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Research at A&M and Scripps finds HIV-killing compound

Last Updated on Monday, 28 November 2011 01:35 Written by admin Monday, 28 November 2011 01:35

COLLEGE STATION - A powerful topical preventative for HIV, the virus that causes AIDS, could be a step closer to clinical trials, thanks to a newly discovered molecular compound that research at Texas A&M University and the Scripps Research Institute shows dissolves the virus on contact.

The ability of the synthetic compound known as “PD 404,182″ to break apart the AIDS-causing virus before it can infect cells was discovered by Zhilei Chen, assistant professor in the university’s Artie McFerrin Department of Chemical Engineering, and her team of researchers. Their findings appear in the November online edition of “Antimicrobial Agents and Chemotherapy,” a journal of the American Society for Microbiology.

“This is a virucidal small-molecule compound, meaning that it has the ability to kill a virus; in this case that virus is HIV,” Chen says.

“Basically, it acts by breaking the virus open. We found that when HIV comes in contact with this compound, it breaks open and loses its genetic material. In a sense, the virus ‘dissolves,’ and its RNA becomes exposed.

Since RNA is pretty unstable, once it is exposed it’s gone very quickly and the virus is rendered non-infectious.”

In other words, the compound works by quickly ripping open the virus before it can inject its genetic material into a human cell. What’s more – and perhaps even more important – the compound, Chen explains, achieves this by acting on something within the virus other than its viral envelope protein, meaning that the virus can’t alter its proteins to bolster its resistance – something that’s made HIV notoriously difficult to treat.

“We believe this compound is not working on the viral protein of the viruses but on something else common in all the viruses on which we tested it – some cellular material common in these viruses,” Chen notes. “Because this compound is acting on a component that is not encoded by the virus, it will be difficult for the virus to evolve resistance against this compound.”

While not a cure for HIV, the compound demonstrates significant potential for use as a preventative, specifically in the form of a topical gel that could be applied in the vaginal canal, Chen explains.

“We conducted a number of tests to demonstrate that this compound remains active in vaginal fluid and is not rendered ineffective,” Chen says. “In the form of a vaginal gel, the compound would serve as a barrier, acting almost instantaneously to destroy the virus before it could infect a cell, thereby preventing HIV transmission from one person to another.”

Surprisingly, Chen and her team did not set out to discover an HIV preventative. Instead, they were conducting screenings of molecules for use in potential drug therapies targeting hepatitis C virus, which causes the dangerous and often fatal disease of the liver. Employing a screening system developed by Chen, the team screened thousands of molecular compounds, in search of those that could block aspects of the HCV life cycle.

During the course of the screenings, the team made an interesting discovery

- not only was PD 404,182 an HCV inhibitor, it also worked on lentiviruses (the group’s negative control in its experimental procedures). Intrigued by that finding, Chen then tested PD 404,182 on HIV, which itself is a lentivirus and found the compound to be even more effective on HIV than on HCV.

“We believe PD 404,182 acts through a unique and important mechanism,” Chen notes. “Most of the known virucidal compounds interact with the virus membrane, but our compound does not appear to interact with the virus membrane. Instead, it bypasses interaction with the membrane and still compromises the structural integrity of the virus.”

The ability of the compound to avoid interaction with the virus membrane is important because human cells have similar membranes, Chen notes. If the compound were to disrupt the structure of the virus membrane, it could also disrupt and ultimately kill human cells. PD 404,182 doesn’t interact with these membranes and is therefore a more attractive option for clinical treatment, Chen says.

As is the case with any potential pharmaceutical, several key steps are still needed before it winds up on drug store shelves. In addition to several rounds of animal studies to ensure the compound is safe for humans, further collaborations with chemists are needed to continue to improve the efficiency of the compound. Chen says. What’s more, Chen also plans to further explore the mechanism by which PD 404,182 breaks apart HIV.

This work is collaboration between Chen’s team, consisting of graduate students Ana Maria Chamoun and Rudo Simeon, postdoctoral associate Karuppiah Chockalingam, and Professor Philippe Gallay’s team at the Scripps Research Institute.

