Tag Archives: medicine

Scientists Have Found A Way To Make Cells Resistant To HIV

TSRI Senior Staff Scientist Jia Xie was first author of the new study. (Photo by Madeline McCurry-Schmidt.)

In a remarkable step forward in the potential treatment of HIV, scientists in California have successfully created a cell population that is resistant to the disease.

The new approach, described as a form of “cellular vaccination” aims to offer long-term protection for patients by tethering HIV-fighting antibodies to their immune cells.

Jia Xie, senior staff scientist, said: “The ultimate goal will be the control of HIV in patients with AIDS without the need for other medications,” as even with antiretroviral drug treatments, people with HIV still suffer much higher incidences of cancer and other deadly diseases.

Here, cells protected from rhinovirus by membrane-tethered, receptor-blocking antibodies survive well and form colonies. Credit: Jia Xie, Lerner Lab

Joseph Alvarnas who was involved in the study, said: “HIV is treatable but not curable – this remains a disease that causes a lot of suffering. That makes the case for why these technologies are so important.”

The new technique is superior to therapies where antibodies float freely in the bloodstream at a relatively low concentration, as the antibodies hang on to the cell’s surface blocking HIV from accessing a crucial receptor and spreading infection.

Known as the ‘neighbour effect’ the team showed that resistant cells could quickly replace diseased cells, potentially curing a person of HIV through gradual displacement.

Xie said: “You don’t need to have so many molecules on one cell to be effective.”

In essence, the researchers had forced the cells to compete in Darwinian ‘survival-of-the-fittest’ selection in a lab dish. Cells without antibody protection died off, leaving protected cells to survive and multiply, passing on the protective gene to new cells.

To infect a person, all strains of HIV need to bind with a cell surface receptor called CD4, so the team at the Scripps Research Institute and City of Hope research centre near Los Angeles, tested antibodies that could potentially protect this receptor on the very immune cells normally killed by HIV.

The antibodies recognized the CD4 binding site, blocking HIV from getting to the receptor.

The next step in this research is to try engineering antibodies to protect a different receptor on the cell surface, according to Xie.

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HIV in Gaza: “I know, so I am not afraid”

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Fifty-year-old Um Mohammad, a mother of nine, has been living with HIV for 16 years in the Gaza Strip in the occupied Palestinian territory. She was nursing her baby girl when tests revealed she was HIV positive.

“We found out that I got the HIV while I was still breastfeeding my youngest. I got it from my husband,” she says. “I was scared for my baby girl, but thank God, it was not transmitted to her. I was so relieved.”

Um Mohammad spoke at a training workshop for journalists in Gaza organized by the UNDP Programme of Assistance to the Palestinian People with financial support from the Global Fund to fight HIV/AIDS, Tuberculosis and Malaria (the Global Fund). The training aimed at reducing stigma and provided accurate messages and facts on HIV.

According to the Ministry of Health in the occupied Palestinian territory, the cumulative number of patients with HIV and AIDS since 1987 has reached 72 cases, although problems with under-reporting and HIV surveillance systems means that accurate statistics in the Arab region are difficult to come by.

This is particularly true in Gaza. Out of 29 known cases of people living with HIV recorded in the Gaza Strip as per available statistics, only eight people are still alive and currently receiving antiretroviral (ARV) treatment and support through the UNDP-managed Global Fund programme. In the occupied Palestinian territory as a whole, 21 people with advanced HIV are receiving treatment and 20 persons living with HIV are provided psychosocial support.

The programme also includes critical awareness-raising sessions and stigma reduction activities with a special focus on religious leaders, the media and legal aid professionals. More than 2,000 people in the occupied Palestinian territory have received critical HIV testing and counselling sessions, including Um Mohammad.

“Many people are not aware how of HIV is transmitted”, she explains. HIV is transmitted through unprotected sex, transfusion of contaminated blood or from the use of non-sterile injecting equipment.

