Tag Archives: International AIDS Society

MH17: HIV community mourns loss of pioneer researcher Joep Lange

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The international AIDS community is mourning the deaths of researchers whose plane was shot down over Ukraine and who were travelling to Melbourne for a global AIDS conference.

The former International AIDS Society president Joep Lange and his partner and ArtAids board member Jacqueline van Tongeren have been confirmed as having been on the flight, while there are reports of others including a World Health Organization spokesman, Glenn Thomas.

298 people – 283 passengers including three infants and 15 crew – were killed on the Malaysia Airlines flight 17.

Global leaders mourned

David Cooper, director of the Kirby Institute at UNSW Australia, was a friend of Joep Lange. He received a call at 3am telling him that Lange and his partner were on the flight.

Professor Cooper said his colleague of 30 years had “an absolute commitment to HIV treatment and care in Asia and Africa”.

“Joep was absolutely committed to the development of affordable HIV treatments, particularly combination therapies, for use in resource-poor countries,” Professor Cooper said.

Professor Lange was a professor of medicine and head of the Department of Global Health at the Academic Medical Centre at the University of Amsterdam. He served as president of the International AIDS Society from 2002 to 2004.

In his 30 years of researching HIV, he led pivotal trials of antiretroviral therapy and published more than 350 papers in peer-reviewed journals.

“Another outstanding area of [Lange’s] contribution has been his pioneering role in exploring affordable and simple antiretroviral drug regimens for the prevention of mother-to-child transmission of HIV in resource-poor settings,” Professor Cooper said.

“Both of these have been part of his dedication to increasing access to effective HIV treatment.  The joy in collaborating with Joep was that he would always bring a fresh view, a unique take on things, and he never accepted that something was impossible to achieve.”

More AIDS2014 delegates feared lost

Australia’s Foreign Minister Julie Bishop has told reporters this morning: “A number of people who were travelling to Malaysia for an international AIDS conference were also on board”.

The Malaysia Airlines flight MH17 from Amsterdam to Kuala Lumpur was due to connect with a flight to Perth, before people travelled onto Melbourne, Reuters and others have reported.

UNAIDS director Michael Sidibe, who is already in Melbourne for the week-long 20th International Aids Conference, tweeted: “Many passengers were enroute to #AIDS2014 here in #Melbourne.”

The conference organisers, the International AIDS Society, released a statement expressing “sincere sadness” at the news of the M17 disaster:

At this incredibly sad and sensitive time the IAS stands with our international family and sends condolences to the loved ones of those who have been lost to this tragedy.

Story via The Conversation

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Prominent HIV researcher Joep Lange was among the victims of flight MH17

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Joep Lange, a prominent HIV researcher and former president of the International AIDS Society, was one of the victims of Malaysia Airlines flight MH17.

A professor of medicine and head of the department of global health at the University of Amsterdam, Lange had been involved in HIV treatment and research since 1983, just as the virus was emerging as a global health threat.

He was one of the key researchers behind several pivotal antiretroviral therapy trials, including projects involving the prevention of mother-to-child transmission of the virus, according to the Amsterdam Institute of Global Health and Development.

Lange was on his way to AIDS 2014, a global conference that will take place in Melbourne, Australia from July 20 to 25, at the time of death.

He was traveling with his wife, who has also died in the crash.

“Joep was a visionary amongst HIV researchers,” American HIV researcher Dr. Rick Elion told Vox. “He was acutely aware of the multiple dimensions of HIV spanning science to society and had a heart of gold. This is a huge loss for the field.”

“Joep was absolutely committed to the development of affordable HIV treatments, particularly combination therapies, for use in resource-poor countries,” David Cooper, a friend and fellow researcher told the Australian academic news website The Conversation.

“Another outstanding area of [Lange’s] contribution has been his pioneering role in exploring affordable and simple antiretroviral drug regimens for the prevention of mother-to-child transmission of HIV in resource-poor settings,” Cooper said.

Other researchers and activists have died en route to the AIDS conference, though the death toll has not yet been confirmed.

Australian newspapers are reporting that as many as 108 conference participants may have been on the plane.

The International AIDS Society issued a statement on the losses:

The IAS today expresses its sincere sadness at receiving news that a number of colleagues and friends en route to attend the 20th International AIDS Conference taking place in Melbourne, Australia, were on board the Malaysian Airlines MH17 flight that has crashed over Ukraine earlier today.

At this incredibly sad and sensitive time the IAS stands with our international family and sends condolences to the loved ones of those who have been lost to this tragedy.

We also at LASS, recognise this incredible loss of some some of the worlds finest scientific HIV activists and send our sympathies and heartfelt sorrow to the families of those who died yesterday on flight MH17.