Source: http://www.kxxv.com/story/16095021/research-at-am-and-scripps-finds-hiv-killing-compound

Posted under Cell Analysis, Discoveries, Innovations and Patents, DNA Reasearch, HIV Research, New Drugs, North America, R & D, Reports, Research Projects, USA and Canada  |  Comments Off

Body & Mind – HEALTH U.S. Doctor Cautious About HIV Vaccine

Last Updated on Thursday, 29 September 2011 03:36 Written by admin Thursday, 29 September 2011 03:36

A New York City-based infectious disease specialist said a new vaccine developed by Spanish scientists, which could turn HIV into minor infection status, is reason to be cautiously optimistic.

Dr. Joseph Rahimian said Thursday news of an HIV vaccine is certainly exciting, but questions remain.

“An HIV vaccine has been the holy grail for infectious disease doctors for a very long time,” Rahimian said. “ There are a lot of people interested in creating one and obviously a lot of demand for it, so there would be a lot of excitement if this research is accurate.”

The vaccine, developed by scientists at the Spanish Superior Scientific Research Council (CSIC) in Madrid, works by training the immune system to detect HIV and learn how to combat the virus.

In a trial involving 30 healthy volunteers, scientists found that 90 percent of those who were given the MVA-B vaccine developed an immunity against the virus and 85 percent maintained this for a year.

Professor Mariano Esteban, from CSIC, said, “MVA-B vaccine has proven to be as powerful as any other vaccine currently being studied, or even more.”

He said the vaccine was like showing the body a picture of the HIV, “so that it is able to recognize it if it sees it again in the future.”

“If the virus enters the body and tries to develop in a cell, the immune system is ready to inactivate the virus and destroy the infected cell,” he added. Scientists hope that if bigger trials are successful, HIV would no longer cause AIDS and would be much less contagious.

‘”If this genetic cocktail passes Phase II and Phase III future clinic trials, and makes it into production, in the future HIV could be compared to herpes virus nowadays,” according to the study.

However, Rahimian said this study needs much more room to grow.

“The population that they used is very small, and they followed them out to one year. So one important question is how long does this last for? A vaccine that has to be given repeatedly every year is less exciting than a vaccine that can give long-term immunity,” he said.

On the other hand, Rahimian pointed out there are some vaccines given every year, which are successful, like the flu shot.

“I would say many people have tried to create vaccines, and it is a very difficult task, so any enthusiasm for a successful vaccine is guarded,” he said.

Source: http://www.foxnews.com/health/2011/09/29/new-vaccine-could-turn-hiv-into-minor-infection/

Posted under Cell Analysis, Discoveries, Innovations and Patents, Drug Development, HIV Research, Medicinal Chemistry, New Drugs, New Products, Press Releases, R & D, Reports  |  Comments Off

Daily pill can prevent HIV infection

Last Updated on Thursday, 14 July 2011 11:36 Written by admin Thursday, 14 July 2011 11:36

The partners of people who have HIV can protect themselves from infection by taking a once-daily pill, two groundbreaking studies in Botswana, Kenya and Uganda have shown.

The discovery could bring work to combat Aids close to a “tipping point”, experts say. Attempts to promote condom use to protect against HIV in the hardest-hit parts of the world, and particularly Africa, have hit cultural barriers and had limited success.

But now it appears that men or women who know – or suspect – their partner has HIV could protect themselves, secretly if necessary. The larger study, involving 4,758 “discordant” couples (where one has HIV but the other has not) in Kenya and Uganda, led by the University of Washington’s International Clinical Research Centre, shows that those taking a single daily tablet of the Aids drug tenofovir had 62% fewer infections and those who took a pill combining tenofovir and emtricitabine had 73% fewer infections than those who took a placebo pill.

The drugs have few side-effects, which is important if they are to be given to healthy individuals. Both are made by Gilead, which has licensed their manufacture to generic companies in the developing world, allowing them to produce cheap copies – so this is a relatively inexpensive intervention.

“This study demonstrates that antiretrovirals are a highly potent and fundamental cornerstone for HIV prevention and should become an integral part of global efforts for HIV prevention,” said Dr Connie Celum, professor of global health and medicine at the university and principal investigator of the study, known as the Partners PrEP Study, which was funded by the Bill and Melinda Gates Foundation.

The second study in Botswana was conducted by the United States Centres for Disease Control. It followed 1,200 heterosexual men and women without HIV who received either a once-daily tenofovir/emtricitabine tablet or a placebo pill. The antiretroviral tablet reduced the risk of acquiring HIV infection by roughly 63% overall.