“I know, so I am not afraid,” she says. “I am able to share with my children their food and utensils and I kiss them good night like every mother. I do the same with my neighbours and relatives.”

Um Mohammad’s husband died four months after he was diagnosed with AIDS and she was left to provide for her family. “I became the mother and father of my nine children,” she says. “I brought them up the best way I can.”

UNDP is the Principal Recipient for Global Fund programmes in a number of countries. In the occupied Palestinian territory, working closely with the Ministry of Health and UN agencies, the Global Fund-supported HIV-programme has significantly contributed to preventing the spread of HIV, as well as to providing treatment and care services to persons living with HIV and AIDS.

The Global Fund has committed US$11 million to the project over a five year period (2009-2013). Today, thanks to the initiative’s efforts, 22 non-governmental organizations are providing HIV and AIDS prevention, awareness and support services in the Gaza Strip and West Bank.

“It is time now for our society to treat people living with HIV and AIDS like any person who has the right to live, work, learn and receive treatment when sick,” Um Mohammad says.

by Amar Bokhari, Reem Abu Shomar and Dania Darwish at the United Nations Development Programme (Link)

 All names in this article have been changed to protect the privacy of those involved

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Human Genome Tinkering Could Be Our Best Bet to Beat HIV

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The human immunodeficiency virus (HIV) is a crafty little beast, constantly mutating to mask itself from our body’s defenses, but always entering cells through the same molecular door. The design of that cellular door is governed by our DNA, so why not change the lock by modding our genetic code?

In 2006, a minor medical miracle occurred. HIV-positive leukemia patient Timothy Ray Brown—the second Berlin Patient—received a bone marrow transplant that saved his life in more ways than one. The marrow that he received was from a donor with a unique double mutation to a gene on the 3rd chromosome known as CCR5. This gene codes for the surface protein that the HIV virus uses to gain entry into our white blood cells (specifically, CD4+ T-cells); however the double mutation shuts down these sites and provides a natural immunity to HIV. This mutation is exceptionally rare, only occurring in about one percent of Caucasians and nowhere else. It’s been hypothesized that it’s this same natural immunity that allowed a small portion of Europeans to make it through the Black Plague unscathed.

While that was fantastic news for Brown, who nearly a decade later remains off of his retroviral drug regimen and maintains an undetectable level of the virus in his system, it’s not of much use to the rest of us. With both the mutation prevalence and bone marrow compatibility matches in general being so rare, there was no effective means of using transplants as delivery vectors for this beneficial genetic condition. And it’s worth noting that the very process of becoming HIV-free nearly killed Brown. But that’s where Professor Yuet Kan’s team at UCSF comes in.

Kan figured that if integrating this double mutation wouldn’t work on the macro level—that is, replacing a patient’s bone marrow with that of a naturally HIV-immune person’s—maybe it would at the molecular level, thereby allowing researchers to confer the benefits while cutting out the marrow donation. To that end, he and a team of researchers from the University of San Francisco are employing cutting-edge genetic editing techniques to snip out the beneficial length of DNA coding and integrate it with a patient’s own genome.

The technique they’re using is known as CRISPR (Cas9) genome-editing. CRISPRs, (clustered regularly interspaced short palindromic repeats) are DNA delivery vectors that replace the existing base codes at a specific part of a specific chromosome with new base pair sets. Cas9, on the other hand are the “molecular scissors” that Kan’s team employs to first cut out the offending DNA. It sounds easy, sure—just find the string of DNA you want to replace, then snip it out with Cas9 DNA scissors, and install some new DNA using a CRISPR—however the nuts and bolts of the process are far more technically challenging.

The patient’s own blood cells would be employed as a precursor. Researchers would then have to convert those cells into induced pluripotent stem (iPS) cells by modulating a number of genetic switches, thereby instigating their regression to more basic stem cells. After that, the offending CCR5 gene would need to be knocked out and replaced with the better, double-mutated version before the now fortified blood cells were transfused back into the patient. Not only is there no chance of the body rejecting the new cells (they are the patient’s own after all), the technique also neatly sidesteps the whole embryonic stem cell issue.

