Mystery of the HIV Cure trial?

Mystery of the HIV Cure trial?

Mystery of the HIV Cure trial?

**Before you proceed the company which initially started the trial went bankrupt and most of the records have been lost, except the trial participants which have all been followed since 2003.

A special issue on progress toward a cure for HIV includes a description of a previously unreported study started in the early 2000s that describes AIDS patients currently ages 51-67 in good health. These nine individuals were treated with a unique formula of traditional Chinese herbal medicine (TCM) from 2001-2006 or longer, with or without occasional antiviral therapy added later. The fact that the patients currently have low or undetectable HIV in their systems is unexpected and intriguing, and suggests a potential promise of TCM as a functional cure for HIV/AIDS, as discussed in a Letter to the Editor in the special issue of AIDS Research and Human Retroviruses, FEB 2017

Citation: Long-Term Survival of AIDS Patients Treated with Only Traditional Chinese Medicine
AIDS Res Hum Retroviruses. 2017 Feb 1; 33(2): 90–92. Published online 2017 Feb 1. doi:  10.1089/aid.2016.0288

Herpes Virus Cleared from Cells BX795

Herpes Virus Cleared from Cells BX795

Herpes Virus Cleared from Cells BX795

From a completely accidental discovery: “BX795 is known as an inhibitor of TBK1, an enzyme involved in innate immunity and neuroinflammation. When TBK1 is suppressed in cells, infection is actually promoted. But when the researchers added higher concentrations of BX795 to cultured human corneal cells infected with HSV-1, the infection was quickly cleared.”

Citation: An off-target effect of BX795 blocks herpes simplex virus type 1 infection of the eye. Science Translational Medicine, 2018; 10 (428): eaan5861 DOI: 10.1126/scitranslmed.aan5861

Proposed federal legislation targets 32 US states that retain laws making it illegal to not declare HIV status to sexual partners

New bill seeks to repeal outdated state HIV discrimination laws

Dan Roberts in Washington

theguardian.com,     Tuesday 10 December 2013 15.48 EST

South Africans protest in support of action on HIV and Aids
ProPublica’s study ound 541 cases over the last decade where people have been convicted of, or pleaded guilty to, criminal charges for not disclosing their HIV status. Photo: Nic Bothma/EPA

A campaign against the criminalisation of HIV infection received a boost on Tuesday with the introduction of a bill in the US Senate aimed at repealing state laws said to discriminate against people with the virus.

Senator Chris Coons of Delaware joined existing efforts in the House of Representative by sponsoring legislation to roll back laws regulating the sexual activity of HIV-positive patients, many of which were introduced during initial waves of Aids panic in the 1980s.

His proposed federal legislation is targeted at 32 US states that retain laws making it illegal to not declare HIV status to sexual partners, regardless of whether there is a risk of transmission. Thirteen of these states also criminalise non-sexual acts, such as spitting, even though transmission by saliva is now thought impossible in such cases.

Coons, a member of the Senate judiciary committee, said such policies unfairly stigmatise the disease by applying differing legal standards for people with HIV, who can still be prosecuted for deliberate transmission of the virus under other criminal laws.

“It’s simply not fair that someone having been diagnosed with a chronic, treatable medical condition should automatically be subject to a different set of criminal laws,” he said.

“A disturbing number of state and local criminal laws pertaining to individuals with HIV/Aids are rooted not in science, but outdated fear. Rather than recognising that HIV/Aids is a treatable medical condition, these laws perpetuate the idea that HIV is a deadly weapon and people with HIV/Aids are dangerous criminals.”

His bill, known as the Repeal Existing Policies that Encourage and Allow Legal HIV Discrimination Act, mirrors a similar attempt to modernise state law in the House of Representatives.

Read More: http://www.theguardian.com/world/2013/dec/10/us-house-hiv-bill-discrimination

Proposed federal legislation targets 32 US states that retain laws making it illegal to not declare HIV status to sexual partners

New bill seeks to repeal outdated state HIV discrimination laws

Dan Roberts in Washington

theguardian.com,     Tuesday 10 December 2013 15.48 EST

South Africans protest in support of action on HIV and Aids
ProPublica’s study ound 541 cases over the last decade where people have been convicted of, or pleaded guilty to, criminal charges for not disclosing their HIV status. Photo: Nic Bothma/EPA

A campaign against the criminalisation of HIV infection received a boost on Tuesday with the introduction of a bill in the US Senate aimed at repealing state laws said to discriminate against people with the virus.

Senator Chris Coons of Delaware joined existing efforts in the House of Representative by sponsoring legislation to roll back laws regulating the sexual activity of HIV-positive patients, many of which were introduced during initial waves of Aids panic in the 1980s.

His proposed federal legislation is targeted at 32 US states that retain laws making it illegal to not declare HIV status to sexual partners, regardless of whether there is a risk of transmission. Thirteen of these states also criminalise non-sexual acts, such as spitting, even though transmission by saliva is now thought impossible in such cases.

Coons, a member of the Senate judiciary committee, said such policies unfairly stigmatise the disease by applying differing legal standards for people with HIV, who can still be prosecuted for deliberate transmission of the virus under other criminal laws.

“It’s simply not fair that someone having been diagnosed with a chronic, treatable medical condition should automatically be subject to a different set of criminal laws,” he said.

Continue reading “Proposed federal legislation targets 32 US states that retain laws making it illegal to not declare HIV status to sexual partners”

Micronutrient supplements reduce risk of HIV disease progression and illness

Contact: Maydel Santana-Bravo santanam@fiu.edu 305-348-1555 The JAMA Network Journals

Long-term (24-month) supplementation with multivitamins plus selenium for human immunodeficiency virus (HIV)-infected patients in Botswana in the early stages of disease who had not received antiretroviral therapy delayed time to HIV disease progression, was safe and reduced the risk of immune decline and illness, according to a study appearing in the November 27 issue of JAMA.

“Micronutrient deficiencies, known to influence immune function, are prevalent even before the development of symptoms of HIV disease and are associated with accelerated HIV disease progression. Micronutrient supplementation has improved markers of HIV disease progression (CD4 cell count, HIV viral load) and mortality in clinical trials; however, these studies were conducted either in the late stages of HIV disease or in pregnant women,” according to background information in the article.

Marianna K. Baum, Ph.D., of Florida International University, Miami, and colleagues examined whether specific supplemental micronutrients enhance the immune system and slow HIV disease progression during the early stages of the disease in antiretroviral therapy (ART)-naive adults. They randomized 878 HIV patients to supplementation with daily multivitamins (B vitamins and vitamins C and E), selenium alone, multivitamins with selenium, or placebo for 24 months. The vitamins (vitamins B, C and E, and the trace element selenium) are nutrients essential for maintaining a responsive immune system. Selenium may also have an important role in preventing HIV replication.

Participants receiving the combined supplement of multivitamins plus selenium had a lower risk compared to placebo of reaching a CD4 cell count 250/µL or less (a measure that is consistent with the standard of care in Botswana for initiation of ART at the time of the study). This supplement also reduced the risk of a combination of measures of disease progression (CD4 cell count ≤ 250/µL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier).

“This evidence supports the use of specific micronutrient supplementation as an effective intervention in HIV-infected adults in early stages of HIV disease, significantly reducing the risk for disease progression in asymptomatic, ART-naive, HIV-infected adults. This reduced risk may translate into delay in the time when the HIV-infected patients experience immune dysfunction and into broader access to HIV treatment in developing countries,” the authors conclude.

The researchers add that their “findings are generalizable to other HIV subtype C-infected cohorts in resource-limited settings where the provision of ART is being scaled up, rolled out, or not yet available to all in conditions similar to those in Botswana at the time of this study.”

###

(doi:10.l001/jama.2013.280923; Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This study was funded by the National Institute on Drug Abuse. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported

New and more virulent strain of HIV is spreading rapidly through Russia, claim scientists

  • The HIV subtype 02_AG/A  is spreading rapidly and is now thought to account for more than 50 per cent of  new HIV infections in Siberia
  • It is thought to be the most virulent  subtype of the virus in Russia
  • Infections have also been reported in  Chechnya, Kyrgyzstan and Kazakhstan

By  Emma Innes

PUBLISHED: 06:42 EST, 17  October 2013 |  UPDATED: 06:51 EST, 17 October 2013

Russian scientists believe they have  identified a new and more virulent strain of HIV.

The subtype, known as 02_AG/A, is spreading  rapidly and is now thought to account for more than 50 per cent of new HIV  infections in Siberia.

The virus was first seen in the city of  Novosibirsk in 2006 and is thought to be the most virulent subtype of the virus  in Russia.

Russian scientists believe they have identified a new and more virulent strain of HIV. The subtype, known as 02_AG/A, is spreading rapidly. Image shows mature HIV virus infection 

Russian scientists believe they have identified a new  and more virulent strain of HIV. The subtype, known as 02_AG/A, is spreading  rapidly. Image shows mature HIV virus infection

 

It was discovered by scientists at the State  Research Center of Virology and Biotechnology VECTOR in Siberia, The Moscow News reports.

Natalya Gashnikova, head of the retroviruses  department at Vektor, said 02_AG/A could spread through the population much more  quickly than the current main HIV strain found in Russia.

The number of HIV positive people in  Novosibirsk has jumped from 2,000 in 2007 to 15,000 in 2012, according to  Russia’s Federal AIDS Centre and 50 per cent of the new cases have been caused  by 02_AG/A.

The newly identified subtype is not confined  to Siberia – cases have also been reported in Chechnya, in the south of Russia,  and Kyrgyzstan and Kazakhstan.

HIV can be divided into two main types –  HIV-1 and HIV-2. HIV-1 is the more virulent of the two and is, therefore,  responsible for the majority of cases.

HIV-1 can also be divided into subgroups and  the newly discovered 02_AG/A is a subgroup of HIV-1.

All of the subgroups are transmitted from  person to person through the same transmission methods – including unprotected  sex and sharing needles – but some are easier to pass on than others.

02_AG/A is thought to be easier to transmit  than some other subtypes.

The virus was first seen in the city of Novosibirsk in 2006 and is thought to be the most virulent subtype of the virus in Russia 

The virus was first seen in the city of Novosibirsk in  2006 and is thought to be the most virulent subtype of the virus in Russia. It  is now thought to account for more than 50 per cent of new HIV infections in  Siberia

 

UN figures show that the only regions where  the number of HIV infections is increasing are Eastern Europe and Central Asia –  52 per cent of people with HIV in this area live in  Russia.

