The first trial was a huge disappointment. The experimental vaccine, developed by U.S. drugmaker Merck, failed to prevent HIV infections so miserably, Merck halted the trial in September 2007. Two years later, results from the second trial were more promising. The trial was conducted in Thailand, involved more than 16,000 volunteers and used a combination of two vaccines. But three months after the results were released, questions persist whether the modest preventative effect of the Thai vaccine combo was real or due to chance.

Dr. Myron Cohen

Dr. Myron Cohen, a leading HIV/AIDS expert at the University of North Carolina, considers the results from the Thai vaccine trial “the first glimmer of hope” that there is a way to stop the spread of HIV/AIDS, particularly in poor countries.

Cohen, who also serves in a senior leadership position at the National Institutes of Health Center for HIV/AIDS Vaccine Immunology, also known as CHAVI, was one of two speakers Thursday at the N.C. Biotechnology Center in Research Triangle Park. The Triangle Global Health Consortium invited him and Kenneth Schulz, head of the biostatistics division at Family Health International in Durham, to give their takes on the Thai trial.

“Diseases come and go,” said Cohen. “There must be an end to the AIDS/HIV epidemic.” But he and Schulz agreed the Thai trial has yet to provide clues how to get there.

The failure of the Merck trial was such a great disappointment, because at the time the Merck vaccine was considered the best shot at preventing an HIV infection. It was designed to stimulate the production of white blood cells, or T-cells, and train them to attack and kill the AIDS virus once it entered the bloodstream. Researchers had invested much hope in the killer T-cell approach. Efforts to come up with a vaccine that stimulates neutralizing antibodies – an approach used in flu, polio and measles vaccines - had gone nowhere because of HIV’s ability to rapidly adapt.

The Thai trial appears to redirect researchers’ attention to the antibody approach, Cohen said. The vaccine combo was designed to first alert killer T-cells and then boost the antibody response. Volunteers who received the combo shots had about a 31 percent lower HIV infection rate than volunteers who received dummy shots. But the trial, which lasted three years and cost $105 million, doesn’t answer why.

Indeed, the Thai trial combined immune response boosters that either didn’t work in previous trials or had not been tested alone.

Dr. Alan Bernstein

So, do the Thai trial results matter, and how? Cohen said he might find answers as he evaluates blood samples from the trial, which will take about a year. But for now, nobody knows.

His concerns echo an assessment another AIDS vaccine expert made of the puzzling results two months ago at the AIDS Vaccine 2009 conference in Paris.

“It’s a sign of our own ignorance of what’s really going on scientifically and biologically and, therefore, the need to think deeply of how to go forward,” Dr. Alan Bernstein, executive director of the Global HIV Vaccine Enterprise in New York, said during a presentation at the conference.

There’s no doubt, research will continue to look for an HIV/AIDS vaccine that is safe and works. As a matter of fact, several are being tested now and researchers are looking into repeating the Thai trial in Africa.

More than 33 million people worldwide are HIV positive, including an estimated 1.2 million in the U.S., according to 2008 figures of the World Health Organization and UNAIDS, the United Nations Program on HIV/AIDS. Every day, more than 7,000 people worldwide are newly infected with HIV and about 5,500 die from AIDS.

About two dozen antiviral medicines are available to suppress HIV, but treatment to keep the virus in check is expensive and carries the risk of side effects. Without a cure, a vaccine that prevents HIV infection appears to be the best chance to stop HIV/AIDS in its tracks.

So what should HIV/AIDS vaccine researcher focus on next? The response to this question will not only determine key scientific opportunities but also where money for research goes, Bernstein said. For example, funding for two key initiative, CHAVI and the Collaboration for AIDS Vaccine Discovery, or CAVD, is up for renewal.

In 2006, CHAVI and CAVD received a total of more than $500 million from the NIH and the Bill and Melinda Gates Foundation over five years. UNC and Duke University play leading roles in both organizations.

Monday

-6 p.m. to 8 p.m.

Irregardless Cafe, 901 W. Morgan St., Raleigh

CED’s renewable energy business network reception

More information here.

Tuesday

- 11 a.m. to noon

National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park

Rall Bldg., Rodbell A

Biostatistics Branch Seminar: Ordinal-dominance-curve-based inference for stochastically ordered distribution

Speaker: Ori Davidov, University of Haifa

- Noon to 1:30 p.m.

