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.
Tido von Schoen-Anderer, head of Medecins Sans Frontieres' Campaign for Access to Essential Medicines, said, "These new guidelines are good news." He added, "Before there were so many different drug options and now there is much clearer guidance, and that has major advantages at the program level, and also the choice of drugs means it's going to be cheaper." Andy Gray, a consultant pharmacist for the Centre for the AIDS Programme of Research in South Africa, said he welcomes the guidelines but worries that the choices might be too restrictive. "Limiting the number of second-line options may look attractive to a country program, but in a middle-income country such as South Africa, there's going to be a lot of pressure from clinicians that they need more options," Gray said. Von Schoen-Anderer added that "in terms of making second-line treatment more available, the only way forward was to make it simpler and easier to implement" (PlusNews, 2/7).
Link to this story.
Global Challenges
Violence in Kenya Reducing Access to Antiretrovirals Among People Living With HIV/AIDS
[Feb 11, 2008]
Thousands of people living with HIV/AIDS in Kenya have been forced to discontinue their antiretroviral treatment as a result of ongoing political violence throughout the country, the World AIDS Campaign said recently, Inter Press Service reports. About 21,000 people living with the disease have been displaced from their homes since the violence began in December 2007, according to the Kenya-based advocacy group United Civil Society Coalition for AIDS, TB and Malaria.
Many people have not had access to clinics because of the violence or forced relocation, according to the World AIDS Campaign. Some people left their homes without the medical records required to access treatment, while others' documents were lost when their houses were burned. Discontinuing treatment could have severe health implications at an individual level, and it also could lead to an increase in the number of new cases within refugee camps, advocates have said. In addition, HIV/AIDS-related stigma has made some people reluctant to seek available treatment because of fears that they will be ostracized, Allan Ragi, the executive director of the Kenya AIDS NGOs Consortium, said.
"Kenya was making some very real progress in terms of reducing the prevalence rate and bringing their rates of infection down," Stephen Lewis -- former United Nations special envoy for HIV/AIDS in Africa who now directs the group AIDS-Free World -- said, adding, "This is a terrible setback in human terms." Lewis called on the United Nations to provide emergency medical assistance, such as discreet medical shelters within refugee camps that provide HIV/AIDS services. The World Health Organization reported last week that workers in Eldoret, Nakuru and Naivasha -- three towns in Kenya's Rift Valley Province -- were coordinating medical activities in camps and hospitals to evaluate the health conditions. Teams in several other areas have been unable to report for duty for security reasons, according to Inter Press Service.
Some advocates say one solution would be for the United Nations to assist Kenya's HIV/AIDS grassroots organizations, which already have access and relationships with affected populations. KANCO has been collaborating with groups like the National Empowerment Network of People Living with HIV/AIDS in Kenya and the Kenya Network of Women Living with AIDS. Critical next steps for these groups include assessing the health system, operating health centers, drafting press releases and identifying new ways to expand the scope of counseling, Elizabeth Akinyi Osewe, a Kenya program officer for the International Community of Women Living with HIV/AIDS, said (Pollock, Inter Press Service, 2/8).
NPR's "All Things Considered" on Sunday included a discussion with Filipe Ribeiro, a medical coordinator for Doctors Without Borders, about how the violence in Kenya is affecting access to medical care (Seabrook, "All Things Considered," NPR, 2/10). Audio of the segment is available online.
Link to this story.
Australia To Provide Indonesia With $40M Million To Fight HIV/AIDS
[Feb 11, 2008]
Australia will allocate $40 million in 2008 to help fight the spread of HIV/AIDS in Indonesia, Australian Foreign Minister Stephen Smith announced on Thursday, the AAP/Australian reports. "I am pleased to announce today that in 2008, Australia will commence a new program with Indonesia to give people with HIV, or at risk of contracting HIV, better access to essential treatment and prevention," Smith said. Smith made the announcement after meeting with Indonesian Foreign Minister Hassan Wirajuda in Perth, Australia (AAP/Australian, 2/7).
The funding will go toward an HIV/AIDS program that aims to increase access to medicines and treatment among marginalized groups living with HIV/AIDS, AHN Media reports. According to the Indonesian Ministry of Health, the HIV situation in Indonesia is one of the fastest spreading in Asia. About 170,000 people are living with HIV/AIDS out of the country's 231.6 million residents. About 29,000 of those living with the disease are women. Most HIV cases occur among injection drugs users and commercial sex workers, followed by men who have sex with men, AHN Media reports. A 2005 survey found that 40% of IDUs in Jakarta tested positive for HIV. The survey also found that about 25% of IDUs in Bandung, Jakarta and Medan said they had had unprotected sex during the past year (Morales, AHN Media, 2/7).