This is  believed to be partly because there  is little awareness of HIV in many  parts of Russia and because Russian school  offer very little sex  education.

The number  of new HIV infections globally  has plummeted by a third since 2001 and  more than halved among children, the  United Nations recently revealed.

Globally, 2.3 million people contracted the  AIDS virus last year – down 33 per  cent from 2001, while 260,000 children  became infected – 52 per cent  less than in 2001.

‘The annual number of new HIV infections  continues to decline with especially sharp reductions in the number of children  newly infected with HIV,’ UNAIDS executive director Michel Sidibe  said.

Last year, 1.6 million people died of  AIDS-related deaths, down from 1.8 million in 2011 and 2.3 million in  2005.

The report showed that 9.7 million people in  low and middle-income countries, the bulk of those infected, had access to HIV  drugs last year, compared to only 1.3 million seven years  earlier.

While the hike is impressive, it falls short  of a UN target announced two years ago to reach 15 million people by  2015.

Some 35.3 million people were living with the  virus last year – about 70 per cent of them in sub-Saharan Africa – up from 30  million in 2001.

Read more: http://www.dailymail.co.uk/health/article-2464403/New-virulent-strain-HIV-spreading-rapidly-Russia-claim-scientists.html#ixzz2hzqsBz5g Follow us: @MailOnline on Twitter | DailyMail on Facebook

Disarming HIV With a “Pop”

PHILADELPHIA,          September 19, 2013

The DAVEI molecule is comprised of two main pieces: Membrane Proximal External Region (MPER), which attaches to the viral membranes, and cyanovarin (CVN), which binds to the sugar coating of the virus’s protein spike.

Pinning down an effective way to combat the spread of the human immunodeficiency virus, the viral precursor to AIDS, has long been a challenge for scientists and physicians, because the virus is an elusive one that mutates frequently and, as a result, quickly becomes immune to medication. A team of Drexel University researchers is trying to get one step ahead of the virus with a microbicide they’ve created that can trick HIV into “popping” itself into oblivion.

Its name is DAVEI – which stands for “Dual Action Virolytic Entry Inhibitor”- and it can pull a fast one on HIV. DAVEI was invented and tested by scientists from Drexel’s College of Engineering; School of Biomedical Engineering, Science and Health Systems; and College of Medicine, and is the latest in a new generation of HIV treatments that function by specifically destroying the virus without harming healthy cells.

“While several molecules that destroy HIV have recently been announced, DAVEI is unique among them by virtue of its design, specificity and high potency,” said Dr. Cameron Abrams, a professor in Drexel’s College of Engineering and a primary investigator of the project.

A team co-led by Abrams and Dr. Irwin Chaiken in the Department of Biochemistry and Molecular Biology in Drexel’s College of Medicine, and including Dr. Mark Contarino and doctoral students Arangassery Rosemary Bastian and R. V. Kalyana Sundaram, developed the chimeric recombinantly engineered protein – that is, a molecule assembled from pieces of other molecules and engineered for a specific purpose, in this case to fight HIV. Their research will be published in the October edition of the American Society for Microbiology’s Antimicrobial Agents and Chemotherapy.

The idea behind DAVEI was to design a molecule that hijacks the virus’s fusion machinery, the tools it uses to attach to and attack a healthy cell, and tricks the virus into destroying itself. HIV invades a healthy cell by first attaching via protein “spikes” that then collapse to pull viral and cell membranes together, fusing them and allowing the genetic contents of the virus to enter the healthy cell. The cell is rewired by the viral genetic material into producing more viruses instead of performing its normal function, which, in the case of cells infected by HIV, involves normal immunity. AIDS is the result.

“We hypothesized that an important role of the fusion machinery is to open the viral membrane when triggered, and it follows that a trigger didn’t necessarily have to be a doomed cell,” Abrams said. “So we envisioned particular ways the components of the viral fusion machinery work and designed a molecule that would trigger it prematurely,” Abrams said.

The team designed DAVEI from two main ingredients. One piece, called the Membrane Proximal External Region (MPER), is itself a small piece of the fusion machinery and interacts strongly with viral membranes. The other piece, called cyanovirin, binds to the sugar coating of the protein spike. Working together, the MPER and cyanovirin in DAVEI “tweak” the fusion machinery in a way that mimics the forces it feels when attached to a cell.

“For lack of a better term, DAVEI ‘tricks’ the virus into ‘thinking’ it is about to infect a healthy cell, when, in fact, there is nothing there for it to infect,” Abrams said. “Instead, it releases its genetic payload harmlessly and dies.”

Chaiken’s lab has extensively studied the molecular mechanisms of HIV-1 envelope protein interactions and structure-based design of agents that fight HIV. The researchers produced DAVEI using recombinant protein engineering and used HIV-1 pseudoviruses to demonstrate that it can physically rupture and irreversibly inactivate the virus particles.

“DAVEI and other new-generation virolytic inactivators open up an important opportunity to develop a topical microbicide to block the transmission of HIV, and at the same time provide lead ideas to discover treatment strategies for people who are already infected,” Chaiken said. “Our hope is that determining the structural driving forces of both inhibitors and viral entry machinery that enable spike inactivation will help to advance molecular designs with increased power, specificity and clinical potential for both prevention and treatment.”

 

News Media Contact

Britt Faulstick

News Officer, University Communications

britt.faulstick@drexel.edu Phone: 215-895-2617 Mobile: 215-796-5161

Ed Federico

Media Relations Manager, Drexel University College of Medicine

edward.federico@drexelmed.edu Phone: 215-255-7331

– See more at: http://drexel.edu/now/news-media/releases/archive/2013/September/DAVEI-HIV-molecule/#sthash.7eofB5q4.dpuf

Designer Molecule Causes AIDS Virus to Destroy Itself

A scanning electron micrograph shows HIV particles infecting a colorized human H9 T cell. (Credit: NIAID) FILE PHOTO

A scanning electron micrograph shows HIV particles infecting a colorized human H9 T cell. (Credit: NIAID) FILE PHOTO

by Jessica Berman

Researchers have designed a synthetic molecule that tricks the AIDS virus into destroying itself. The compound, called DAVEI, was developed by researchers at Philadelphia’s Drexel University and causes the deadly pathogen to eject its contents before it can infect human cells.

The AIDS virus uses protein spikes on its surface to fuse to healthy cells. Once attached, the microbe inserts its genetic material, turning the cells into little factories that crank out thousands of copies of HIV.

But DAVEI hijacks the virus, mimicking its interaction with immune system cells. DAVEI binds to the pathogen’s outer coat, triggering a firing mechanism that breaches the wall of the AIDS virus, according to Irwin Chaiken, a researcher in the Department of Biochemistry and Molecular Biology at Drexel’s College of Medicine.

Explaining how DAVEI works, Chaiken said, “so that the contents that are inside the virus that are small enough to go through the pores will go through the pores and leak out. And at that point, the virus shrinks and it becomes inactivated.”

DAVEI was designed by Cameron Abrams, a professor of engineering at Drexel. Abrams envisions using the synthetic agent in a microbicide, a cream or gel that women can use vaginally to protect themselves from contracting the disease from their HIV-infected partners.

“And so this we think this would benefit primarily populations in sub-Saharan Africa where male-to-female transmission is very high rate, young women are being infected at a very high rate. That’s extremely detrimental to those societies,” said Abrams.

Abrams also says DAVEI might be used someday as a treatment for those who are HIV positive by destroying infected cells.

“In an active infection in an individual, there are cells that are continuously producing virus. And if those cells could be destroyed before they produce a lot of virus that obviously would be very good,” Abrams pointed out.

Researchers say much more work needs to be done with DAVEI and compounds like it before actual anti-HIV therapies could be developed. An article on the manmade molecule was published in the October edition of Antimicrobial Agents and Chemotherapy.

 

http://www.voanews.com/content/designer-molecule-causes-aids-virus-destroy-itself/1753479.html

Large HIV study stopped after safety review found more study participants who received the vaccine later became infected

HIV vaccine study halted by US government over unsuccessful shots

Associated Press in Washington

guardian.co.uk,  Thursday 25 April 2013 17.52 EDT

A pharmaceutical machine loaded with ARV medicine at the Themba Lethu HIV/Aids clinic, Johannesburg

A 2009 study in Thailand is the only HIV/Aids study ever to show a modest success. Photograph: Denis Farrell/AP

The US government halted a large HIV vaccine study on Thursday, saying the experimental shots were not successful in preventing infection.

Nor did the shots reduce the amount of the Aids virus in the blood when people who had been vaccinated later became infected, the National Institutes of Health said.

“It’s disappointing,” said Dr Anthony Fauci, head of NIH’s National Institute of Allergy and Infectious Diseases. But he said there was “important information” gained from the study that will help determine what to try next.

The study had enrolled 2,504 volunteers, mostly gay men, in 19 cities since 2009. Half received dummy shots, and half received a two-part experimental vaccine developed by the NIH. All were provided free condoms and given extensive counseling about the risks of HIV.

It’s a strategy known as “prime-boost”. A DNA-based vaccine made with genetically engineered HIV material is given to prime the immune system to attack the Aids virus. Then a different vaccine, encasing the same material inside a shell made of a disabled cold virus, acts as a booster shot to strengthen that response. Neither vaccine could cause HIV.

The idea was to train immune cells known as T cells to spot and attack the very earliest HIV-infected cells in someone’s body. The hope was that the vaccine could either prevent HIV infection, or help those infected anyway to fight it.

A safety review this week found that slightly more study participants who had received the vaccine later became infected with HIV. It’s not clear why. But the difference wasn’t statistically significant, meaning it may be due to chance. Overall, there were 41 HIV infections in the vaccinated group and 30 among placebo recipients. When researchers examined only participants diagnosed after being in the study for at least 28 weeks – long enough for the shots to have done their job – there were 27 HIV infections among the vaccinated and 21 among the placebo recipients.

The NIH said Thursday that it is stopping vaccinations in the study, known as HVTN 505, but that researchers will continue to study the volunteers’ health.