Research Triangle Park headquarters, 12 Davis Drive, Research Triangle Park

TARDC lucheon

Speaker: Dr. Richard Stack, president of Synecor

Cost: $35 for non-members

- Noon to 1:30 p.m.

Sigma Xi, 3106 E. Hwy. 54, Research Triangle Park

Pizza luncheon: An Empire Lacking Food: The Astonishing Existence of Life on the Deep Sea Floor

Speaker: Craig McClain, marine biologist and assistant director of science at the National Evolutionary Synthesis Center in Durham

RSVP required at cclabby@amsci.org

Wednesday

-9 a.m. to 4 p.m.

Sheraton Hotel, 1 Europe Drive, Chapel Hill

National NIEHS event: Asbestos: A science-based examination of the mode of action of asbestos and related mineral fibers

Thursday

-7:30 a.m. to 9 a.m.

N.C. Biotechnology Center, 15 T. W. Alexander Drive, Research Triangle Park

Triangle Global Health Consortium breakfast discussion: Validation of clinical trial results – the clinician’s vs statistician’s interpretation of the Thailand HIV/AIDS vaccine study

Facilitators: Ken Schulz, vice president of Family Health International’s quantitative sciences department and author of the CONSORT guidelines for reporting clinical trials, and Dr. Myron S. Cohen,  professor of medicine, microbiology and immunology and public health at the University of North Carolina at Chapel Hill.

- 10 a.m. to 11 a.m.

NIEHS, 111 T.W. Alexander Drive, Research Triangle Park

Rall Bldg. Room D450

Seminar: The complex lives of the glucocorticoid receptors in health and disease

Speaker: John Cidlowski

-2:30 p.m.

N.C. State University, 105 Schaub Hall

Dept. of Food, Bioprocessing and Nutrition Sciences Seminar: Use of Predictive Microbiology Information Portal, the USDA-Pathogen Modeling Program & ComBase

Speaker: Vijay K. Juneja, lead scientist, Microbial Modeling and Bioinformatics, Microbial Food Safety Research Unit, USDA-Agricultural Research Service

Friday

- 9 a.m.

N.C. State University, Stephens Room, 3503 Gardner Hall, Raleigh

Dept. of Microbiology Seminar: Characterization of the prostaglandin E2 response to poxvirus infection, and evaluation of the anti-poxvirus activity of tetra-O-methyl nordihydroguaiaretic acid

Speaker: Justin J. Pollara, NCSU Microbiology

- 9 a.m.

N.C. State University, 105 Schaub Hall, Raleigh

Dept. of Food, Bioprocessing and Nutrition Sciences Seminar: Development of molecular-based methods to capture and detect salmonella and campylobacter in complex samples matrices

Speaker: Hari Prakash Dwivedi

For a closer look at what this means, Science in the Triangle talked to four North Carolinians familiar with battling HIV:

• Dr. Charles Hicks, an infectious disease specialist at Duke University who started his career in San Francisco in 1979.
• James Hayes, who has been HIV-positive since probably 1982 and is part of research at Duke to develop a vaccine.
• Dr. Michelle Collins Ogle, who first encountered the disease in African-American babies in the late 1980s and has treated HIV/AIDS patients in rural North Carolina for about 10 years.
• John Paul Womble, HIV-positive and the interim executive director of the Alliance of AIDS Services in Raleigh.

RTP researchers have been at the forefront of developing breakthrough treatments since the early 1980s – from AZT, the first drug on the market, to current attempts of developing a vaccine. (More on the R&D efforts in RTP here.)

Watch Hicks talk about the early days, before AZT came to market in 1987 and drug cocktails marked a turning point in 1996, and why a cure is becoming possible. Part 1 and part 2.

Among the treatments discovered and developed in RTP is Fuzeon. Now, the injectible drug is being replaced by newer, oral medicines, but in 1999 Fuzeon changed Hayes’ life. He was one of the first patients to receive Fuzeon while it was still being tested. Watch Hayes talk about why HIV/AIDS is not like other chronic diseases. Part 1 and part 2.

Ogle treats about 250 HIV-positive patients at her clinic in Henderson, a rural area about 40 miles north of Durham. Two-thirds of her patients have no health insurance. Many read below an 8th-grade level. The number of HIV-positive women is rising, especially among 18- to 24-year-olds. Watch Ogle talk about dealing with HIV/AIDS in rural North Carolina. Part 1 and part 2.