While the technique is still in its early stages of development and no human trial dates have yet been set, it holds huge promise. Not just for the 35 million people annually infected by HIV, but also sufferers of sickle cell anemia and cystic fibrosis—two deadly diseases caused by a single protein deformation—could benefit from similar techniques. By figuring out which genes do what on our iPS cells, we could even theoretically grant everyone on Earth immediate immunity to any number of diseases.

Of course, being able to update and augment our genetic code opens up a whole slew of potential concerns, objections, and abuses. Just look at the ire raised over the use of embryonic stem cells in the early 2000s. People were lost their minds because they thought scientific progress was being built on the backs of fetuses. Researchers had to go and invent an entirely new way of making stem cells (the iPS lines) just to get around that one moralized sticking point, so you can bet there will be plenty of chimera, master race, and Island of Dr. Moreaureferences bandied about should we ever begin seriously discussing the prospect of upgrading our genes. And could certainly slow progress in this specific research.

That’s not to say that the hysteria that accompanies seemingly every news cycle these days is completely off base. Like cars, styrofoam, pressure cookers, and thermonuclear bombs, this technology can be used for evil just as easily as it can be for good. And while we’re not nearly as genetically complex as, say, an ear of corn, wrangling the myriad of interactions between our various genes is still an incredibly complex task and one with severe consequences should something go awry—even if we can avoid creating unwanted mutations through stringent testing and development methodology as we do with today’s pharmaceutical development. So why not turn ourselves into the ultimate GMOs? It certainly beats everyone becoming cyborgs.

Article via Gizmodo

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Admare Jinga sentenced for ‘HIV cure’ fraud

Jinga, Admare

Admare Jinga, 31, was sentenced at Belfast Magistrates Court on Tuesday

A man who was convicted of an on-line scam selling products that claimed to ‘kill’ the HIV virus has been sentenced to 240 hours community service.

Admare Jinga used his base in Belfast to set up a company that advertised and distributed products overseas, particularly to his native Zimbabwe.

In June, he was found guilty of fraud by false representation.  He had already admitted a second charge of marketing medicines for human use without proper authorisation.

The 31-year-old University of Ulster graduate was sentenced at Belfast Magistrates Court on Tuesday.
Jinga, who now lives in Hamilton, Lanarkshire, Scotland, will carry out his community service over the next 12 months.  During the trial, Belfast Magistrates Court had heard that Jinga established a company called Savec Healthcare Ltd in 2007, when he was living in south Belfast.

Up until 2009 it marketed products as alternative forms of treatment for the HIV infection.  They claimed to be able to kill, prevent or stop Aids, according to the prosecution.

In the witness box Jinga said he became involved with pharmacists, a microbiologist and other Zimbabwean professionals concerned with the impact of HIV in their country.  Jinga claimed that no complaints were ever received from people who used his products.
The case against him was taken by the Medicines and Healthcare Products Regulatory Agency (MHRA).  In a statement issued after the sentencing, the MHRA said the case was its first ever prosecution of its kind.

The agency said it took action against Jinga after he was found to be selling a machine and accompanying medicine over the internet that he falsely claimed could cure HIV and Aids.

“There are no known cures for HIV so any claim to this effect is illegal,” the MHRA statement added.

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Are you interested in news and articles about genuine research into developing a cure for HIV? – We have some articles for you to read, take a look at these:

Anti-HIV drug effort in South Africa yields dramatic results

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An intensive campaign to combat HIV/AIDS with costly antiretroviral drugs in rural South Africa has increased life expectancy by more than 11 years and significantly reduced the risk of infection for healthy individuals, according to new research.

The two studies, published Thursday in the journal Science, come as wealthy Western nations are debating how best to stretch limited AIDS funding at a time of economic stress.