“This is a major scientific breakthrough which re-confirms the essential role that antiretroviral medicine has to play in the Aids response,” said Michel Sidibé, Executive Director of the Joint United Nations Programme on HIV/Aids (UNAids). “These studies could help us to reach the tipping point in the HIV epidemic.”

The news follows hard on the heels of another very significant finding – that people with HIV who are taking combinations of antiretroviral drugs not only stay healthy themselves but are unlikely to infect their partner.

The two pieces of research give a massive boost to the cause of rolling out more Aids drugs and treating people at the earliest stage of their illness.

“Effective new HIV prevention tools are urgently needed, and these studies could have enormous impact in preventing heterosexual transmission,” said Dr Margaret Chan, WHO’s director general. “WHO will be working with countries to use the new findings to protect more men and women from HIV infection.”

Source: http://www.guardian.co.uk/world/2011/jul/14/hiv-daily-pill-breakthrough

Posted under Antibiotics, Cell Analysis, Discoveries, Innovations and Patents, Drug Development, HIV Research, Medicinal Chemistry, New Drugs, New Products, Press Releases, R & D, Reports  |  Comments Off

Hemophilia Is Target of Therapy on Genome

Last Updated on Monday, 27 June 2011 11:13 Written by admin Monday, 27 June 2011 11:13

Researchers using a new technique for editing the genome of living cells have shown that they can cure hemophilia in mice, at least in principle, with a couple of injections that carry out the “cut” and “paste” operations needed to insert a corrective gene.

This is the first time this genome-editing technique has succeeded in a live animal. Along with other applications, like two AIDS treatments in preliminary stages, the new technique could be the decisive improvement that gives credibility to the long-struggling field of gene therapy.

“This may well revolutionize the field, but it won’t do so overnight,” said Dr. Katherine A. High of the Children’s Hospital of Philadelphia, the research team leader. “Any novel kind of therapeutic takes time to develop.”

The essence of the technique is the molecular scissors custom-designed to cut the genome at a unique site. This allows the corrective gene to be inserted at the right place in a chromosome.

In previous forms of gene therapy, corrective genes have been inserted into the genome at random sites, for lack of the ability to control where they go. This approach means they are not under their natural control systems and, worse, may be inserted in the middle of some other gene that they disrupt.

“There’s a huge interest in this,” said Dr. Mark A. Kay, a gene therapist at the Stanford University School of Medicine. The genome editing approach “could be game-changing in some applications,” he said.

The technique depends on natural agents called zinc finger proteins whose role is to bind to specific sites on the genome and control adjacent genes. By mixing and matching the DNA of different natural zinc finger proteins, researchers can create artificial zinc fingers for any chosen target site on the genome.

In their genome-editing role, the zinc fingers are attached to a DNA-cutting enzyme derived from a bacterium. When a pair of zinc finger proteins line up on opposing strands of DNA, their DNA cutters face each other and scissor the DNA apart.

The zinc finger technique has been developed by Sangamo BioSciences and by academic researchers who belong to the Zinc Finger Consortium. “We are fairly inundated with requests,” said Philip D. Gregory, Sangamo’s chief scientific officer.

Sangamo designed the zinc finger pairs for Dr. High’s hemophilia project. But the fingers are designed to cut the human Factor 9 gene, not the mouse version, which has a different sequence of DNA units. So Dr. High genetically engineered a strain of hemophiliac mice that carry a mutated version of the human Factor 9 gene in place of their own.

After the cut-and-paste operation, the mice possessed a good working copy of human Factor 9, producing enough to make their blood clot much faster, and well enough to prevent hemophilia, Dr. High and her colleagues report in the journal Nature. To show that the new gene was stably incorporated into cells, they then cut out part of the mice’s livers. The liver regenerated from existing cells, retaining their ability to produce good copies of Factor 9.

Dr. High said it was too soon to try the technique in people, given that an adequate treatment for hemophilia already exists. She plans to test it next in dogs, which are a standard model for new hemophilia treatments. One of the possible problems with the technique is that the zinc fingers sometimes cut at sites other than the intended target site.

Dr. High said that besides hemophilia, the zinc finger technique could address many other liver-based genetic diseases.