Josh Robbins, 30, of Nashville, Tennessee, was one of the participants who became infected with HIV. He said he was glad he had taken part because its close monitoring meant he was diagnosed and treated much sooner than most people.

“We’ve got to keep moving forward,” Robbins said. The study “certainly can lead us down a new direction to hopefully find something that might work.”

Multiple attempts at creating an Aids vaccine have failed over the years. A 2009 study in Thailand is the only one ever to show a modest success, using a somewhat different prime-boost approach. Newer research suggests another approach – to try creating powerful antibodies that could work a step earlier than the T-cell attack, before HIV gets inside the first cell.

Both approaches need continued research funding, said Mitchell Warren of the international Aids Vaccine Advocacy Coalition.  “Clearly an Aids vaccine remains critical,” he said.

http://www.guardian.co.uk/society/2013/apr/25/hiv-aids-vaccine-study-us-government

 

Study: Widespread ‘test-and-treat’ HIV policies could increase dangerous drug resistance

Contact: Robert Perkins perkinsr@usc.edu 213-740-9226 University of Southern California

Testing helps catch the disease early, but experts caution that aggressive use of antiretroviral drugs in asymptomatic patients could breed more resistant HIV

One of the most widely advocated strategies for dealing with HIV/AIDS could double the number of multi-drug-resistant HIV cases in the population of men who have sex with men (MSM) in LA County over the next 10 years, cautions a new study.

In the United States, LA County has the largest incident population of HIV positive individuals.

The so-called “test and treat” policy — which calls for universal testing for HIV as well as treatment with antiretroviral drugs for even those at the earliest stages of the disease — is popular because it has been shown to decrease the number of new HIV cases and deaths due to AIDS.

The problem, according to the study, is that such aggressive and widespread use of antiretroviral drugs would also rapidly and dramatically increase the prevalence of multiple-drug-resistant HIV (MDR).

“We’re not saying that testing everybody and treating everybody is bad. All we’re saying is that you should proceed with caution and closely monitor the prevalence of multi-drug-resistant HIV as you scale up the test and treat model,” said lead author Neeraj Sood, associate professor at the USC Schaeffer Center for Health Policy and Economics.

Sood collaborated with Zachary Wagner, also of the USC Schaeffer Center; USC Ph.D. student Emmanuel Drabo; and Raffaele Vardavas and Amber Jaycocks of the RAND Corporation. Their study received advance online publication by Clinical Infectious Diseases on March 13.

Sood and his colleagues studied the MSM population in LA County, which accounts for 82 percent of people living with HIV/AIDS countywide. They tracked how the disease was treated from 2000 to 2009 and how the virus responded.

Using data from the Centers for Disease Control and their own data, the researchers then generated a model of how the disease would respond under a more aggressive “test and treat” policy over the next 10 years.

The model showed the prevalence of MDR jumping from 4.79 percent to 9.06 percent by 2023.

A more cautious approach, Sood suggested, would be simply to aggressively test for the disease but to avoid prescribing antiretroviral drugs to asymptomatic patients. The modeling shows that strategy still making significant gains against HIV/AIDS, without the increase in MDR HIV.

“Prior studies show a dramatic reduction in risk-taking behavior by individuals once they know their HIV-positive status,” Sood said.

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This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, grant # R01HD054877.

More HIV ‘cured’: first a baby, now 14 adults

 

A drug-free life beckons for some people with HIV <i>(Image: Bruce Forster/Getty)</i>A drug-free life beckons for some people with HIV (Image: Bruce Forster/Getty)

Two weeks after the revelation that a baby has been “cured” of HIV, reports suggest that a similar treatment can cure some adults too. Early treatment seems crucial, but does not guarantee success.

Asier Sáez-Cirión of the Pasteur Institute’s unit for regulation of retroviral infections in Paris analysed 70 people with HIV who had been treated with antiretroviral drugs (ARVs) between 35 days and 10 weeks after infection – much sooner than people are normally treated.

All of the participants’ drug regimes had been interrupted for one reason or another. For example, some people had made a personal choice to stop taking the drugs, others had been part of a trial of different drug protocols.

Most of the 70 people relapsed when their treatment was interrupted, with the virus rebounding rapidly to pre-treatment levels. But 14 of them – four women and 10 men – were able to stay off of ARVs without relapsing, having taken the drugs for an average of three years.

The 14 adults still have traces of HIV in their blood, but at such low levels that their body can naturally keep it in check without drugs.

Drugless years

On average, the 14 adults have been off medication for seven years. One has gone 10-and-a-half years without drugs. “It’s not eradication, but they can clearly live without pills for a very long period of time,” says Sáez-Cirión.

Last week, a baby was reported to have been “functionally cured” of HIV after receiving a three-drug regime of ARVs almost immediately after birth. Sáez-Cirión warns that rapid treatment doesn’t work for everyone, but the new study reinforces the conclusion that early intervention is important.

“There are three benefits to early treatment,” says Sáez-Cirión. “It limits the reservoir of HIV that can persist, limits the diversity of the virus and preserves the immune response to the virus that keeps it in check.”

Further analysis confirmed that the 14 adults were not “super-controllers” – the 1 per cent of the population that are naturally resistant to HIV – since they lack the necessary protective genes. Also, natural controllers rapidly suppress their infections, whereas these 14 mostly had severe symptoms which led to their early treatment. “Paradoxically, doing badly helped them do better later,” says Sáez-Cirión.

Rapid response

The researchers are trying to identify additional factors that could explain why early intervention only works on some people, hopefully extending the scope for more functional cures.

“This whole area is fascinating, and we’ve been looking very closely at issues of early initiation of treatment, and the potential for functional cures,” says Andrew Ball, senior adviser on HIV/AIDS strategy at the World Health Organization in Geneva.

“The big challenge is identifying people very early in their infection,” says Ball, adding that many people resist testing because of the stigma and potential discrimination. “There’s a good rationale for being tested early, and the latest results may give some encouragement to do that,” he says.

Journal reference: PLoS Pathogens, DOI: 10.1371/journal.ppat.1003211

http://www.newscientist.com/article/dn23276-more-hiv-cured-first-a-baby-now-14-adults.html

 

Nanoparticles loaded with bee venom kill HIV

 

March 7, 2013
By Julia Evangelou Strait

Joshua L. Hood, MD, PhD

Nanoparticles (purple) carrying melittin (green) fuse with HIV (small circles with spiked outer ring), destroying the virus’s protective envelope. Molecular bumpers (small red ovals) prevent the nanoparticles from harming the body’s normal cells, which are much larger in size.

Article Body 2010

Nanoparticles carrying a toxin found in bee venom can destroy human immunodeficiency virus (HIV) while leaving surrounding cells unharmed, researchers at Washington University School of Medicine in St. Louis have shown. The finding is an important step toward developing a vaginal gel that may prevent the spread of HIV, the virus that causes AIDS.

“Our hope is that in places where HIV is running rampant, people could use this gel as a preventive measure to stop the initial infection,” says Joshua L. Hood, MD, PhD, a research instructor in medicine.

The study appears in the current issue of Antiviral Therapy.

Bee venom contains a potent toxin called melittin that can poke holes in the protective envelope that surrounds HIV, and other viruses. Large amounts of free melittin can cause a lot of damage. Indeed, in addition to anti-viral therapy, the paper’s senior author, Samuel A. Wickline, MD, the J. Russell Hornsby Professor of Biomedical Sciences, has shown melittin-loaded nanoparticles to be effective in killing tumor cells.

The new study shows that melittin loaded onto these nanoparticles does not harm normal cells. That’s because Hood added protective bumpers to the nanoparticle surface. When the nanoparticles come into contact with normal cells, which are much larger in size, the particles simply bounce off. HIV, on the other hand, is even smaller than the nanoparticle, so HIV fits between the bumpers and makes contact with the surface of the nanoparticle, where the bee toxin awaits.

“Melittin on the nanoparticles fuses with the viral envelope,” Hood says. “The melittin forms little pore-like attack complexes and ruptures the envelope, stripping it off the virus.”

According to Hood, an advantage of this approach is that the nanoparticle attacks an essential part of the virus’ structure. In contrast, most anti-HIV drugs inhibit the virus’s ability to replicate. But this anti-replication strategy does nothing to stop initial infection, and some strains of the virus have found ways around these drugs and reproduce anyway.

“We are attacking an inherent physical property of HIV,” Hood says. “Theoretically, there isn’t any way for the virus to adapt to that. The virus has to have a protective coat, a double-layered membrane that covers the virus.”

Beyond prevention in the form of a vaginal gel, Hood also sees potential for using nanoparticles with melittin as therapy for existing HIV infections, especially those that are drug-resistant. The nanoparticles could be injected intravenously and, in theory, would be able to clear HIV from the blood stream.

“The basic particle that we are using in these experiments was developed many years ago as an artificial blood product,” Hood says. “It didn’t work very well for delivering oxygen, but it circulates safely in the body and gives us a nice platform that we can adapt to fight different kinds of infections.”

Since melittin attacks double-layered membranes indiscriminately, this concept is not limited to HIV. Many viruses, including hepatitis B and C, rely on the same kind of protective envelope and would be vulnerable to melittin-loaded nanoparticles.

While this particular paper does not address contraception, Hood says the gel easily could be adapted to target sperm as well as HIV. But in some cases people may only want the HIV protection.

“We also are looking at this for couples where only one of the partners has HIV, and they want to have a baby,” Hood says. “These particles by themselves are actually very safe for sperm, for the same reason they are safe for vaginal cells.”

While this work was done in cells in a laboratory environment, Hood and his colleagues say the nanoparticles are easy to manufacture in large enough quantities to supply them for future clinical trials.

 


Hood JL, Jallouck AP, Campbell N, Ratner L, Wickline SA. Cytolytic nanoparticles attenuate HIV-1 infectivity. Antiviral Therapy. Vol. 19: 95 – 103. 2013

This work was supported by the Bill & Melinda Gates Foundation Grand Challenges Explorations grant number OPP1024642 ‘Fusogenic nanoparticles for combined anti-HIV/contraception.’

Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

U.S. baby’s HIV infection cured through very early treatment

Sun, 3 Mar 2013 21:29 GMT

Reuters

* Mississippi girl’s case is the first account of an HIV cure in an infant

* Doctors started treatment within 30 hours of the child’s birth

By Julie Steenhuysen

CHICAGO, March 3 (Reuters) – A baby girl in Mississippi who was born with HIV has been cured after very early treatment with standard drug therapy, U.S. researchers reported on Sunday, in a potentially ground-breaking case that could offer insights on how to eradicate HIV infection in its youngest victims.

The child’s story is the first account of an infant achieving a so-called functional cure, a rare event in which a person achieves remission without the need for drugs and standard blood tests show no signs that the virus is making copies of itself.

More testing needs to be done to see if the treatment would have the same effect on other children, but the results could change the way high-risk babies are treated and possibly lead to a cure for children with HIV, the virus that causes AIDS.

“This is a proof of concept that HIV can be potentially curable in infants,” said Dr. Deborah Persaud, a virologist at Johns Hopkins University in Baltimore, who presented the findings at the Conference on Retroviruses and Opportunistic Infections in Atlanta.

The child’s story is different from the now famous case of Timothy Ray Brown, the so-called “Berlin patient,” whose HIV infection was completely eradicated through an elaborate treatment for leukemia in 2007 that involved the destruction of his immune system and a stem cell transplant from a donor with a rare genetic mutation that resists HIV infection.

Instead of Brown’s costly treatment, the Mississippi baby’s case involved the use of a cocktail of widely available drugs already used to treat HIV infection in infants.

When the baby girl was born in a rural hospital, her mother had just tested positive for HIV infection. Because her mother had not received any prenatal HIV treatment, doctors knew the child was born at high risk of being infected. So they transferred the baby to the University of Mississippi Medical Center in Jackson, where she came under the care of Dr. Hannah Gay, a pediatric HIV specialist.

Because of her high infection risk, Dr. Gay put the infant on a cocktail of three standard HIV-fighting drugs when she was just 30 hours old, even before lab tests came back confirming her infection. In more typical pregnancies when an HIV-infected mother has been given drugs to reduce the risk of transmission to her child, the baby would only have been given a single drug to reduce her infection risk.

Researchers believe this early use of antiviral treatment likely resulted in the infant’s cure by keeping the virus from forming hard-to-treat pools of cells known as viral reservoirs, which lie dormant and out of the reach of standard medications. These reservoirs rekindle HIV infection in patients who stop therapy, and they are the reason most HIV-infected individuals need lifelong treatment to keep the infection at bay.

10-MONTH GAP

After starting on treatment, the baby’s immune system responded and tests showed levels of the virus were diminishing until it was undetectable 29 days after birth. The baby received regular treatment for 18 months, but then stopped coming to appointments for a period of about 10 months, when her mother said she was not given any treatment. The doctors did not say why the mother stopped coming.

When the child came back under the care of Dr. Gay, she ordered standard blood tests to see how the child was faring before resuming antiviral therapy.

What she found was surprising. The first blood test did not turn up any detectible levels of HIV. Neither did the second. And tests for HIV-specific antibodies – the standard clinical indicator of HIV infection – also remained negative.

“At that point, I knew I was dealing with a very unusual case,” Dr. Gay said.

Baffled, Dr. Gay turned to her friend and longtime colleague, Dr. Katherine Luzuriaga of the University of Massachusetts, and she and Persaud did a series of sophisticated lab tests on the child’s blood.

The first looked for silent reservoirs of the virus where it remains dormant but can replicate if activated. That is detected in a type of immune cell known as a CD4 T-cell. After culturing the child’s cells, they found no sign of the virus.

Then, the team looked for HIV DNA, which indicates that the virus has integrated itself into the genetic material of the infected person. This test turned up such low levels that it was just above the limit of the test’s ability to detect it.

The third test looked for bits of genetic material known as viral RNA. They only found a single copy of viral RNA in one of the two tests they ran.

Because there is no detectible virus in the child’s blood, the team has advised that she not be given antiretroviral therapy (ART), whose goal is to block the virus from replicating in the blood. Instead, she will be monitored closely.

Dr. Rowena Johnston, vice president and director of research for the Foundation for AIDS Research, which helped fund the study, said the fact that the cure was achieved by antiretroviral therapy alone makes it “imperative that we learn more about a newborn’s immune system, how it differs from an adult’s and what factors made it possible for the child to be cured.”

Because the child’s treatment was stopped, the doctors were able to identify that this child had been cured, raising questions about whether other children who received early treatment and have undetectable viral loads may also be cured without knowing it.

But the doctors warned parents not to be tempted to take their children off treatment to see if the virus comes back. Normally, when patients stop taking their medications, the virus comes roaring back, and treatment interruptions increase the risk that the virus will develop drug resistance.

“We don’t want that,” Dr. Gay said. “Patients who are on successful therapy need to stay on their successful therapy until we figure out a whole lot more about what was going on with this child and what we can do for others in the future.”

The researchers are trying to find biomarkers that would offer a rationale to consider stopping therapy within the context of a clinical trial. If they can learn what caused the child to clear her virus, they hope to replicate that in other babies, and eventually learn to routinely prevent infections.  (Reporting by Julie Steenhuysen; Editing by Jilian Mincer and Sandra Maler)

http://www.trust.org/alertnet/news/us-babys-hiv-infection-cured-through-very-early-treatment/

Newly identified natural protein blocks HIV, other deadly viruses

EEV:  25-hydroxycholesterol/Statin?

Contact: Enrique Rivero erivero@mednet.ucla.edu 310-794-2273 University of California – Los Angeles Health Sciences

A team of UCLA-led researchers has identified a protein with broad virus-fighting properties that potentially could be used as a weapon against deadly human pathogenic viruses such as HIV, Ebola, Rift Valley Fever, Nipah and others designated “priority pathogens” for national biosecurity purposes by the National Institute of Allergy and Infectious Disease.

In a study published in the January issue of the journal Immunity, the researchers describe the novel antiviral property of the protein, cholesterol-25-hydroxylase (CH25H), an enzyme that converts cholesterol to an oxysterol called 25-hydroxycholesterol (25HC), which can permeate a cell’s wall and block a virus from getting in.

Interestingly, the CH25H enzyme is activated by interferon, an essential antiviral cell-signaling protein produced in the body, said lead author Su-Yang Liu, a student in the department of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA.

“Antiviral genes have been hard to apply for therapeutic purposes because it is difficult to express genes in cells,” said Liu, who performed the study with principal investigator Genhong Cheng, a professor of microbiology, immunology and molecular genetics. “CH25H, however, produces a natural, soluble oxysterol that can be synthesized and administered.

“Also, our initial studies showing that 25HC can inhibit HIV growth in vivo should prompt further study into membrane-modifying cholesterols that inhibit viruses,” he added.

The discovery is particularly relevant to efforts to develop broad-spectrum antivirals against an increasing number of merging viral pathogens, Liu said.

Working with Jerome Zack, a professor of microbiology, immunology and molecular genetics and an associate director of the UCLA AIDS Institute, the researchers initially found that 25HC dramatically inhibited HIV in cell cultures. Next, they administered 25HC in mice  implanted with human tissues and found that it significantly reduced their HIV load within seven days. The 25HC also reversed the T-cell depletion caused by HIV.

By contrast, mice that had the CH25H gene knocked out were more susceptible to a mouse gammaherpes virus, the researchers found.

In collaboration with Dr. Benhur Lee, a professor of pathology and laboratory medicine and a member of the UCLA AIDS Institute, they discovered that 25HC inhibited HIV entry into the cell. Furthermore, in cell cultures, it was found to inhibit the growth of other deadly viruses, such as Ebola, Nipah and the Rift Valley Fever virus.

Intriguingly, CH25H expression in cells requires interferon. While interferon has been known for more than 60 years to be a critical part of the body’s natural defense mechanism against viruses, the protein itself does not have any antiviral properties. Rather, it triggers the expression of many antiviral genes. While other studies have identified some antiviral genes that are activated by interferon, this research gives the first description of an interferon-induced antiviral oxysterol through the activation of the enzyme CH25H. It provides a link to how interferon can cause inhibition of viral membrane fusion, Liu said.

He noted some weaknesses in the research. For instance, 25HC is difficult to deliver in large doses, and its antiviral effect against Ebola, Nipah and other highly pathogenic viruses have yet to be tested in vivo. Also, the researchers still need to compare 25HC’s antiviral effect against other HIV antivirals.

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Additional study co-authors were Roghiyh Aliyari, Kelechi Chikere, Matthew D. Marsden and Olivier Pernet, of UCLA; Jennifer K. Smith, Rebecca Nusbaum and Alexander N. Frieberg, of the University of Texas–Galveston; and Guangming Li, Haitao Guo and Lishan Su, of the University of North Carolina–Chapel Hill.

The National Institutes of Health (grants R01 AI078389, AI069120, AI080432, AI095097, AI077454, AI070010 and AI028697), the Warsaw Fellowship, the UCLA Center for AIDS Research (CFAR), the UCLA AIDS Institute, the UCLA Clinical and Translational Science Institute (CTSI), and the Pacific Southwest Regional Center of Excellence (PSWRCE) for Biodefense and Emerging Infectious Diseases funded this study.

The UCLA AIDS Institute, established in 1992, is a multidisciplinary think tank drawing on the skills of top-flight researchers in the worldwide fight against HIV and AIDS, the first cases of which were reported in 1981 by UCLA physicians. Institute members include researchers in virology and immunology, genetics, cancer, neurology, ophthalmology, epidemiology, social sciences, public health, nursing and disease prevention. Their findings have led to advances in treating HIV, as well as other diseases, such as hepatitis B and C, influenza and cancer.

For more news, visit the UCLA Newsroom and follow us on Twitter.

A ‘neurosteroid’ found to prevent brain injury caused by HIV/AIDS : DHEA-S

Contact: Cody Mooneyhan cmooneyhan@faseb.org 301-634-7104 Federation of American Societies for Experimental Biology

New research in The FASEB Journal suggests that a network of steroid molecules found in the brain is disrupted during HIV infection, and treatment with the steroid DHEA-S prevents brain damage

Bethesda, MD—A team of scientists from Canada, Thailand and Morocco have found that DHEA-S may prevent neurocognitive impairment that affects a significant percentage of AIDS patients. In a report appearing in the February 2013 issue of The FASEB Journal, they describe how a network of steroid molecules found in the brain, termed “neurosteroids,” is disrupted during HIV infection leading to brain damage. This suggests that treatment with one of these steroid molecules, called DHEA-S, may offset the disruption caused by the virus to prevent or reduce brain damage.