With an annual price tag of $500 to $900 per patient, antiretroviral therapy programs have stirred frequent debate. Critics argue that adherence to the drug regimen is low and social stigma prevents some from seeking care until they are very ill and have infected others. Cheaper remedies, such as condom distribution, male circumcision and behavior modification, deserve more attention and funding, they say.

The new economic analysis of a $10.8-million campaign in KwaZulu-Natal province concluded that the drug scale-up there had been highly cost-effective.

The program was administered by nurses in rural health clinics in an impoverished region of about 100,000 people. Treatment consisted primarily of daily doses of antiretroviral therapy, or ART, drugs, which patients take every day for their entire lives. Patients picked up their medication at a rural clinic once a month.

In 2003, the year before the drugs were available, 29% of all residents were infected with HIV and half of all deaths there were caused by AIDS. Life expectancy in the region was just over 49 years.

By 2011, life expectancy had grown to 60 1/2 years — “the most rapid life expectancy gains observed in the history of public health,” said study senior author Till Barnighausen, a global health professor at the Harvard School of Public Health.

Based on that increase in longevity, researchers determined just how many years of life were effectively “gained” among residents as a result of ART intervention. They used that figure and the total expense of the program to calculate a cost-effectiveness ratio of $1,593 per life-year saved.

The World Health Organization considers medical intervention to be “highly cost-effective” if the cost per year of life saved is less than a nation’s per capita gross domestic product. The program’s ratio was well below South Africa’s 2011 per capita GDP of about $11,000.

“It’s really a slam dunk of an intervention,” said study leader Jacob Bor, a graduate student at Harvard. “These investments are worthwhile.”

The research team noted that the study period coincided with the arrival of electric power and clean water for area residents. But those alone could not explain the dramatic increase in longevity, they said.

“While mortality due to HIV declined precipitously, mortality due to other causes flat-lined,” Bor said. “These changes were almost certainly due to ART scale-up.”

In a second study from the same region, researchers followed nearly 17,000 healthy people from 2004 to 2011 to determine HIV infection rates in areas with active ART intervention programs.

Healthy individuals in those areas were 38% less likely to contract HIV than people in areas where ART drugs were not widely available, researchers found. People in extremely rural areas also fared better than those in more closely populated areas clustered around national roads.

Overall HIV prevalence increased 6% during the seven years of the study, probably because the antiretroviral drugs allowed people with the virus to live longer, according to the report.

It’s not clear how the results of the new study would translate to areas where stable, cohabiting couples were not the norm, said lead author Frank Tanser, an epidemiologist at the University of KwaZulu-Natal.

AIDS researchers who weren’t involved in the studies said they provide strong support for maintaining programs like the President’s Emergency Plan for AIDS Relief, begun by President George W. Bush in 2003.

“These papers present truly remarkable data,” said Dr. Douglas Richman, director of the Center for AIDS Research at UC San Diego.

Original article via Gawker

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A Cure for HIV/AIDS Has Got a Step Closer!

Listen to this article instead [audio http://www.lass.org.uk/files/uploads/120802.mp3]

HIV is an exceptional adversary. It is more diverse than any other virus, and it attacks the very immune cells that are meant to destroy it. If that wasn’t bad enough, it also has a stealth mode. The virus can smuggle its genes into those of long-lived white blood cells, and lie dormant for years. This “latent” form doesn’t cause disease, but it’s also invisible to the immune system and to anti-HIV drugs.

When the virus awakens, it can trigger new bouts of infection – a risk that forces HIV patients to stay on treatments for life. It’s clear that if we’re going to cure HIV for good, we need some way of rousing these dormant viruses from their rest and eliminating them.

Now, a cure for HIV/AIDS has got a step closer after scientists found that a common cancer drug can purge the disease as it lies dormant in the body.  Current treatments are effective at reducing levels of the disease in the bloodstream – but a drug that can ‘knock out’ the disease when it lies dormant is thought to be key to a cure.