John Paul Womble is one of Collins-Ogle’s patients, but he’s very different from the people she usually sees. Womble has health insurance, political influence and the means to get the best care available. He agrees with his doctor that being open and up-front about HIV/AIDS is paramount to corralling the spread of the disease. Watch Womble talk about finding out he was HIV-positive, the challenges of dealing with HIV/AIDS in the South and Jesse Helms’ granddaughter. Part 1 and part 2.

The interviews were videotaped in November and shown Dec. 1, World AIDS Day, at RTP headquarters during an event co-sponsored by RTI International and Triangle Global Health Consortium. The interviewer was Sabine Vollmer, the videographer was Jordan Mendys.

Targacept scores $1.24 billion deal

Targacept, a Winston-Salem drug development company, has agreed to sell the rights for an antidepressant it is working on to British drugmaker AstraZeneca. The deal is worth up to $1.24 billion and adds to an existing partnership the two companies have had since 2005 to develop treatments for cognitive disorders.

Antidepressants generate about $20 billion in sales worldwide, but more than half of all patients don’t respond to the most commonly prescribed medicines.

This is the second large deal Targacept has signed with a British pharmaceutical giant. Two years ago, GlaxoSmithKline, which has its U.S. headquarters in Research Triangle Park, agreed to pay up to $1.5 billion for the right to experimental painkillers Targacept was developing. One of the painkillers failed a clinical trial and in March, Targacept mothballed it.

Under the GSK and the AstraZeneca deals, payments are dependent on how effective the drugs are.

Quintiles to add debt to pay dividend

Quintiles Transnational will take on more debt to pay the three private investment firms that are its largest owners a fat dividend. According to Standard & Poor’s credit research, the Durham-based company, which helps drugmakers test and sell new medicines, plans to sell $400 million in bonds next week, adding to an existing debt load of $1.2 billion.

The majority of the bond sale will benefit TPG Partners of Fort Worth, Texas, Bain Capital of Boston and London-based 3i Group.

TPG helped finance a $1.7 billion management-led buyout that turned Quintiles into a privately held company six years ago. Bain Capital and 3i became large investors in Quintiles in 2007.

AIDS researchers dare to speak of a cure

Dr. Myron Cohen, an infectious disease specialist at the University of North Carolina, dared to speak of a cure for HIV, the virus that causes AIDS.

A laboratory experiment gives him hope.

More on Cohen’s talk, which he gave on World AIDS Day in Research Triangle Park, here.

HIV

It took a generation, but researchers now dare to speak of a cure for HIV, the virus that triggered the AIDS epidemic in the late 1970s.

A laboratory experiment with a special mouse gives them hope.

The experiment is described in a peer-reviewed journal the Public Library of Science published in January 2008.

Mice don’t usually get HIV infections. But the BLT (short for bone marrow/liver/thymus) mouse is different. It is specially bred and has human stem cells implanted. The cells infiltrate the BLT mouse’s organs and tissues, which allows the virus to take hold similarly to how it does in humans.

In the experiment, researchers gave BLT mice an HIV medicine called Truvada before they infected them with the virus. Truvada contains two drugs, Viread and Emtriva, that target the virus’ ability to get into the genetic information of a cell and hijack it. None of the mice on Truvada got sick.

Dr. Myron Cohen

“If you can cure a mouse, you can potentially cure a human,” said Dr. Myron Cohen, head of the division of infectious diseases at the University of North Carolina at Chapel Hill and director of the UNC Center for Infectious Diseases.

Cohen (photo at left) spoke Tuesday at the headquarters of the foundation that manages North Carolina’s Research Triangle Park. His talk was part of a World AIDS Day event that celebrated 30 years of HIV/AIDS research.

Much of the work was done in the RTP area, long a hotbed of research in infectious diseases.

AZT, the first HIV/AIDS drug that became available in 1987, was discovered and developed here. So were Fuzeon, the first drug to prevent HIV from entering a cell, and Emtriva, a drug developed by Triangle Pharmaceuticals in Durham. Both came to market in 2003.

GlaxoSmithKline, in whose RTP labs AZT was discovered, has formed a partnership with Pfizer to come up with new HIV/AIDS drugs, but GSK continues to center its HIV/AIDS drug research and development at its U.S. headquarters in RTP. Gilead Sciences, which became the leading HIV/AIDS drug developer after buying Triangle Pharmaceuticals six years ago, still maintains Triangle’s operations in Durham.