Zinc fingers are being used in a different way in a treatment for AIDS, at present in early clinical trials. The fingers are used to disrupt a gene called CCR5, which makes the receptor used by the AIDS virus to gain access to cells. People with no CCR5 receptor are naturally immune to AIDS.

The hope is that patients will acquire the same immunity after their T cells are treated with zinc fingers and returned to the body.

“We are very hopeful that zinc finger technologies will have a spectacular impact on gene therapy and genetic medicine in general,” Dr. Gregory said.

Source: http://www.nytimes.com/2011/06/27/us/27therapy.html

Posted under Cell Analysis, Discoveries, Innovations and Patents, DNA Reasearch, HIV Research, North America, Research Projects, USA and Canada  |  Comments Off

Premature aging seen as issue for AIDS survivors

Last Updated on Tuesday, 14 June 2011 03:19 Written by admin Tuesday, 14 June 2011 03:19

SAN FRANCISCO (AP) — Having survived the first and worst years of the AIDS epidemic, when he was losing three friends to the disease in a day and undergoing every primitive, toxic treatment that then existed, Peter Greene is grateful to be alive.

But a quarter-century after his own diagnosis, the former Mr. Gay Colorado, now 56, wrestles with vision impairment, bone density loss and other debilitating health problems he once assumed he wouldn’t grow old enough to see.

“I survived all the big things, but now there is a new host of things. Liver problems. Kidney disease. It’s like you are a 50-year-old in an 80-year-old body,” Greene, a San Francisco travel agent, said. “I’m just afraid that this is not, regardless of what my non-HIV positive friends say, the typical aging process.”

Even when AIDS still was almost always fatal, researchers predicted that people infected with HIV would be more prone to the cancers, neurological disorders and heart conditions that typically afflict the elderly. Thirty years after the first diagnoses, doctors are seeing these and other unanticipated signs of premature or “accelerated” aging in some long-term survivors.

Government-funded scientists are working to tease apart whether the memory loss, arthritis, renal failure and high blood pressure showing up in patients in their 40s and 50s are consequences of HIV, the drugs used to treat it or a cruel combination of both. With people over 50 expected to make up a majority of U.S. residents infected with the virus by 2015, there’s some urgency to unraveling the “complex treatment challenges” HIV poses to older Americans, according to the National Institutes of Health.

“In those with long-term HIV infection, the persistent activation of immune cells by the virus likely increases the susceptibility of these individuals to inflammation-induced diseases and diminishes their capacity to fight certain diseases,” the federal health agency’s chiefs of infectious diseases, aging and AIDS research wrote, summing up the current state of knowledge on last September’s National HIV/AIDS and Aging Awareness Day. “Coupled with the aging process, the extended exposure of these adults to both HIV and antiretroviral drugs appears to increase their risk of illness and death from cardiovascular, bone, kidney, liver and lung disease, as well as many cancers not associated directly with HIV infection.”

In San Francisco, where already more than half of the 9,734 AIDS cases are in people 50 and over, University of California, San Francisco AIDS specialists are collaborating with geriatricians, pharmacists and nutritionists to develop treatment guidelines designed to help veterans of the disease cope with getting frail a decade or two ahead of schedule and to remain independent for as long as possible.

“Wouldn’t it be helpful to be able to say, are you at high risk, low risk or moderate risk for progressing to dependency in the next five, the next 10 years, being less mobile, less able to be functional in the workplace. Are you going to be safe in your home, are you going to remember to take all those medications? How are they going to interact?” explained Dr. Malcolm John, who directs UCSF’s HIV clinic. “All those questions need to be brought into the HIV field at a younger age.”

Research so far suggests that HIV is not directly causing conditions that mimic old age, but hastens patients toward ailments to which they may have been genetically or environmentally predisposed. Plus, their immune systems are being weakened over time even when they are being successfully treated for AIDS, John said.

“That’s probably true for a lot of these things. We aren’t saying HIV’s starting the problem, but it’s added fuel on top,” he said.

Stokes, a patient of John’s who goes by only his last name, is a prime example. At 53, HIV-positive since 1985 and in substance abuse recovery for the last 11 years, he says he is happier than he ever has been. Yet the number of ailments for which he is being treated would be more commonly found in someone 30 years his senior: a condition called Ramsay Hunt syndrome that causes facial paralysis, a rare cartilage disorder for which he has undergone four ear surgeries, bone death in the hip and shoulder, deterioration of his heart muscle, osteoporosis and memory loss.

