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AIDS Care Gap Between Wealthy And Developing Countries Risks Becoming A Chasm

January 26, 2011

AIDS leaders gathering in London today face the daunting challenge of implementing new World Health Organization (WHO) recommendations for earlier treatment with better AIDS drug cocktails at a time when donors are backing away from the promise of "universal access," said Doctors Without Borders/Médecins Sans Frontières (MSF).

The WHO recently released new treatment recommendations for people living with HIV in developing countries which could help bridge the significant gap between the standard of care for people in northern and southern countries.

"In MSF programs we are striving to meet the higher standard of care which means starting patients on antiretroviral drugs earlier, which gives them a better chance of long-term survival," said Ariane Bauernfeind, program manager at MSF in Brussels. "I look forward to the day when I no longer have to see patients experiencing the painful and debilitating side effects of the drug stavudine (d4t). WHO recommends replacing stavudine with other drugs. However, we see ministries of health hesitating to make these changes because of a withdrawal of donor commitments."

Lesotho, the poorest among the countries most affected by HIV, has already updated its national protocols in 2008 recognizing the clinical and financial benefits of improved care. MSF is working with the Ministry of Health in rural areas to provide the optimal package of HIV/AIDS treatment, including an early start on a tenofovir-based regimen.

Changing towards the improved WHO guidelines will cost more in the short term, but long term it is necessary for ensuring better survival and greater control of the epidemic.

"If WHO's new recommendations are not implemented, the international community risks subsidizing less expensive yet sub-standard care for developing countries," said Sharonann Lynch, MSF's HIV/AIDS policy advisor. "Avoiding this will depend on the willingness of donors to make new commitments. Although this is not easy in today's financial environment, donor countries cannot back away from supporting the promise of universal access to treatment made five years ago."

In 2005 the G8 committed to supporting AIDS treatment for everyone who needed it by 2010. But today WHO estimates that only four of 14 million people needing AIDS treatment have access to it. Many African countries facing crushing epidemics depend on external funding to sustain and scale up HIV treatment programs. But the commitment of funders is waning. The United States President's Emergency Plan for AIDS Relief (PEPFAR) has kept funding flat over the past few years and scaled back financial commitment for treatment slots in some countries. Shifting donor priorities have also rendered uncertain the future support from the Global Fund to Fight HIV/AIDS, TB and Malaria. The Global Fund which has thus far paid for two thirds of the people who are currently receiving HIV/AIDS treatment needs to raise at least US$20 billion for the next three years of programs.

Because of this funding retreat, some facilities are facing the stark reality of rationed treatment slots and need to turn away patients from clinics.

As an emergency medical humanitarian organization, MSF has provided life-saving HIV/AIDS treatment for over 140,000 people in over 30 countries.

Doctors Without Borders/Médecins Sans Frontières

New Clues to Inflammatory Disease Discovered

January 11, 2011

Immune system cells called macrophages spring into action to surround and destroy threats such as viruses or cancer cells. But sometimes the would-be protective response leads to persistent inflammation, which, in turn, can cause disease.

Scientists don't know exactly how macrophages cross the line from being good cops to bad cops, but researchers at the University of Florida recently unearthed several clues about the mechanisms involved. Through the lens of two inflammation-related diseases, HIV and rheumatoid arthritis, they identified changes in specific proteins linked to the action of macrophages, white blood cells that are key to the body's natural defenses.

The findings could lead to new early diagnosis tools and targeted therapy for diseases that stem from abnormal or uncontrolled macrophage activation, including cancer, cardiovascular disease and neurological disorders.

"Macrophage activation is important because it is involved in inflammation, which is involved in a number of diseases," said molecular biologist Maureen Goodenow, Ph.D., the Stephany W. Holloway university chair in AIDS research and professor of pathology, immunology and laboratory medicine in the UF College of Medicine, who led the research. "Chronically inflamed macrophages can be a problem for human health."

The findings, published in April and June in the journals AIDS and Cellular Immunology, built on studies also published in April by the group in the Journal of Leukocyte Biology.

With the advent of powerful antiretroviral therapies, people infected with HIV now survive for decades without progressing to AIDS. Even so, they battle inflammatory conditions such as HIV-associated dementia and cardiovascular disease.

One cause of macrophage activation that researchers are exploring is microbial translocation -- the spilling of parts of intestinal microbes into the blood circulation. Researchers have proposed that bacterial products thus released can activate immune system T cells and in so doing lead to the progression to AIDS.

One of those pathogen-related proteins spilled into the blood is called LPS. In studies of plasma and blood cells from people infected with HIV, the UF team investigated whether the amount of the protein present was associated with how quickly HIV progressed to AIDS. They found no correlation between the protein levels and depletion of T cells, the hallmark indicator of AIDS. Instead, they found that it was associated with activation of macrophages and their precursor cells, and with inflammation that persisted even after anti-viral therapy.