Cohen called the RTP area one of the focal points in HIV/AIDS research worldwide. In U.S. funding for HIV/AIDS research it comes in second only to the San Francisco Bay area, he said.

The RTP area is home to RTI International and Family Health International, research institutes trying to stem the spread of HIV in developing countries. UNC and Duke University run HIV/AIDS clinics in Africa and, with more than 1,500 patients each, two of the largest U.S. HIV/AIDS clinics.

UNC and Duke are also part of the Center for HIV/AIDS Vaccine Immunology, orCHAVI, a research consortium of universities and medical schools worldwide. Directed by Dr. Barton Haynes, head of Duke’s human vaccine institute, CHAVI stands to receive up to $483 million from the National Institutes of Health to overcome roadblocks in HIV vaccine development.

Lymphocyte (green) infected with HIV (red)

HIV is a master shapeshifter.

Once it has hijacked its host’s immune system, the virus’ genetic code begins to change almost immediately. The rapid-fire mutations can quickly make the virus resistant to medication and require changes in a patient’s drug regimen.

The mutations have also foiled many attempts to come up with a vaccine.

In the past five years, two RTP area companies have shelved ambitious HIV vaccine development projects. Two years ago, U.S. drugmaker Merck halted the first test of an experimental HIV vaccine in humans because the vaccine seemed to increase the risk of an HIV infection rather than decrease it.

Researchers in Thailand have had more luck. A study that tested a vaccine on 16,000 drug addict volunteers was the first with successful results. Study participants who received a series of shots were 31 percent less likely to get infected with HIV than those who , according to study results that were reported in September.

(More on the Thai HIV/AIDS vaccine study later. The study will be a topic of discussion Dec. 17 at the Triangle Global Health Consortium breakfast meeting.)

But the immunity lasted only about a year – a modest improvement at best considering about 30 million people worldwide are HIV positive and for every person who receives treatment six get infected with HIV.

MONDAY

4 p.m.
N.C. State University, Stephens Room, Gardner 3503
Dept. of Plant Pathology Seminar: Receptor kinase action in plant development and response to pathogens
Speaker: Dr. Steve Clouse, professor of horticultureal science, NCSU

4 p.m.
N.C. State University, Riddick 301, Raleigh
Physics Colloqium: The unfortunate Mr. Litvenenko: Radiobiology and toxicology of Po-210
Speaker: Richard E. Toohey, acting vice president for university partnerships, Oak Ridge Associated Universities

4 p.m. to 4:50 p.m.
N.C. State University, 2010 Biltmore Hall, Raleigh
Dept. of Forestry and Environmental Reseources Seminar: Restoration of nonriverine wet hardwood forests in North Carolina’s coastal plan
Speaker: Yari Johnson, graduate student, NCSU

TUESDAY

9 a.m. to 10 a.m.
National Institute of Environmental Health Sciences, 111 T.W. Alexander Drive, Research Triangle Park
Rall Bldg. Rodbell ABC
Keystone Science Lecture Series: Is it safe? Reporting personal exposures to individuals when health effects are uncertain.
Speaker: Dr. Julia Brody, Silent Spring Institute

11 a.m. to noon
NIEHS, 111 T.W. Alexander Drive, Research Triangle Park
Rall Bldg. Rodbell A
Biostatistics Branch Seminar Series: A statistical approach to projecting future climate
Speaker: Murali Haran, Penn State University

Noon to 1 p.m.
NIEHS, 111 T.W. Alexander Drive, Research Triangle Park
Rall Bldg. Executive Conference Room
Receptor Mechanism Discussion Group: Life and death and glucocorticoids
Speaker: Alyson B. Scoltock, biologist – molecular endocrinology, laboratory of signal transduction, NIEHS

4:30 p.m. to 7:30 p.m.
Research Triangle Park headquarters, 12 Davis Drive, Research Triangle Park
Techie Tuesday: World AIDS Day
Speakers: Dr. Myron Cohen, director of the UNC Center for Infectious Diseases; Nicole Fouche, executive director of the Triangle Global Health Consortium

Join RTP and partner organizations for a special Techie Tuesday to celebrate those addressing modern global health challenges such as HIV/AIDS through research and support services.

More information here.