A team of US scientists led by David Margolis has found that vorinostat – a drug used to treat lymphoma – can do exactly that. It shocks HIV out of hiding. While other chemicals have disrupted dormant HIV within cells in a dish, this is the first time that any substance has done the same thing in actual people.

At this stage, Margolis’s study just proves the concept – it shows that disrupting HIV’s dormancy is possible, but not what happens afterwards. The idea is that the awakened viruses would either kill the cell, or alert the immune system to do the job. Drugs could then stop the fresh viruses from infecting healthy cells. If all the hidden viruses could be activated, it should be possible to completely drain the reservoir. For now, that’s still a very big if, but Margolis’s study is a step in the right direction.

HIV enters its dormant state by convincing our cells to hide its genes. It recruits an enzyme called histone deacetylase (HDAC), which ensures that its genes are tightly wrapped and cannot be activated. Vorinostat, however, is an HDAC inhibitor – it stops the enzyme from doing its job, and opens up the genes that it hides.

It had already proven its worth against HIV in the lab. Back in 2009, three groups of scientists(including Margolis’ team) showed that vorinostat could shock HIV out of cultured cells, producing detectable levels of viruses when they weren’t any before.

To see if the drug could do the same for patients, the team extracted white blood cells from 16 people with HIV, purified the “resting CD4 T-cells” that the virus hides in, and exposed them to vorinostat. Eleven of the patients showed higher levels of HIV RNA (the DNA-like molecule that encodes HIV’s genes) – a sign that the virus had woken up.

Eight of these patients agreed to take part in the next phase. Margolis gave them a low 200 milligram dose of vorinostat to check that they could tolerate it, followed by a higher 400 milligram dose a few weeks later. Within just six hours, he found that the level of viral RNA in their T-cells had gone up by almost 5 times.

These results are enough to raise a smile, if not an outright cheer. We still don’t know how extensively vorinostat can smoke HIV out of hiding, or what happens to the infected cells once this happens. At the doses used in the study, the amount of RNA might have gone up, but the number of actual viral particles in the patients’ blood did not. It’s unlikely that the drug made much of a dent on the reservoir of hidden viruses, so what dose should we use, and over what time?

Vorinostat’s actions were also very varied. It did nothing for 5 of the original 16 patients. For the 8 who actually got the drug, some produced 10 times as much viral RNA, while others had just 1.5 times more. And as you might expect, vorinostat comes with a host of side effects, and there are concerns that it could damage DNA. This study could be a jumping point for creating safer versions of the drug that are specifically designed to awaken latent HIV, but even then, you would still be trying to use potentially toxic drugs to cure a long-term disease that isn’t currently showing its face. The ethics of doing that aren’t clear.

Steven Deeks, a HIV researcher from the University of California San Francisco, talks about these problems and more in an editorial that accompanies the new paper. But he also says that the importance of the study “cannot be over­stated, as it provides a rationale for an entirely new approach to the management of HIV infection”.

Progress is being made every day, don’t believe us? – Check out the related articles below!

Original Articles via Discover Magazine and Mail Online

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Even without a cure, the end of the AIDS pandemic is in sight

A very bold statement to make in the run up to AIDS 2012, none the less, this is the view of Dr. Anthony Fauci, director of the National Institute of Allergy and Infections Diseases (NIAID )

NIAID director Dr. Anthony Fauci addressing the United Nations General Assembly special session on HIV/AIDS on 10June 2008.

Dr. Fauci was appointed Director of NIAID in 1984. He oversees an extensive research portfolio of basic and applied research to prevent, diagnose, and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.  Dr. Fauci serves as one of the key advisors to the White House and Department of Health and Human Services on global AIDS issues, and on initiatives to bolster medical and public health preparedness against emerging infectious disease threats such as pandemic influenza.

