Kaisernetwork.org (Washington, DC)
11 February 2008
Science & Medicine
Molecule That Directs Immune Cells to Intestines Also Serves as Receptor for HIV, Study Finds
Researchers Develop Technique That Prevents HIV From Reproducing, Philadelphia Inquirer Reports
Drug Access
WHO Releases New Guidelines on Second-Line Antiretrovirals
Global Challenges
Violence in Kenya Reducing Access to Antiretrovirals Among People Living With HIV/AIDS
Australia To Provide Indonesia With $40M Million To Fight HIV/AIDS
Drug-Resistant TB Outbreaks in Africa, Ukraine Not Diminishing, Scientists Say
Opinion
'Conscious Effort' Should Be Made To 'Enhance' Health Infrastructure Benefits Provided by Disease-Specific Programs, Opinion Piece Says
Science & Medicine
Molecule That Directs Immune Cells to Intestines Also Serves as Receptor for HIV, Study Finds
[Feb 11, 2008]
A molecule called integrin alpha-4 beta-7 that naturally directs immune cells to the intestines also serves as a receptor for HIV, according to a study conducted by NIH's National Institute of Allergy and Infectious Diseases and published Sunday in the journal Nature Immunology, the New York Times reports. The study's findings have identified a new human receptor for the virus, according to the Times.
HIV rapidly infects the lymph nodes and lymph tissue found in the intestines, which become the primary location where the virus replicates, the Times reports. After HIV replicates in the intestines, the virus depletes the lymph tissue of CD4+ T cells. This situation occurs in all HIV-positive people regardless of the mode of transmission, the Times reports.
For the study, NIAID director Anthony Fauci and colleagues showed that a protein on the outer shell of HIV attaches itself to a molecule in the receptor that is linked to the way T cells find the digestive tract. The study also found that the binding of HIV to the molecule stimulates activation of another molecule, LFA-1, which helps spread the virus from one cell to another. These actions ultimately lead to the destruction of lymph tissue, according to the Times.
Fauci in an interview said the study "took nearly two years, and there's little doubt that what we have found is a new receptor" (Altman, New York Times, 2/11). He added, "It is the very molecule that steers lymphocytes to the gut and keeps them there." According to Fauci, "It is not only important in that it is a homing receptor to the gut. But it also can play a role in enhancing the ability of HIV to spread in the body." Elena Martinelli, a researcher involved in the study, said, "The gut is where the virus really takes hold." She added, "We found that integrin alpha-4 beta-7, whose natural function is to direct T cells to the GALT, is also a receptor for HIV. It is very unlikely that this is a coincidence" (Fox, Reuters, 2/10).
Warner Greene -- director of the Gladstone Institute of Virology and Immunology who was not involved in the study -- said the findings are "an important advance in the field." He added, "They begin to shed light on the mysterious process on why the virus preferentially grows in the gut." Fauci said he hopes the results will encourage other scientists from different disciplines to explore new ways to attack HIV, adding that drugs aimed at blocking the molecule also should be studied for their potential benefit in HIV/AIDS treatment (New York Times, 2/11).
The study abstract is available online.
Link to this story.
Researchers Develop Technique That Prevents HIV From Reproducing, Philadelphia Inquirer Reports
[Feb 11, 2008]
Researchers from the biotechnology company Virxsys and the University of Pennsylvania have developed a gene therapy technique that prevents HIV from reproducing, according to a study presented Wednesday at the 15th Conference on Retroviruses and Opportunistic Infections in Boston, the Philadelphia Inquirer reports.
For the study, the researchers removed CD4+ T cells from an HIV-positive person and inserted the cells into a gene that stops the virus from reproducing. The researchers then used a University of Pennsylvania patented technology to multiply the T cells one hundred-fold and put them back into the patient using a harmless version of HIV. The gene into which the researchers inserted the T cells prevents HIV from containing itself in a shell, making the virus unable to reproduce and form new HIV-infected cells. The study also found that HIV self-destructed when the gene was inserted back into the patient.
The study examined nine randomly chosen HIV-positive people and found that all nine had high HIV viral loads after undergoing the treatment but that most of the virus had mutated into harmless forms. A clinical trial among 54 HIV-positive people is ongoing to determine the safety of the technique, called VRX496, and the best dosages. None of the trial participants has experienced serious negative side effects, and many have suppressed HIV viral loads and increased their T cells.
The technique "raises hope" within the HIV vaccine research community that if a preventive vaccine is not developed, the technique could be used to control HIV among people already living with the virus, the Inquirer reports. Gary McGarrity, executive vice president for scientific affairs at Virxsys, said the "buzzword" in gene therapy research is "viral 'fitness'" and that VRX496 "diminishe[s] HIV fitness up to two years after treatment."
The possibility of the technique becoming an FDA-approved treatment is several years away, but Virxsys CEO Riku Rautsola estimated the potential cost for a one-time series of infusions would be $130,000, compared with the roughly $700,000 cost for lifetime treatment with antiretroviral drugs. Rautsola said the company hopes the treatment will become a "frontline therapy," adding that it "would clearly be better in terms of quality of life" for people living with HIV/AIDS (McCullough, Philadelphia Inquirer, 2/7).
Link to this story.
Drug Access
WHO Releases New Guidelines on Second-Line Antiretrovirals
[Feb 11, 2008]
The World Health Organization recently released new guidelines on second-line antiretroviral drugs in an attempt to assist developing countries in formulating treatment policies, PlusNews reports. The guidelines aim to speed approval for second-line antiretrovirals and reduce costs. The guidelines also will reduce the number of second-line drugs with WHO approval, PlusNews reports.
According to PlusNews, many second-line antiretrovirals are prohibitively expensive or unavailable in developing countries, and physicians often lack knowledge about or experience with what combination to prescribe HIV-positive people. The guidelines -- created from meetings held in May 2007 -- in part were released in response to requests from governments for more direction on which second-line antiretrovirals to include in their countries' treatment programs, PlusNews reports. The guidelines also address other barriers to drug access, including the lack of capacity in many developing countries to administer tests that diagnose resistance to first-line drugs. The guidelines read, "In order to maximize the efficacy and durability of first- and second-line antiretroviral regimens, WHO continues to support the universal availability and use of appropriate and affordable [CD4+ T cell] and HIV viral load testing."
According to WHO estimates, of the two million HIV-positive people in low- and middle-income countries with treatment access as of December 2006, 2% were on second-line drugs. That number will increase because about 3% of people receiving first-line drugs switch to second-line drugs annually. WHO said that without price reductions, the cost of second-line drugs -- which can cost two to nine times more than first-line drugs -- could account for as much as 90% of funding used for antiretroviral treatment by 2012. According to the Clinton Foundation HIV/AIDS Initiative, the prices of various generic second-line drugs currently in the pipeline or awaiting regulatory approval will depend on limiting the number of different drugs used for second-line treatment.
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