A specialist recently diagnosed a Kaposi’s sarcoma spot on Stokes’ ankle. Although the cancer is not life-threatening, the sight of young men disfigured by KS lesions was a harbinger of the early AIDS crisis, and its presence on his own body is unsettling.

At his therapy group for men with HIV, aging “comes up frequently,” he said. “I say, ‘Just think what we have come through to have a life today.’” At the same time, he acknowledges sometimes feeling self-conscious about his physical appearance and worries if “people are not attracted to me and unwilling to go the length of what it means to be with me, no matter how brilliant my mind or my zest for life.”

Loneliness, financial worries and concerns about who will care for them and where can weigh on long-term AIDS survivors in the same way as all adults living in a society that values youth, Charles Emlet, a social work professor at the University of Washington, Tacoma, said.

As they get older and sicker, many feel “doubly stigmatized,” he said. Some people who have lived with the virus for a long time have been getting by on private disability benefits that will run out when they turn 65, forcing them to move to less expensive locations or to consider turning to estranged family members. Like soldiers from a distant war, many lost partners and their closest friends to AIDS.

Such emotional side effects, combined with the physical toll of managing chronic health problems, put older AIDS patients at risk for depression. At the same time, Emlet has uncovered evidence that a majority of long-term survivors also share another trait that typically comes with advanced age: that is, the ability to draw strength from their difficult experiences.

“The older adults I’ve interviewed, many of them talk about how much it means to them to give back, to do something positive with the years they never expected to have,” he said.

Peter Greene can relate to that. At times, like the days he is so exhausted he can’t get out of bed or the pain from his multiple maladies is too intense, he asks himself “the Carrie Bradshaw question–are we really lucky to still be alive?”

As frightening and uncertain as this phase of AIDS is, he thinks he knows the answer.

“I’ve tried to make the time I have count, and really, now that I have the body of an 80-year-old, I probably have the wisdom of an 80-year-old as well, which counts for a lot,” Greene said. “Everything becomes clear at the end of your life and in some ways, thinking you’ve been dying all these years, you get moments of clarity that I don’t think everyone gets.”

Source: http://www.google.com/hostednews/ap/article/ALeqM5jSFCmOu9Y714ci26I_SOCRQvDDSQ?docId=ad4d0382cdcf430c8e325be4dd84d540

Posted under Discoveries, Innovations and Patents, HIV Research, Reports  |  Comments Off

FDA Okays New HIV Drug

Last Updated on Friday, 20 May 2011 01:56 Written by admin Friday, 20 May 2011 01:56

WASHINGTON — The FDA has approved rilpivirine (Edurant) for the treatment of HIV patients who have not yet begun therapy.

The drug, a non-nucleoside reverse transcriptase inhibitor, is intended to be used as part of highly active anti-retroviral therapy (HAART) with at least two other medications, the agency said.

Rilpivirine, also known as TMC278, is to be taken once a day with food and offers another medication alternative for physicians and patients, the FDA said in a release.

The agency approved the drug on the basis of safety and effectiveness data from two phase III clinical trials with 1,368 adult participants who had not received prior HIV therapy, as well as an extension trial.

They were randomly assigned to treatment with rilpivirine or efavirenz (Sustiva), as well as other anti-HIV drugs.

In the two trials, the proportion of patients who were able to suppress their virus to undetectable levels was 84.3% for rilpivirine and 82.3% for efavirenz.

Those who started the trials with a high viral load and were assigned to rilpivirine were more likely to fail therapy than those who got efavirenz and the converse was true for those who started with a low level of virus, the researchers reported.

On the other hand, patients were more likely to drop out because of side effects if they were taking efavirenz, leading some observers to call the medication a trade-off.