“From these studies, we have gained a better understanding of how HIV injures the brain during AIDS, together with developing a new treatment approach for the resulting neurological disabilities arising from HIV/AIDS,” said Christopher Power, M.D., co-author of this study from the Department of Medicine at the Medical Research Centre at the University of Alberta in Edmonton, Canada.

To make their discovery, Power and colleagues initially found that neurosteroid enzyme levels were suppressed in the brains of people with HIV/AIDS and that a neurosteroid molecule, DHEA-S, prevented damage to cultured brain cells (neurons) caused by HIV. Then, using an animal model of AIDS, they showed that treatment with DHEA-S prevented neuronal damage in the brain by reducing the adverse effects of HIV. Neurosteroids have already been proposed as treatments for epilepsy, head injury, post-traumatic stress disorder and depression, and these findings extend the potential treatment applications for neurosteroid-related molecules.

“Most people know that AIDS wreaks total havoc on our immune systems,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, “but far fewer people know that the disease can also lead to noticeable brain damage. This research study offers an explanation why this occurs as well as a possible solution for preventing it. The next steps, of course, involve looking into whether or not people will benefit from some form of DHEA-S treatment.”

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Receive monthly highlights from The FASEB Journal by e-mail. Sign up at http://www.faseb.org/fjupdate.aspx.

The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB). It is among the most cited biology journals worldwide according to the Institute for Scientific Information and has been recognized by the Special Libraries Association as one of the top 100 most influential biomedical journals of the past century. FASEB is composed of 26 societies with more than 100,000 members, making it the largest coalition of biomedical research associations in the United States. Its mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to its member societies and through collaborative advocacy.

Details: Ferdinand G. Maingat, Maria J. Polyak, Amber M. Paul, Pornpun Vivithanaporn, Farshid Noorbakhsh, Samir Ahboucha, Glen B. Baker, Keir Pearson, and Christopher Power. Neurosteroid-mediated regulation of brain innate immunity in HIV/AIDS: DHEA-S suppresses neurovirulence.  FASEB J February 2013 27:725-737; doi:10.1096/fj.12-215079;  http://www.fasebj.org/content/27/2/725.abstract.

Cream with green tea extract hinders HIV transmission: study

2009 study posted for filing

(AFP)–May 19, 2009

WASHINGTON (AFP) – A chemical found in green tea helps inhibit sexual transmission of the virus which causes AIDS, said a study Tuesday that recommends using the compound in vaginal creams to supplement antiretrovirals.

Medical experts at Germany’s University of Heidelberg said the compound could be a low-cost arrow in the quiver of medical weapons to fight the spread of HIV in research-poor countries.

The researchers said they determined that the green tea polyphenol, or vegetable tannin, called epigallocatechin-3-gallate (EGCG) is capable of neutralizing a protein in sperm which serves as a vector for viral transmission during sex.

EGCG degrades what is known as a semen-derived enhancer of virus infection, or SEVI, described in the study as “an important infectivity factor of HIV.”

Writing in the online edition of the Proceedings of the National Academy of Sciences, the researchers said they “recently identified a peptide fraction in human semen that consistently enhanced HIV-1 infection.”

SEVIs capture viral elements and attach them to the surface of target cells, enhancing cell fusion and decreasing a cell’s ability to repel viral threats.

EGCG “targets SEVI for degradation” and “abrogates semen-mediated enhancement of HIV-1 infection in the absence of cellular toxicity,” said the researchers, some of whom work at the university’s Heinrich-Pette-Institute for Experimental Virology and Immunology.

Because of its effects on semen-based HIV transmission threats, the study’s authors said “EGCG appears to be a promising supplement to antiretroviral microbicides to reduce sexual transmission of HIV-1.”

With the vast majority of the world’s 33 million people with HIV infected through heterosexual sex, and as 96 percent of new infections occur in poor and developing nations, researchers said the use of green tea EGCG in topical creams would “provide a simple and affordable prevention method” to guard against HIV transmission.

Green tea, which originated in China and is widely consumed in Asia, the Middle East and growing numbers of western countries, is already popular for its antioxidant qualities.

Diverse intestinal viruses may play a role in AIDS progression

Contact: Elisabeth Lyons
elyons@cell.com
617-386-2121
Cell Press

In monkeys and humans with AIDS, damage to the gastrointestinal tract is common, contributing to activation of the immune system, progressive immune deficiency, and ultimately advanced AIDS. How this gastric damage occurs has remained a mystery, but now researchers reporting in the Cell Press journal Cell provide new clues, implicating the presence of potentially pathogenic virus species other than the main virus that causes AIDS. The findings could provide an opportunity to explain and eventually intervene in the processes that lead to AIDS progression.

To investigate what causes gastrointestinal damage in monkeys and humans with AIDS, researchers used a sequencing method that allows them to obtain genetic sequences of all of the bacterial, viral, and other organisms residing in the gastrointestinal tract. Using this technique, they examined the feces of monkeys with SIV-induced AIDS, monkeys without SIV infection, and monkeys infected with SIV strains that do not cause AIDS. (SIV is the monkey counterpart to HIV.)

“We found that the gastrointestinal tract of the animals with AIDS contained a large number of previously undescribed viruses—including potential pathogens, but we did not see any obvious changes in the bacteria. This means that previously unrecognized viruses may contribute to AIDS disease progression in monkeys,” explains co-author Dr. Dan Barouch, of Harvard Medical School and the Beth Israel Deaconess Medical Center, in Boston. It’s not clear why monkeys with AIDS have more intestinal viruses, but it may be related to their compromised immune system.

The researchers also noted that some of the viruses in the feces of monkeys with AIDS were also found circulating in the animals’ blood. In addition, many were RNA viruses, meaning that their genetic material is made up of RNA rather than DNA. “This is the first time anyone has looked at both DNA- and RNA-based organisms in the fecal matter in association with AIDS. The striking finding of so many RNA viruses to go along with DNA viruses opens up the broader issue of whether we need to rethink how we study the genomes of microorganisms that may affect disease,” says senior author Dr. Herbert Virgin, of the Washington University School of Medicine, in Saint Louis.

In addition to providing new information on how AIDS advances, and therefore how to potentially intervene to slow it down, the results indicate that the viruses found in AIDS patients’ intestines could indicate how progressive their disease will be.

 

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Handley et al.: “Pathogenic simian immunodeficiency virus infection is associated with expansion of the enteric virome.”

Selenium may slow march of AIDS

2008 study posted for filing

Contact: Amitabh Avasthi
axa47@psu.edu
814-865-9481
Penn State

Increasing the production of naturally occurring proteins that contain selenium in human blood cells slows down multiplication of the AIDS virus, according to biochemists.

“We have found that increasing the expression of proteins that contain selenium negatively affects the replication of HIV,” said K. Sandeep Prabhu, Penn State assistant professor of immunology and molecular toxicology. “Our results suggest a reduction in viral replication by at least 10-fold.”

Selenium is a micronutrient that the body needs to maintain normal metabolism. Unlike other nutrients, which bind to certain proteins and modulate the protein’s activity, selenium gets incorporated into proteins in the form of an amino acid called selenocysteine.

These proteins – selenoproteins – are especially important in reducing the stress caused by an infection, thereby slowing its spread.

Upon infecting a person, the virus quickly degrades selenoproteins so that it can replicate efficiently. It is unclear just how the virus is able to silence these proteins but Prabhu and his colleagues believe that stress inflicted on cells by the rapidly dividing virus, which produces a key protein known as Tat, is the likely culprit.

Tat is one of about 14 odd proteins produced by HIV during the first stage of infection. The job of these proteins is to trigger the expression of all the other genes that the virus needs to sustain itself. In addition, Tat also plays a key role in helping the virus replicate.

One of the proteins that targets Tat is a selenoprotein known as TR1.

“Since HIV targets the selenoproteins, we thought that the logical way to deal with the virus is to increase the expression of such proteins in the body,” explained Prabhu, whose team’s findings are outlined this week (Nov. 28) in the Journal of Biological Chemistry.

Researchers first isolated blood cells from healthy human volunteers who did not have HIV, and infected those cells with the virus. Next, they added tiny amounts of a selenium compound – sodium selenite – into the cell culture to see the effect on viral replication.

Results from the tests indicate that the addition of selenium inhibits the replication of HIV at least 10-fold, compared to cell cultures in which no selenium is added. When the researchers selectively reduced production of the selenium containing TR1 protein, they observed a 3.5-fold increase in viral replication.

“This confirms that while increasing the expression of TR1 has a negative impact on the replication of HIV, reducing it helps the virus replicate more efficiently,” explained Prabhu. He believes that TR1 works by upsetting the chemical structure of Tat, which in turn reduces the virus’ ability to replicate.

“Once we fully understand the function of these selenium proteins, it will give us a handle to come up with more effective drugs,” said Prabhu, whose work is partly funded by the National Institutes of Health.

 

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Other researchers on the paper include Parisa Kalantari, post-doctoral scholar; Vivek Narayan, graduate student; Kambadur Muralidhar, visiting faculty; Ujjawal H. Gandhi, graduate student; and Hema Vunta, graduate student, all at Penn State; Satish K. Natarajan, research associate, University of Nebraska; and Andrew J. Henderson, associate professor of medicine and microbiology, Boston University.

 

Popular HIV drug commonly prescribed anti-retroviral drug efavirenz attacks brain cells

Contact: Stephanie Desmon sdesmon1@jhmi.edu 410-955-8665 Johns Hopkins Medicine

Popular HIV drug may cause memory declines

Johns Hopkins study suggests the commonly prescribed anti-retroviral drug efavirenz attacks brain cells

The way the body metabolizes a commonly prescribed anti-retroviral drug that is used long term by patients infected with HIV may contribute to cognitive impairment by damaging nerve cells, a new Johns Hopkins research suggests.

Nearly 50 percent of people infected with HIV will eventually develop some form of brain damage that, while mild, can affect the ability to drive, work or participate in many daily activities. It has long been assumed that the disease was causing the damage, but Hopkins researchers say the drug efavirenz may play a key role.