U.N. Envoy Calls for Increased Efforts on HIV/AIDS in Indonesia
In related news, Nafis Sadik, United Nations Special Envoy for HIV/AIDS in Asia and the Pacific, on Friday called on Indonesia to scale up its HIV/AIDS prevention efforts while rates of the disease are still low among the general population, Reuters reports. "The window of opportunity is now open to keep the epidemic at low levels," Sadik said during a five-day visit to the country. "I am happy with the progress, but Indonesia needs to do more," Sadik said, adding, "Prevention has to be equal priority if not more priority in the program. Unless you prevent it, you are not going to get rid of HIV." Indonesia's National AIDS Commission estimates that the country will have one million cases by 2015 if efforts are not strengthened. Sadik said the country should bolster its existing programs to promote behavior change and condom use. However, religious groups have strongly criticized the campaigns, saying they promote promiscuity, according to the commission (Reuters, 2/8).
Link to this story.
Drug-Resistant TB Outbreaks in Africa, Ukraine Not Diminishing, Scientists Say
[Feb 11, 2008]
Outbreaks of drug-resistant tuberculosis in Africa and Eastern Europe that are often complicated by HIV/AIDS show no signs of slowing, researchers reported last week at the 15th Conference on Retroviruses and Opportunistic Infections in Boston, Reuters Health reports. Two teams of scientists presented studies at the conference about outbreaks of drug-resistant TB among HIV-positive people in South Africa and Ukraine.
South Africa Study
Neel Gandhi of the Albert Einstein College of Medicine and colleagues examined an outbreak of extensively drug-resistant TB -- which is resistant to the two most potent first-line treatments and some of the available second-line drugs -- and multi-drug resistant TB among HIV-positive people in South Africa's KwaZulu-Natal province. According to Gandhi, people who are HIV-positive people are "canaries in the mines" because they are among the first to exhibit symptoms of MDR-TB.
Between 2005 and 2006, Gandhi and colleagues evaluated 17 people with HIV/TB coinfection who began to show signs of drug-resistant TB. They observed that those with HIV/TB coinfection would develop drug-resistant TB soon after receiving successful treatment for drug-sensitive TB. The source of reinfection often was a new strain rather than a mutation from the original strain, the researchers found. Fifteen of the 17 people in the study died within weeks of being diagnosed with drug-resistant TB. Gandhi said the findings highlight the need for infection control to curb outbreaks.
Ukraine Study
In the second report, Matteo Zignol of the World Health Organization's project office in Donetsk, Ukraine, and colleagues evaluated all new and previous TB cases over a one-year period in the country. The team examined about 1,500 cases of TB, two-thirds of which were new and one-third of which occurred among people who had received previous TB treatment. Twenty-one percent of people also were living with HIV. The researchers found that 15.5% of the new TB cases were MDR-TB, one of the highest rates reported in a population study, Reuters Health reports.
The team also found that HIV was a reliable indicator of MDR-TB. Death rates from TB also were significantly higher among HIV-positive people. Separate risk factors included a history of incarceration and previous TB treatment, the findings showed. According to Zignol, the study's most important implication is the need to improve preventive procedures, especially in prisons and hospitals. Zignol said the study will be submitted to the Ukrainian government with recommendations for changes in public health policy. He added that he is "quite optimistic" the government will consider the recommendations (Mitchell, Reuters Health, 2/7).
Link to this story.
Opinion
'Conscious Effort' Should Be Made To 'Enhance' Health Infrastructure Benefits Provided by Disease-Specific Programs, Opinion Piece Says
[Feb 11, 2008]
"Governments of the world's richest nations have launched significant responses to the rampant health crises of those living in the poorest nations," Boston Globe columnist James Carroll writes in an opinion piece. He adds that "wealthy individuals, like Bill and Melinda Gates, are also making extraordinary interventions" and that President Bush's "request for a reauthorization of the President's Emergency Plan for AIDS Relief solidifies what will likely be regarded as the Bush administration's finest act."
However, global health and development issues are so complex that "even these proposals spark controversy," Carroll writes, adding that some advocates say that the "entire 'disease-specific' approach ... is equally misguided." According to these advocates, "donors should be shoring up health infrastructures, not targeting particular diseases," Carroll says. "What the past five years" of PEPFAR illustrate, however, is that "disease-specific strategies do create systemwide collateral benefits, making the dichotomy false," Carroll writes, adding, "The point is now for planners and politicians to make a conscious effort to enhance that pattern." According to Carroll, opportunities "must be seized to expand in-country work forces of health professionals." He adds that the "focus on particular prevention programs must simultaneously broaden to encourage in ordinary people the fuller health consciousness on which systems depend."
The "demands of multiple health crises must not be reduced to a zero-sum game, with care for malaria or preparation for Avian flu set against the needs of those" living with HIV/AIDS, Carroll writes, adding, "By doubling the American dollar commitment to" the disease in Africa, Bush "gave an example of what is needed -- which is a drastic expansion of financial support for the health of people living in poorer nations." Expanding the global "response to this disease can prompt a needed expansion of our responses to the others," Carroll writes, concluding, "And responding with focus to each disease can help the broader health systems of the world become what they must be" (Carroll, Boston Globe, 2/11).
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