Dr. Fauci has made many contributions to basic and clinical research on the pathogenesis and treatment of immune-mediated and infectious diseases. He has pioneered the field of human immunoregulation by making a number of basic scientific observations that serve as the basis for current understanding of the regulation of the human immune response. In addition, Dr. Fauci is widely recognized for delineating the precise mechanisms whereby immunosuppressive agents modulate the human immune response. He has developed effective therapies for formerly fatal inflammatory and immune-mediated diseases such as polyarteritis nodosa, Wegener’s granulomatosis, and lymphomatoid granulomatosis. A 1985 Stanford University Arthritis Center Survey of the American Rheumatism Association membership ranked the work of Dr. Fauci on the treatment of polyarteritis nodosa and Wegener’s granulomatosis as one of the most important advances in patient management in rheumatology over the previous 20 years.

AN END TO NEW INFECTIONS?

Three decades into the AIDS pandemic an end to new infections is in sight, according to Dr. Fauci.

“We don’t even know if a cure is possible. What we know is it is possible that we can end this pandemic even without a cure,”

Fauci told AFP in an interview ahead of the International AIDS conference 22nd -27th July in Washington DC, America.

Some 34 million people around the world are living with human immunodeficiency virus, which has killed 25 million since it first emerged in the 1980s.

The theme of this conference, which is held every two years, is “Turning the Tide Together,” and is based on experts sharing knowledge of the latest advances and how to best implement them in order to halt new cases of HIV/AIDS.

“We have good and effective treatments but we have to keep people on the treatments indefinitely in order to keep them well,” said Dr. Fauci, referring to antiretroviral drugs which have transformed a deadly disease into a manageable condition.

“When you have a very marked diminution of the number of new infections then you reach what we call and AIDS-free generation.”

Dr. Fauci said he did not expect any staggering breakthroughs to be announced at the conference, but that the gain would come though collaborating on ideas to speed progress by using the tools that practitioners have already at hand.

Otherwise, if progress continues at the present rate of reducing new infections worldwide by about 1.5 percent per year, the goal becomes too distant, he said.

Recent studies that tested antiretroviral drugs in healthy people as a way to prevent getting HIV through sex with infected partners have shown some promise, though getting people to take their medication daily had proven a challenge.

“The important thing is you have to take your medication,” Fauci said, noting that average HIV risk reduction in a study of men who have sex with men was just 44 percent.

The approach of treating healthy people with antiretrovirals is known as pre-exposure prophylaxis, and “is not for everyone,” Fauci said. “We have to selectively use it.”

The US Food and Drug Administration on Monday approved the first pill for HIV prevention, Truvada, despite concerns by some in the health care community that it could encourage drug resistance and risky sex.

Novel ways to boost testing are also good news, particularly with the recent US approval of the first at-home HIV test.

“It is so important in the quest to ending the AIDS pandemic to get as many people tested as possible. You can link them to care and get them on treatment. Anything that makes that goal easier would be an important advance.”

As far as an AIDS vaccine, Fauci said researchers have made “good progress” but “still have a long way to go.”

Experts are examining a trial done in Thailand that showed in 2009 modest efficacy of just over 30 percent, but is still considered a breakthrough and offers clues for future study into why some were helped and others were not.

Dr. Fauci also said he did not expect much concern to be raised over upcoming reports of the extent of drug resistance to antiretrovirals.

“People may think I am taking it lightly but quite frankly it is not a serious problem,” Fauci said.

He added that overall, AIDS research is “going well” even though “funding is restricted right now.”

And he expressed pride in the United States’ President’s Emergency Plan for AIDS Relief (PEPFAR), “which has really transformed how you can get people in low income countries to get on treatment care and prevention.”

The United States provides almost half the world’s funding for international HIV assistance, according to UNAIDS.

The International AIDS Conference is returning to the United States after more than two decades away due to a ban on travel and immigration by people with HIV that was lifted in 2008 and signed into law in 2009.

Fauci called those restrictive laws “unfortunate” and “embarrassing.”

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