study.

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