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Trana Discovery’s HIV Assay Finds Compounds that Inhibit NNRTI and Multi-Drug Resistant HIV Viruses

Last Updated on Wednesday, 15 December 2010 10:20 Written by Editor Wednesday, 15 December 2010 10:20

Trana Discovery, Inc., an infectious disease drug discovery technology company, today announced that a recent study sponsored by the National Institute of Allergy and Infectious Disease, part of the National Institutes of Health, affirms that bioactive compounds selected using the Trana HIV 201 High-Throughput (HTS) Assay inhibit viral strains demonstrating resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). The results of the in vitro testing indicate that the selected compounds do not appear to act as NNRTIs, but rather by a different mechanism of action. In addition, these compounds were found to modestly inhibit a multi-drug resistant virus that has demonstrated resistance to commonly prescribed HIV treatments such as nevirapine, saquinavir, 3TC and AZT.

The Trana HIV assay is based on the premise that HIV has evolved to use tRNALys3 as a primer for initiation of reverse transcription. The tRNALys3 primer is required to copy its genetic material and generate new viruses. Therefore, the interaction between tRNALys3 and viral genomic RNA represents a potential novel target for HIV drug development. The Trana HIV assay is designed to select compounds that inhibit the use of tRNALys3 by HIV and that in turn can be developed as new anti-HIV drug therapies.

Through a collaboration with Southern Research Institute, the HIV assay was deployed in three separate screening campaigns against more than 120,000 diverse compounds. Seven bioactive compounds were selected for additional follow-up testing and characterization in dose-response against NNRTI-resistant HIV isolates in peripheral blood mononuclear cell (PBMC) assays. These seven compounds were previously found to have modest antiviral activity against HIV in a cell-based assay.

Testing against NNRTI-resistant viruses was conducted to study whether or not the compounds were acting as NNRTIs. The results from this testing indicated there was no apparent difference in antiviral activity based on the presence of NNRTI-resistance mutations in the viruses, which indicates the compounds don’t appear to act as NNRTIs.

“These results help to demonstrate that the Trana HIV assay identifies compounds that act through a different mechanism of action,” said Steve Peterson, CEO of Trana Discovery. “Trana has filed for patent protection on these compounds as well as their ability to inhibit HIV-resistant isolates. We are now in a position to license the HIV assay, drug class and bioactive compounds to qualified pharmaceutical companies for further development.”

High-throughput screening of an additional 200,000 compounds using the Trana HIV 201 HTS Assay has recently been completed. Compounds found to be active as a result of this additional screening are currently being identified for similar follow-up testing against HIV replication in cell-based assays. Based on prior experience, similar results are anticipated.

High-throughput screening using the Trana HIV 201 HTS Assay and follow-up testing of compounds for bioactivity against HIV in cell-based assays was performed under the NIAID, DAIDS contract N01-AI-70042; Roger Miller, Project Officer. In addition, testing of the compounds against NNRTI and multi-drug resistant HIV in PBMCs was supported by the NIAID, DAIDS contract N01-AI-70041; Steven Turk, Project Officer.

Source: prlog.org ; TRANA Discovery

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AIDS Drugs – HIV

Last Updated on Monday, 14 December 2009 05:19 Written by Editor Monday, 14 December 2009 05:19

In the early 1980s, the human immunodeficiency virus (HIV) was identi­fied as the etiologic agent of acquired immune deficiency syndrome (AIDS). More than 3 million people worldwide died from HIV/AIDS in 2003, according to a July 2004 United Nations report. During the same period, about 5 million people contracted the human immunodeficiency virus, bringing the total number of people living with HIV worldwide to 38 million. Although AIDS was called the «gay men’s disease» at the be­ginning of the outbreak, it was soon discovered that sexual intercourse was not the only way of transmission. Blood transfusions and mother-to-baby transmission also spread the virus.

In comparison to the scourges caused by other viruses in history, we were more prepared and have achieved astonishing milestones against AIDS, thanks to our accumulated knowledge and efforts around the globe. HIV was identified and shown to be the cause of AIDS in less than 2% years. It took only another 2 years for blood tests to become commercially available. In 1987, the first anti-HIV drug, AZT, was introduced. With the arrival of the HIV protease inhibitors and triple drug therapy (the cocktail therapy) in 1995, many patients who would otherwise have died are still alive. In 1996, Time magazine named AIDS researcher David Ho «Man of the Year» for his revolutionary idea of the cocktail therapy.

Who discovered HIV was such a contentious is­sue that it took the President of the United States and the Premier of France to settle the dispute.