People infected with HIV typically take a cocktail of medications to suppress the virus, and many will take the drugs for decades. Efavirenz is known to be very good at controlling the virus and is one of the few that crosses the blood-brain barrier and can target potential reservoirs of virus in the brain. Doctors have long believed that it might be possible to alleviate cognitive impairment associated with HIV by getting more drugs into the brain, but researchers say more caution is needed because there may be long-term effects of these drugs on the brain.

“People with HIV infections can’t stop taking anti-retroviral drugs. We know what happens then and it’s not good,” says Norman J. Haughey, Ph.D., an associate professor of neurology at the Johns Hopkins University School of Medicine. “But we need to be very careful about the types of anti-retrovirals we prescribe, and take a closer look at their long-term effects. Drug toxicities could be a major contributing factor to cognitive impairment in patients with HIV.”

For the study led by Haughey and described online in the Journal of Pharmacology and Experimental Therapeutics, researchers obtained samples of blood and cerebrospinal fluid from HIV-infected subjects enrolled in the NorthEastern AIDS Dementia study who were taking efavirenz. Researchers looked for levels of the drug and its various metabolites, which are substances created when efavirenz is broken down by the liver. Performing experiments on neurons cultured in the lab, the investigators examined the effects of 8-hydroxyefavirenz and other metabolites  and found major structural changes when using low levels of 8-hydroxyefavirenz, including the loss of the important spines of the cells.

Haughey and his colleagues found that 8-hydroxyefavirenz is 10 times more toxic to brain cells than the drug itself and, even in low concentrations, causes damage to the dendritic spines of neurons. The dendritic spine is the information processing point of a neuron, where synapses — the structures that allow communication among brain cells — are located.

In the case of efavirenz, a minor modification in the drug’s structure may be able block its toxic effects but not alter its ability to suppress the virus. Namandje N. Bumpus, Ph.D., one of the study’s other authors, has found a way to modify the drug to prevent it from metabolizing into 8-hydroxyefavirenz while maintaining its effectiveness as a tool to suppress the HIV virus.

“Finding and stating a problem is one thing, but it’s another to be able to say we have found this problem and here is an easy fix,” Haughey says.

Haughey says studies like his serve as a reminder that while people infected with HIV are living longer than they were 20 years ago, there are significant problems associated with the drugs used to treat the infection.

“Some people do seem to have this attitude that HIV is no longer a death sentence,” he says. “But even with anti-retroviral treatments, people infected with HIV have shortened lifespans and the chance of cognitive decline is high. It’s nothing you should treat lightly.”

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The study was supported by grants from the National Institute on Alcohol Abuse and Alcoholism (AA0017408), the National Institute of Mental Health (MH077543, MH075673 and MH71150), the National Institute on Aging (AG034849) and the National Institute of Neurological Disorders and Stroke (NS049465).

Other Hopkins researchers involved in the study include Luis B. Tovar y Romo, Ph.D.; Lindsay B. Avery, Ph.D.; Ned Sacktor, M.D.; and Justin McArthur, M.B.B.S., M.P.H.

For more information:http://www.hopkinsmedicine.org/neurology_neurosurgery/research/jhu_nimh/researchers

Study shows common vitamin and other micronutrient supplements reduce risks of TB recurrence

Re-Post Filing 2008

Contact: Steve Baragona
sbaragona@idsociety.org
703-299-0412
Infectious Diseases Society of America

New findings show a link between micronutrient supplementation and reduced risk of recurrence during tuberculosis chemotherapy, according to a study published in the June 1 issue of The Journal of Infectious Diseases, now available online.

Nutritional assessment and support in tuberculosis therapy, once common before the advent of anti-TB drugs, is no longer an integral part of clinical therapy in most low-income countries even though poor nutrition impairs the immune system and leads to risk of further infection and relapse.

In Tanzania, Eduardo Villamor, MD, DrPH, of the Harvard School of Public Health, and a team of researchers conducted a randomized trial of micronutrients using doses of vitamins A, B-complex, C, E, and selenium or placebo in 887 patients receiving tuberculosis therapy, who were then followed for a medium of 43 months; 471 were HIV-coinfected and not receiving antiretroviral therapy and 416 were HIV-uninfected.

The study showed that micronutrient supplementation was associated with reduced rates of TB recurrence. In the study, both HIV-infected and uninfected patients with pulmonary TB who were receiving the supplements had a decreased risk of TB recurrence during the next few months after the TB culture had become negative: 45 percent overall and 63 percent in HIV-infected patients. Supplementation also reduced the incidence of peripheral neuropathy by 57 percent, irrespective of HIV status, and increased the levels of certain cells (CD3 and CD4) important in immune response in HIV-uninfected patients.

As Villamor noted, “We found that providing micronutrients to patients with tuberculosis who were undergoing anti-TB treatment appeared to decrease the risk of recurrences. This effect was stronger in patients infected with HIV than in those who were HIV-negative. This could be relevant because TB reactivation is common among HIV-infected persons.” Villamor further noted, “that it will be important to find out whether micronutrients improve the outcome of TB treatment in TB-HIV co-infected patients who are undergoing antiretroviral therapy.”

Christine Stabell Benn, MD, and colleagues in Copenhagen noted in their accompanying editorial that results to date relating to TB recurrence and mortality are inconsistent, with previous studies using different dosages and combinations of micronutrients. Dr. Stabell pointed out that the promising results of the Villamor study show that further investigations are needed to develop optimal combinations of micronutrients that can be provided inexpensively in TB therapy to reduce relapses and increase survival.

 

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Fast Facts:

1) Supplements of common vitamins and other micronutrients may reduce the risk of recurrence in patients receiving tuberculosis treatment.

2) Further studies of micronutrient supplementation offer the potential for an inexpensive treatment strategy for vitamin-deficient tuberculosis patients in low-income countries.

3) The effects of micronutrient supplementation in TB-HIV co-infected patients undergoing antiretroviral therapy have yet to be studied.

Founded in 1904, The Journal of Infectious Diseases is the premier publication in the Western Hemisphere for original research on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune mechanisms. Articles in JID include research results from microbiology, immunology, epidemiology, and related disciplines. JID is published under the auspices of the Infectious Diseases Society of America (IDSA). Based in Arlington, Va., IDSA is a professional society representing more than 8,000 physicians and scientists who specialize in infectious diseases. Nested within the IDSA, the HIV Medicine Association (HIVMA) is the professional home for more than 3,600 physicians, scientists and other health care professionals dedicated to the field of HIV/AIDS. HIVMA promotes quality in HIV care and advocates policies that ensure a comprehensive and humane response to the AIDS pandemic informed by science and social justice. For more information, visit www.idsociety.org and www.hivma.org.

Pitt cancer researchers find key oncoprotein in Merkel cell carcinoma – Cancer Virus

Contact: Anita Srikameswaran SrikamAV@upmc.edu 412-578-9193 University of Pittsburgh Schools of the Health Sciences

PITTSBURGH, Aug. 15 – Researchers at the University of Pittsburgh Cancer Institute (UPCI) have identified the oncoprotein that allows a common and usually harmless virus to transform healthy cells into a rare but deadly skin cancer called Merkel Cell Carcinoma (MCC). Their findings, published today in the Journal of Clinical Investigation, could improve diagnosis for MCC and may help in understanding how other cancers arise.

Three years ago, Yuan Chang, M.D., and Patrick S. Moore, M.D., M.P.H., in the Cancer Virology Program at UPCI, discovered a new human cancer virus, called Merkel Cell polyomavirus (MCV), that causes most cases of MCC. But until now, it was not clear how the virus triggered cancer development.

To figure that out, lead author Masahiro Shuda, Ph.D., UPCI research associate, and the team systematically examined the viral proteins that might trigger cancer cell growth. After establishing human MCC cell lines, the scientists learned that knocking out a viral protein called “small tumor protein,” or sT, stopped the cancer cells from replicating. When they introduced sT into healthy cells in the lab, the cells took on the characteristics of cancer cells.

“This was a surprise because the viral sT proteins from other similar viruses that cause cancers in laboratory animals do not directly increase cancer activity in cells,” Dr. Shuda said. “Once we found this, we had to next understand the biological mechanisms that make MCV sT a cancer-causing protein, or oncoprotein.”

The MCV sT triggers a cellular process called “cap-dependent translation” that allows certain cellular oncoproteins to be made, Dr. Moore explained. Although the cancers caused by MCV are rare, the virus is important because it helps scientists pinpoint cell pathways that are key to more common cancers. These cancers also might activate cap-dependent translation through a DNA mutation rather than through a virus infection.

In related studies recently published by the team in Emerging Infectious Diseases, MCV was shown to normally infect four out of five healthy adults, where it remains a silent resident in skin cells without causing any symptoms. Only when specific mutations occur in the DNA of the virus―for example, by ultraviolet light exposure―does it have potential to cause cancer. The researchers are now working to identify new agents to target MCC cancer cells that may be more active and less toxic.

MCV is the first virus in the family of polyomaviruses shown to cause human cancer, but six other polyomaviruses have recently been discovered as inapparent infections of people, and scientists are actively seeking to find out if they are additional, cancer-causing viruses as well. MCV is the second human cancer virus found by the Chang-Moore laboratory, which previously also discovered the virus causing Kaposi’s sarcoma – the most common cancer among AIDS patients.

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Other co-authors are Hyun Jin Kwun, Ph.D., and Huichen Fung, Ph.D., both of the Cancer Virology Program. The research was funded by the National Institutes of Health, the American Cancer Society and UPCI. Dr. Chang is an American Cancer Society Professor of pathology, and Dr.  Moore is an American Cancer Society Professor of microbiology and molecular genetics, Pitt School of Medicine

Newly discovered virus linked to deadly skin cancer : Merkel cell polyomavirus

Contact: Michele Baum BaumMD@upmc.edu 412-647-3555 University of Pittsburgh Schools of the Health Sciences

Novel sequencing technique used at the University of Pittsburgh Cancer Institute reveals new cancer virus; reported in the journal Science

PITTSBURGH, Jan. 17 – A new strategy to hunt for human viruses described in this week’s issue of the journal Science by the husband-and-wife team who found the cause of Kaposi’s sarcoma has revealed a previously unknown virus strongly associated with another rare but deadly skin cancer called Merkel cell carcinoma. In the paper, University of Pittsburgh Cancer Institute (UPCI) researchers, Huichen Feng, Ph.D., Masahiro Shuda, Ph.D., Yuan Chang, M.D., and Patrick Moore, M.D., M.P.H., explain a nearly decade-long effort to harness the sequencing technology to identify the virus, which they call Merkel cell polyomavirus (MCV). While the research team emphasizes that their work does not prove MCV to be the cause of Merkel cell carcinoma, if the findings are confirmed, they may lead to new cancer treatment and prevention options.