WEDNESDAY

4 p.m. to 6 p.m.
NIEHS, 111 T.W. Alexander Drive, Research Triangle Park
Rall Bldg. Rodbell A
Triangle Magnetic Resonance Discussion Group
Speaker: Bruce Donald, Duke University

THURSDAY

10 a.m. to 11 a.m.
NIEHS, 111 T.W. Alexander Drive, Research Triangle Park
Rall Bldg. Room D450
Seminar: COX-2 dependent inflammation in cardiovascular and adipose tissue
Speaker: Charles Loftin, University of Kentucky

11 a.m. to noon
Webinar: Clean energy economy in the South
Speaker: Kil Huh, director of research, Pew Center on the States

In June, the Pew Center of the States released a state-by-state analysis that estimates the number of jobs in the clean energy economy from 1998 to 2007 and found a faster rate of increase than all jobs combined. Huh will discuss the results of the report, their implications and opportunities for the South.

For more information here and to register, here.

3 p.m.
N.C. State University, Schaub Hall, Raleigh
Dept. of Food, Bioprocessing and Nutrition Sciences: “Food Inc.,” the movie
Host: Dr. Lee-Ann Jaykus

3:30 pm to 5:00 pm
N.C. State University, 1216 Jordan Addition, Raleigh
Marine, Earth and Atmospheric Sciences Dept. Seminar: Basic research opportunities in the atmospheric boundary layer
Speaker: Walter Bach, director of atmospheric sciences, Army Research Lab

4 p.m.
N.C. State University, 101 David Clark Labs, Raleigh
Dept. of Biology Seminar Series: Systems genetics of complex traits in “drosophila”
Speaker: Trudy Mackay, genetics, NCSU

FRIDAY

9 a.m. to 10 a.m.
NIEHS, 111 T.W. Alexander Drive, Research Triangle Park
Rall Bldg. Rodbell B
Seminar: The impact of low-level mercury exposure on peripheral nerve function
Speaker: Alfred Franzblau

Geography of innovation

President Barack Obama has asked Congress to appropriate $100 million in fiscal year 2010 to renew economic development efforts at regional innovation hot spots.

A report supports those efforts, saying that areas such as the Silicon Valley, an information technology cluster, and biotech clusters in Boston and the Research Triangle Park area, are critical components of national competitiveness.

The federal government already funds about $150 billion of research and development per year.

North Carolina’s biotech industry, which is concentrated in the Triangle, is considered the third largest by number of companies. But the Triangle is also home to information technology and medical device clusters that together created more than 5,000 jobs between 1998 and 2006, according to the report.

Deals and regulatory actions

Bayer CropScience added a research collaboration to other recent deals aimed at coming up with better genetically modified crop seeds.

The German company, which has its U.S. headquarters in RTP, will partner with Precision BioSciences of San Diego. The deal is the third in a row to improve Bayer CropSciences’ ability to compete in the GM seeds market.

In recent weeks, the company bought rights from Texas Tech to improve the fiber quality from cotton seeds and announced it would buy its RTP-neighbor Athenix.

More about why Bayer CropScience is dealing here.

Other company news:

• Cornerstone Therapeutics, a Cary company specializing in respiratory treatments, received approval to buy the rights to an antibiotic from Oscient Pharmaceuticals, a Massachusetts company that has filed for Chapter 11 bankruptcy.
• The Food and Drug Administration told Pozen that the Chapel Hill drug development company’s request to approve PN400, a painkiller that causes fewer stomach ulcers, is complete. The FDA notice triggered a $10 million milestone payment from British pharma giant Astra-Zeneca, Pozen’s partner. Pozen filed the request in June and the FDA is expected to rule on it in 2010.
• BioDelivery Sciences International will close its research laboratory in Newark and consolidate operations at corporate headquarters in Raleigh. All four positions in Newark will be eliminated to save about $1 million in operating costs per year. More about BDSI here.
• Shares of Icagen get a lift after a mid-stage study shows that the Durham drug development company’s experimental asthma drug eases allergy-related attacks.

Reality shows aim at preventing HIV spread

Family Health International, a Durham organization that aims to improve public health worldwide, is behind two reality shows to prevent the spread of HIV.

“Bongo Star Search” is a competition for would-be pop stars in Tanzania and “You’re the Man” is a competition that challenges stereotypes of what it means to be a man in Cambodia.