"This sets the stage to start teasing apart the relative contributions of different causes for immune activation in people with HIV," said Mark Wallet, Ph.D., an immunologist and postdoctoral researcher who is first author of two of the papers. "We can eventually use that information to better treat HIV-infected individuals by targeting the inflammation that causes so many long-term illnesses."

The researchers turned to rheumatoid arthritis to study the role of another molecule called interferon gamma. Produced in inflamed joints, it sets off an immune system process that is completed by a compound found in the natural lubrication fluid of joints. That compound has been shown to inhibit inflammation.

But it might also promote inflammation, the UF team has now shown. They found that in the presence of interferon gamma, the compound acted on macrophages to elevate production of two inflammation-causing proteins and suppress a protein that usually regulates normal immune cell responses.

"We're striving to dissect the initiating events that lead to chronic inflammation," Wallet said. "Immune cell activation and inflammation can become self-sustaining processes that are difficult to silence once a disease has progressed too far."

The researchers learned more about the roles of LPS and interferon gamma through a technique called proteomics, which gives a wealth of information that allows researchers to pinpoint specific changes within cells. It is a major shift from previous methods that rely on measuring secretions or biomarkers produced as a result of unspecified changes in cells.

"It's kind of like molecular archeology. We're getting pieces of a puzzle and trying to reconnect things in a biological context to infer what caused these events and get a better idea of what to focus on for future studies," said Joseph Brown, Ph.D., first author of one of the papers, who now works at Pacific Northwest National Laboratory in Richland, Wash. "What we're trying to do is better understand why the immune system is so off course, so exaggerated."

The work brings to light variations in protein expression patterns that relate to macrophage activation gone awry.

"This type of work is really critical to identifying specific fingerprints -- target proteins that could be either enhanced or suppressed," said Luis Montaner, D.V.M., M.Sc., D. Phil., editor-in-chief of the Journal of Leukocyte Biology and a professor of immunology at The Wistar Institute, who was not involved in the studies. "Getting a clear definition of what that means in the protein expression site can give the ability to target those proteins rather than the whole sequence."

Story Source:

    The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Florida.

How To Fortify The Immunity Of HIV Patients

January 04, 2011

New findings from a Université de Montréal and the Vaccine and Gene Therapy Institute of Florida (VGTI) study, in collaboration with scientists from the NIH and the McGill University Hospital Center, may soon lead to an expansion of the drug arsenal used to fight HIV. The Canada-U.S. study published today in the journal Nature Medicine characterizes the pivotal role of two molecules, PD-1 and IL-10, in influencing the function of CD4/T-helper cells and altering their ability to fight HIV.

"Our findings show that the membrane protein PD-1 is up-regulated during HIV infection by the release of bacterial products from the gut and this subsequently increases the production of a cell derived factor, IL-10 that paralyses the immune system ," says senior author Dr. Rafick-Pierre Sékaly, a professor at the Université de Montréal, researcher at the Centre de Recherche du CHUM and scientific director of the Vaccine and Gene Therapy Institute of Florida. "We are the first to show that these two molecules work together to shut down the function of CD4 T-cells in HIV patients. This in turn, may lead to paralysis of the immune system and an accelerated disease progression ."

"Our results suggest that it is important to block both IL-10 and PD-1 interactions to restore the immune response during HIV infection," says Dr. Sékaly. "We believe that immunotherapies that target PD-1 and IL-10 should be part of the arsenal used to restore immune function in HIV-infected subjects."

About HIV treatment

During the last 20 years, treatment of HIV/AIDS has evolved and now uses highly active anti-retroviral therapy (HAART) that involves at least three active anti-retroviral medications. The HAART "cocktail" is a potent suppressor of viral replication in the blood. Although, HAART has been shown to delay the progression of AIDS and prolong life, it is not curative. The quest for improved treatments continues.

Partners in research

This study was funded by the Canadian Institutes of Health Research, the Canadian Foundation for Infectious Diseases, the Fonds de la recherche en santé du Québec, the National Institutes of Health, the Canadian Foundation for AIDS Research and the Canadian Network for Vaccines and Immunotherapeutics.

"PD-1 Induced IL-10 Production by Monocytes Impairs CD4 T-Cell Activation during HIV Infection,"
Elias A. Said, Franck P. Dupuy, Lydie Trautmann, Yuwei Zhang, Yu Shi, Mohamed El-Far, Brenna J. Hill, Alessandra Noto, Petronela Ancuta, Yoav Peretz, Simone G. Fonseca, Julien Van Grevenynghe, Mohamed R. Boulassel, Julie Bruneau, Naglaa H. Shoukry, Jean-Pierre Routy, Daniel C. Douek, Elias K. Haddad, Rafick P. Sekaly.

Université de Montréal

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