“This is the first polyomavirus to be strongly associated with a particular type of human tumor,” said Dr. Moore, professor of microbiology and molecular genetics at the University of Pittsburgh School of Medicine and leader of the molecular virology program at UPCI. “Although polyomaviruses have been studied in relation to cancer development for years, the weight of scientific evidence had been leaning toward the view that these viruses do not cause human cancers.”

Polyomaviruses are a group of viruses that have been shown to cause cancers in animals for more than 50 years. But Dr. Moore noted that additional research is needed to determine what role, if any, MCV plays in human cancer development.

A rare but extremely aggressive cancer that spreads rapidly into other tissues and organs, Merkel cell carcinoma (MCC) develops from specialized nerve cells that respond to touch or pressure. The incidence of MCC has tripled over the past 20 years to about 1,500 cases a year, especially among people whose immune systems are compromised by AIDS or transplant-related immunosuppressant drugs. About half of patients with advanced MCC live nine months or less, and some two-thirds of MCC patients die within five years.

“If these findings are confirmed, we can look at how this new virus contributes to a very bad cancer with high mortality, and, just as importantly, use it as a model to understand how cancers occur and the cell pathways that are targeted,” added Dr. Moore. “Information that we gain could possibly lead to a blood test or vaccine that improves disease management and aids in prevention.”

For example, vaccines are now available against human papillomavirus (HPV) to prevent cervical cancer, noted Dr. Chang, professor of pathology. “MCV is another model that may increase our understanding of how cancers arise, with possibly important implications for non-viral cancers like prostate or breast cancer.”

MCV has additional similarities to HPV since both viruses integrate into the tumor cell genome but not the genome of healthy cells. This integration destroys the virus’s ability to replicate normally and may be the first critical step in MCC development.

The Pittsburgh team analyzed nearly 400,000 messenger RNA genetic sequences from four samples of MCC tumor tissue using a technique refined in their lab called digital transcriptome subtraction (DTS). Comparing the sequences expressed by the tumor genome to gene sequences mapped by the Human Genome Project, the researchers systematically subtracted known human sequences, leaving a group of genetic transcripts that might be from a foreign organism.

One sequence was similar to but distinct from all known viruses. The team went on to show that this sequence belonged to a new polyomavirus present in eight of 10 (80 percent) Merkel cell tumors they tested but only five of 59 (8 percent) control tissues from various body sites and four of 25 (16 percent) control skin tissues.

Although MCV is most commonly found in Merkel cell tumors, it also can be found in healthy people. The most important distinguishing feature is that MCV integrates into tumor cells in what is known as a monoclonal pattern, indicating that it infects the cell before the cell becomes cancerous. Tests on six of the eight MCV-positive tumors confirmed that viral DNA was integrated within the tumor genome in this monoclonal pattern, suggesting that infection with MCV could be a trigger for tumor formation. The Pittsburgh team subsequently has confirmed these results with additional tumor specimens.

Clues from elsewhere in the biomedical literature point to the existence of MCV, which has a genetic structure that is closely related to an African green monkey virus found in Germany in the 1970s. Researchers have found antibody evidence from blood tests that indicates some 15 percent to 25 percent of adults are infected with the still undiscovered human relative of this monkey virus. If MCV turns out to be this long-sought infection, then more than 1 billion people worldwide could already be infected.

“But again, look to the example of HPV,” said Dr. Moore. “Although up to 50 percent of sexually active young women are infected with HPV, a small proportion may actually get cervical cancer.”

Even if MCV is proven to play a role in MCC, Dr. Chang also cautioned that the virus is likely to be just a part of a much larger picture.

“Now we need to find out how it works,” she said. “Once the virus integrates, it could express an oncoprotein, or it could knock out a gene that suppresses tumor growth. Either way, the results are bound to be interesting.”

This is the second tumor-associated virus discovered by Drs. Moore and Chang, a husband-and-wife research team who also discovered Kaposi’s sarcoma-associated herpesvirus (KSHV) in 1993. KSHV, which causes Kaposi’s sarcoma, is the most common malignancy in AIDS patients and the most common cancer in Africa. To find KSHV, Drs. Moore and Chang used a different method to physically subtract human genetic sequences from Kaposi’s sarcoma tumors, leaving fragments of viral DNA.

Viruses, and some bacteria and parasites, are estimated to cause at least 20 percent of cancers worldwide. Over the past 40 years, few cancer-causing viruses have been confirmed in humans, including KSHV. Most of these viruses express cancer-causing proteins, called oncoproteins, in infected cells. Polyomaviruses, including MCV, possess an oncoprotein that has been shown to cause cancer after infection in animals. If MCV is confirmed to play a role in human cancer, it will be the eighth human tumor virus discovered.

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Funding for the study was provided by the National Institutes of Health and the Pennsylvania Department of Health

Reposted For Filing

21st Health Research Report 26 DEC 2007 – Reconstruction

21st Health Research Report 26 DEC 2007 – Reconstruction (link below)

In This issue:

1. Elective Caesareans carry increased risk of breathing problems
2. Cholesterol-lowering drugs and the risk of hemorrhagic stroke
3. Turkish health workers condone wife beating
4. New clinical data shows chromium picolinate improves cognitive function
5. Green tea may protect brain cells against Parkinson’s disease
6. Vitamin B12 function may be diminished by excessive folate
7. Does treating worms in people with HIV slow progression to AIDS?
8. Walking and moderate exercise help prevent dementia
9. Breath test can discriminate between a bacterial overgrowth and IBS
10. Why don’t we get cancer all the time?
11. Why exertion leads to exhaustion
12. Why fish oil is good for you
 
http://healthresearchreport.me/2007/12/26/21st-health-research-report-26-dec-2007-reconstruction/

Does treating worms in people with HIV slow progression to AIDS?

Of the 25 million people infected with HIV-1 in Africa, as many as half are thought to be co-infected with worms (helminths), and there is evidence that these worms may result in a more rapid progression of HIV infection to AIDS. Does treating these worms (“de-worming”) slow down this progression.

In a new study published in the open access journal PLoS Neglected Tropical Diseases, Judd Walson and Grace John-Stewart at the University of Washington, Seattle, USA set out to answer this question. Their study found that there were simply not enough data to make any firm conclusions, and they call for larger, well-designed studies to help come to a definitive answer.

There were five studies in the final analysis. All five were limited by short follow up times. Only one of these was a randomized controlled trial (RCT)—it compared the effects of treating worms in people with HIV against no treatment. The trial did find some benefit from the de-worming treatment. In patients with HIV who did not receive the de-worming treatment, their viral load (a measure of the amount of HIV in their bloodstream) went up. In contrast, the viral load of patients who were de-wormed remained stable. However, de-worming was not associated with improvements in the patients’ immune status (as measured by the CD4 count) or in their clinical condition.

*Reposted at Request

New salmonella-based ‘clean vaccines’ aid the fight against infectious disease:To accomplish this, a recombinant strain of Salmonella was constructed using genes from another pathogen, Francisella tularensis

* They are using genes from tularensis ” inhaling as few as 10 bacteria could be potentially deadly ” I feel uncomfortable with the Gates foundation funding support utilizing a Bioweapon strain of  Rabbit Fever?

 

New salmonella-based ‘clean vaccines’ aid the fight against infectious disease

A powerful new class of therapeutics, known as recombinant attenuated Salmonella vaccines (RASV), holds great potential in the fight against fatal diseases including hepatitis B, tuberculosis, cholera, typhoid fever, AIDS and pneumonia.

Now, Qingke Kong and his colleagues at the Biodesign Institute at Arizona State University, have developed a technique to make such vaccines safer and more effective. The group, under the direction of Dr. Roy Curtiss, chief scientist at Biodesign’s Center for Infectious Diseases and Vaccinology, demonstrated that a modified strain of Salmonella showed a five-fold reduction in virulence in mice, while preserving strong immunogenic properties.

Their findings appear in the cover story of the current issue of the Journal of Immunology.

Streptococcus pneumoniae, an aerobic bacterium, is the causative agent of diseases including community-acquired pneumonia, otitis media, meningitis, and bacteremia. It remains a leading killer—childhood pneumonia alone causing some 3 million fatalities annually, mostly in poorer countries.

Existing vaccines are inadequate for protecting vulnerable populations for several reasons. Heat stabilization and needle injection are required, which are often impractical for mass inoculation efforts in the developing world. Repeated doses are also needed to induce full immunity. Finally, the prohibitively high costs of existing vaccines often deprive those who need them most.  The problem is exacerbated by the recent emergence of antibiotic-resistant strains of pneumococcus causing the disease, highlighting the urgency of developing safe, effective, and lower-cost antipneumococcal vaccines.

One of the most promising strategies for new vaccine development is to use a given pathogen as a cargo ship to deliver key antigens from the pathogen researchers wish to vaccinate against. Salmonella, the bacterium responsible for food poisoning, has proven particularly attractive for this purpose, as Curtiss explains: “Orally-administered RASVs stimulate all three branches of the immune system stimulating mucosal, humoral, and cellular immunity that will be protective, in this case, against a majority of pneumococcal strains causing disease.”

Recombinant Salmonella is a highly versatile vector—capable of delivering disease-causing antigens originating from viruses, bacteria and parasites.  An attenuated Salmonella vaccine against pneumonia, developed in the Curtiss lab, is currently in FDA phase 1 clinical trials.

In the current research, the team describe a method aimed at retaining the immunogenicity of an anti-pneumonia RASV while reducing or eliminating unwanted side effects sometimes associated with such vaccines, including  fever and intestinal distress. “Many of the symptoms associated with reactogenic Salmonella vaccines are consistent with known reactions to lipid A, the endotoxin component of the Salmonella lipopolysaccharide (LPS),” the the major surface membrane component , Kong explained.   “In this paper, we describe a method for detoxifying the lipid A component of LPS in living cells without compromising the ability of the vaccine to stimulate a desirable immune response.”