In 1983 Francoise Barre-Sinoussi and Luc Montagnier, in the laboratory led by Montagnier at the Institut Pasteur de Paris, first detected and later iso­lated a retrovirus, lymphadenopathy-associated virus (LAV), which they believed was the cause of AIDS. During their research on the virus, Montagnier’s lab­oratory collaborated with Robert C. Gallo, a renowned virologist at the National Cancer Institute (NCI), who was one of the most widely referenced scientists in the world in the 1980s and 1990s. Montagnier and Gallo frequently exchanged virus sampies and information. In April 1984, Gallo held a press conference an­nouncing that his laboratory had isolated a retrovirus, human T-lym-photrophic virus (HTLV-III), that he believed to be the cause of AIDS. Gallo was basking in scientific glory and was widely considered a leading contender for the Nobel Prize. Soon it was confirmed that Gallo’s HTLV-III and Montagnier’s LAV were identical. In 1986, a nomenclature com­mittee was set up, chaired by Harold Varmus, an expert in avian retrovirus and then director of the NIH. The NIH committee settled on the name of human immunodeficiency virus (HIV).

In April 1984, Gallo’s laboratory filed a patent on an HIV blood test kit using his HTLV-IIIB-ELISA (enzyme-linked immunosorbent assay), which was issued in a record 13 months via a special category involving na­tional security. Although Institut Pasteur had filed a patent in the United States much earlier, in December 1983, it was not granted until a later date. Gallo’s HIV test kit was approved by the FDA in 1985. An acrimonious le­gal battle ensued for the priority of the discovery of the HIV between the French and American teams. The contentious scientific and legal contro­versies came to an end in March 1987 when a historic agreement was signed by the directors of the NIH and the Institut Pasteur and ratified by Ronald Reagan and Jacques Chirac. The patents would become the joint properties of the two institutions, which would share the royalties. The three inventors from the NIH, including Gallo, would receive $100,000 annually from the royalties earned.

Even the intervention by two heads of state did not put the matter to rest. In November 1989, a Pulitzer Prize-winning investigative reporter, John Crewdson, published a 50,000-word article in the Chicago Tribune on the Montagnier-Gallo priority dispute. He concluded that Gallo had either stolen or allowed his samples to be contaminated with Montagnier’s virus. The controversy generated resulted in congressional investigations. In the end, it was found that Mikulas (Mika) Popovic from Czechoslovak­ia, a cell biologist in Gallo’s laboratory, had isolated HTLV-III from a pool by mixing several blood samples from different sources, including Montagnier’s sample, which contained LAV. Pooling blood samples was an unusual practice in virology. In 1991, Gallo admitted in Nature that he had not discovered the new virus. In 1996, he left the NCI, where he had worked for 30 years, to become the director of the Institute of Hu­man Virology at the University of Maryland Biotechnology Institute in Baltimore.

In 1987, the first anti-AIDS drug, AZT, was introduced by Burroughs Wellcome. AZT, which blocks HIV reverse transcriptase activity, stands for azidothymidine, with the generic name of zidovudine and the trade name of Retrovir. Popular media often give the credit to Gertrude Elion of Burroughs Wellcome for having discovered AZT. In fact, al­though Elion and George Hitchings (see chapter 1, page 19) developed the concept of using nucleotides as antimetabolites in treating cancers, AZT itself was synthesized by a group led by Jerome Horowitz of the Detroit Institute of Cancer Research in 1964 as a possible anticancer drug. Horowitz, now a professor at Wayne State University, published his syn­thesis as a note in the. Journal of Organic Chemistry in 1964.

Since its birth, AZT had a checkered life as a drug looking for a disease to treat. AZT did not show efficacy in treating cancers; the drug also failed to prolong the lives of leukemic animals. In 1974, a German laboratory found it effective against viral infection in mice—Wolfram Ostertag of the Max Planck Institute for Experimental Medicine showed that leukemia helper virus (LLV-F) replication by AZT occurred via phosphorylation of AZT to the corresponding triphosphate, which cannot be incorporated into the growing strand of DNA. Ostertag correctly concluded that AZT-triphosphate worked by binding to the growing strand of DNA. Bur­roughs Wellcome acquired AZT and explored the possibility of using it to treat the herpes virus under the guidance of Gertrude Elion, although it did not make it to the market.