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No Hiding Place for HIV/AIDS

HIV/AIDS researchers, many of whom met last month under the auspices of the International AIDS Society, are rightly pleased with the progress they have made. In particular, the use of antiretroviral drugs has not only revolutionised treatment of HIV infection, but also offers the prospect of stopping the spread of the virus. In a matter of weeks, these drugs reduce the number of viruses per millilitre of infected blood from millions to less than 50.  That deals with both symptoms and infectivity. Unless a patient stops taking the drugs, or goes on to develop resistance to them, he can expect to live almost as long as an uninfected individual.

But good as they are at keeping viral levels low, antiretrovirals never destroy the virus completely and thus cure the patient once and for all. There are two reasons. One is that, although HIV reproduces mainly in immune-system cells called T-cells, it also lives in certain cells of the brain, gut and lymph nodes. In these cells it is protected from the drugs by mechanisms that are, as yet, not fully understood. The other is that even in T-cells it sometimes stops replicating and becomes dormant. Since antiretrovirals work by interfering with the process of replication, dormant viruses are immune to their effects. Take the drugs away, and when a dormant virus wakes up again it will rapidly reinfect the body it is in.

The search for a cure for HIV/AIDS, then, has led only to frustration. And calls by the conference’s organisers to renew that search might be regarded by old hands as little more than platitudes. But they are not, for there is a glimmer of hope on the horizon. To deal with dormant viruses several researchers are taking what sounds like a counter-intuitive approach. They are trying to wake the viruses up and so boost, rather than reduce, the amount of active HIV in a patient’s body. Their reasoning is that the now-active viruses will either kill the cells they are in (and thus themselves) or encourage the immune system to attack those cells.

Wake-up call and the purging croton

One drug that promises to do this is interleukin-7. This substance, which is being tested in several clinical trials in America, occurs naturally in the body and in normal conditions encourages the proliferation of the T-cells that HIV invades. One of the causes of viral dormancy is that the T-cell the virus resides in is itself in a resting state. Such cells on sabbatical do not churn out many proteins of their own, so the virus cannot hijack the protein-manufacturing process—which is how it reproduces.

The idea is that a dose of interleukin-7 will nudge the T-cell—and therefore the virus—into wakefulness. And it seems to work. Robert Murphy of Northwestern University, in Illinois, who is leading one of the clinical trials, says blips of reawakened virus can indeed be seen in patients’ blood after a dose of interleukin-7. Whether subsequent treatment with antiretrovirals can then cleanse the immune system completely remains to be seen. But this is a promising start.

An alternative approach is to activate the virus directly, rather than activating the cell it is living in. This is a way of dealing with the second cause of HIV inactivation. The virus must copy its genes into the host cells’ chromosomes before these genes can be used. And sometimes, those genes become so tightly packed away within their host chromosome that they cannot be read by the cell’s DNA-transcription mechanism. To be activated they must be liberated from the chromosomal coils.

A group of agents called histone deacetylase inhibitors can help here, says Sharon Lewin, director of the infectious-diseases unit at Alfred Hospital in Melbourne, who is about to start a clinical trial of a histone-deacetylase inhibitor called SAHA. Histones are proteins that regulate DNA packing, and histone deacetylases are enzymes that control the way those proteins work. One of their effects is to keep HIV genes switched off. So inhibiting their activity should switch those genes back on.

Until now, SAHA has been tested only in cell cultures. These tests have found that it increases the expression of dormant HIV genes fivefold. Combining it with other agents, in particular one called prostratin, makes it even more effective—at least, in a Petri dish. Prostratin is thought to activate a protein that promotes replication of the virus. In a study led by David Schaffer and Adam Arkin of the University of California, Berkeley, around 80% of latent HIV became active in cell cultures treated with a combination of SAHA and prostratin. Preliminary research suggests that prostratin may also prevent copies of the purged virus which are circulating in the bloodstream from integrating themselves back into healthy immune cells.

More powerful variants of prostratin are now in the offing. In the past, the substance has been extracted directly from plants, and was available only in small quantities. In 2008, however, Paul Wender of Stanford University found a way of synthesising it from the oil of the purging croton plant, which is abundant, and he has gone on to create tweaked versions of the molecule that, he claims, are 1,000 times more potent than prostratin.

Although none of the studies published so far has managed to reactivate all of the dormant HIV in either a cell culture or a human being, they are still an encouraging step. And Dr Schaffer and Dr Arkin suspect that complete reactivation may not be necessary. If the new treatments miss latent copies of the virus that are hard to activate, then those copies may, in any case, pose less of a risk of reactivating and replicating naturally, because they are in a deeper state of dormancy.

Unfortunately, none of these drugs deals with the other part of the problem: the viruses in the brain, gut and lymph nodes. But many workers in the field think T-cell dormancy a more significant cause of relapse than HIV in such reservoir tissues. If it can be dealt with, that will be a huge step towards the ultimate desideratum of HIV research—a simple and effective cure.

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