To achieve detoxification, Salmonella was induced to produce dephosphoylated lipid A, rendering the vaccine safer, while leaving its ability to generate a profound, system-wide immune response, intact.

To accomplish this, a recombinant strain of Salmonella was constructed using genes from another pathogen, Francisella tularensis, a bacterium associated with tularemia or rabbit fever. Salmonella expressing lipid A 1-phosphatase from tularensis (lpxE) showed less virulence in mice, yet acted to inoculate the mice against subsequent infection by wild-type Salmonella.

In further experiments, the group showed that Salmonella strains could also be constructed to additionally synthesize pneumococcal surface protein A (PspA)—a key antigen responsible for generating antibodies to pneumonia. Again, the candidate RASV displayed nearly complete dephosphorylation of lipid A, thereby reducing toxicity.

Following inoculation with the new Salmonella strain, mice produced a strong antibody response to PspA and showed greatly improved immunity to wild-type Streptococcus pneumoniae, compared with those inoculated with Salmonella lacking  the PspA antigen. Tissue culture studies showing reduction of inflammatory cytokines following application of modified lipid A further buttressed the results.

Francisella LpxE was shown to effectively strip the 1-phosphate group from Salmonella‘s lipid A, without loss of the bacterium’s capacity for colonization. The research holds promise for constructing modified live attenuated Salmonella vaccine strains for humans, with dephosphoylated lipid A providing additional safety benefits.

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The research was supported by grants from the Bill and Melinda Gates Foundation and the National Institute of Health

* Reposted on Request

Licorice licks herpes virus infection

The embargo on this press release has changed since it was originally posted

Many of the viruses that infect people can sit suppressed in cells for long periods of time, but when they are reactivated can cause painful symptoms and distress.  While treatment for active infections is progressing nicely, it remains very challenging to treat latent infections.  In particular, progress in treating herpesvirus latency has lagged behind.

Appearing in the March 1 print edition of the Journal of Clinical Investigation, Ornella Flore and colleagues from New York University School of Medicine show, for the first time, that it is possible to interfere with herpesvirus latency by inhibiting the expression of Kaposi sarcoma–associated herpes virus (KSHV) latent genes.  KSHV is the virus that is associated with Kaposi sarcoma, a disease characterized by tumors in tissues below the surface of the skin, often found in patients with immunodeficiencies like HIV and AIDS.

These investigators demonstrate that a compound found in licorice, glycyrrhizic acid (GA), can kill cells that are latently infected with KSHV. GA induces cell death by altering levels of proteins involved in latency like LANA and v-cyclin.

The possibility that GA-like compounds might be useful in treating clinical KSHV infections is of considerable interest. GA represents the first example of an anti-viral agent that specifically targets the expression of a herpesvirus gene required to maintain the virus in the latent state. The discovery of such drugs provides an opportunity for developing novel anti-herpesvirus agents to control, and perhaps eradicating latent viral infections.

In an accompanying commentary, Jeffrey Cohen states, “a compound present in licorice may seem like an unlikely candidate for the treatment of virus-associated cancers…derivates of GA might be used in the future for treating human diseases caused by latent virus infections.”

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TITLE: Glycyrrhizic acid alters of Kaposi sarcoma–associated herpesvirus latency, triggering p53-mediated apoptosis in transformed B lymphocytes

AUTHOR CONTACT: Ornella  Flore   NYU School of Medicine, New York, NY USA Phone: (212) 263-5313; Fax: (212) 263-7933; E-mail: ornella.flore@med.nyu.edu

This article is available at:  http://www.jci.org/cgi/content/full/115/3/642

ACCOMPANYING COMMENTARY:

TITLE:  Licking latency with licorice

AUTHOR CONTACT: Jeffrey I. Cohen  National Institutes Of Health, Bethesda, MD USA Phone: (301) 496-5265; Fax: (301) 496-7383; E-mail: jcohen@niaid.nih.gov

This article is available at:  http://www.jci.org/cgi/content/full/115/3/591

* Reposted for Filing

A compound from olive-pomace oil gets 80 percent slowing down of HIV spread

Contact: Professor Andrés García-Granados López de Hierro agarcia@ugr.es 34-958-243-364 University of Granada

Olive oil has become part of the fight against the Human Immunodeficiency Virus (HIV) – the cause of AIDS – thanks to the research carried out by the Bionat team, from the University of Granada, headed by Prof. Andrés García-Granados, senior lecturer in Organic Chemistry. Their work shows that maslinic acid – a natural product extracted from dry olive-pomace oil in oil mills – inhibits serin-protease, an enzyme used by HIV to release itself from the infected cell into the extracellular environment and, consequently, to spread the infection into the whole body. These scientists from Granada determined that the use of olive-pomace oil can produce an 80% slowing down in AIDS spreading in the body.

Maslinic or crataegolic acid is a pentacyclic terpene with antioxidant and anticancer effects found in wax from olive skin, alongside oleanolic acid. The effects of this compound in the fight against AIDS are simultaneously being studied in the UGR and in Hospital Carlos III in Madrid by a team headed by Prof. Vallejo Nájera.

Maslinic acid innovative properties stem from its powerful protease-inhibition activity, allowing researchers from Granada to register two patents on behalf of the UGR to produce drugs for treatment of diseases caused by protozoa Cryptosporidium – a parasite causing small intestine infection and diarrhoea – and by HIV. The University of Granada has already registered almost ten other patents related to this compound’s properties.

Maslinic acid is also a very active compound in opportunistic parasitic infections seriously affecting HIV patients.

In trials carried out by these researchers with the MT2 cell line, for concentrations of 25 and 30 µg/ml maslinic acid inhibited replication of a primary HIV-1 isolate. For 25 µg/ml a decrease in the cytopathic effect and in p24 antigen levels in the supernatant culture medium was detected. For 30 µg/ml, there was total absence of the cytopathic effect and also a decrease of p24 antigen levels.

Pilot Plant

The UGR Faculty of Sciences hosts a unique maslinic acid production pilot plant where the company MANINVEST S.L. – staffing scientists from the UGR departments of Organic Chemistry, Biochemistry and Parasitology, as well as a coordinating economist – is carrying out research on technology implementation and business programmes tuning aimed at making manitol and maslinic and oleanolic acids programmes more profitable.

Whilst manitol is obtained from olive oil waste water (alpechín) and olive-tree leaves, both acids are extracted from dry olive-pomace oil (orujo) produced at the olive-milling stage during olive oil elaboration process.

To this day, only oleanolic acid – produced in China – has been marketed. However, maslinic acid has gained importance as it is not still on the market and has a greater biological activity.

Prof. Andrés García-Granados’s team intends to continue working in the design and implementation of new maslinic acid by-products to fight against HIV, as well as in other innovative research projects financed by the Spanish Ministry of Science and Technology and the Andalusian Regional Government.

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Reference:

Prof. Andrés García-Granados López de Hierro. Department of Organic Chemistry, University of Granada.  Tel.: +34 958 24 33 64 / +34 958 24 33 20. E-mail: agarcia@ugr.es.

* Reposted before being submitted to Category

FDA Panel Members Express Opposing Views on Truvanda Approval

FDA Panel Members Express Opposing Views on Truvanda Approval

In May, the FDA Antiviral Advisory Committee met to review evidence for the approval of two antiretroviral drugs, tenofovir and emtricitabine for pre-exposure prophylaxis (PrEP) against HIV infection. Two members of the Committee explain why they voted for or against the approval. Judith Feinberg, MD, Professor of Medicine at the University of Cincinnati College of Medicine and director of the University of Cincinnati AIDS Clinical Trials Unit, serves as chairperson of the FDA Antiviral Advisory Committee. She voted in favor of the approval. She explains that while the observation period for tenofovir-emtricitabine has been short, the outcomes and tolerability have been very good. Dr. Feinberg writes that PrEP is particularly important now that HIV is on the rise among young men who have sex with men. Over the past 30 years, HIV has killed 30 million people and infected 60 million. With hundreds of millions of people still at risk, and no vaccine available, PrEP may be the strategy that helps to turn the tide on HIV. Lauren V. Wood, MD, Staff Clinician at the National Cancer Institute and Assistant Professor at the Uniformed Services University of the Health Sciences is also a member of the FDA Antiviral Advisory Committee. Dr. Wood voted against the approval for several reasons. First, Dr. Wood did not find consistent evidence of the benefit of PrEP, especially in women. Second, she expressed concern about low rate of adherence to the tenofovir-emtricitabine regimen. Since adherence is crucial to efficacy, she could not support approval. And finally, Dr. Wood cited safety concerns about PrEP dosing. And since no long-term studies have been done, the potential for the emergence and spread of drug resistant virus as a consequence of PrEP remains a concern

The U.S. Global Fund for Aids Transfers 100’s of Millions of USD to the Russian and Chinese Governments

After this Global Aids Day Conference,  I  noticed  large  sums  of money going into the “U.S. President’s Emergency Plan for AIDS Relief”   http://www.pepfar.gov . There are two Red Flags that need cleaning up.

  1. In order to determine which companies are profiting from this U.S. Government charitable  organization. We would need to go to see who the Donor list is….
  2. So we follow the link Contributions to the Global Fund: http://www.pepfar.gov/coop/globalfund/contributions/index.htm
  3. Then we click on the list: http://www.theglobalfund.org/en/resources/?lang=en
  4. At this point in  time we have a broken link. Which I find surprising with all these public commitments to donate.

Next Let us see who is actually getting the Grant Money:

For this we go to:

Download Grant Data

http://portfolio.theglobalfund.org/en/DataDownloads/Index

Then from there we go to:

Individual Disbursements

http://www.theglobalfund.org/documents/core/grants/Core_DisbursementDetails_Report_en/

While there are some worthy organizations receiving grant money.

I would like you to take notice of the 100’s of millions of USD going to Russian and China…. Countries in far better financial shape than the U.S.

I am not here to speculate, nor form a hypothesis. All I see is an Inconsistency that requires clarification

* Keep in mind the U.S. is the largest Contributor to the Global Fund..Even though we can’t find the documentation, it is through their verbal statements..

Ralph Turchiano