News (Updated May 16, 2010)

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Novel Pouch Could Reduce Mother-to-Infant HIV Infection

May 16, 2010

DURHAM , N.C. -- By using medications packaged just like fast-food ketchup, HIV-positive mothers in developing countries can more easily provide protection to newborn babies born at home.

Biomedical engineers at Duke University have developed an inexpensive and easy-to-use system that allows mothers to give their newborns a potentially life-saving dose of an anti-HIV medication shortly after birth. This is especially important since such drugs can only be found in clinics or hospitals, which can be days away from an expectant mother.

Timing is crucial for the newborn.

In order to be effective, the drug, known as Nevirapine, must be given to the newborn within days of birth. The challenge to date has been reaching distant mothers who give birth at home. Since most mothers are not up to traveling that soon after delivery to get medication, the biomedical engineers developed a way of providing the medication in a simple manner and with a long shelf-life --- pouches made of foil and plastic that can hold a single dose of Nevirapine.

“In Africa , the World Health Organization (WHO) estimates that more than 90 percent of 430,000 new cases of AIDS in 2008 were attributable to mother-to-child transmission,” said Carolina Gamache, program coordinator in senior researcher Robert Malkin’s Developing World Healthcare Technology Laboratory at Duke’s Pratt School of Engineering. “A single dose of Nevirapine right after birth has been shown to be effective in protecting the baby from the virus, but it has been difficult for many reasons to make this option available to women who give birth at home.”

Gamache presented the results of the Duke research in London at the Appropriate Healthcare Technologies for Developing Countries conference, which is sponsored by WHO and the Institute of Engineering and Technology. Her paper describing the team’s results was selected by judges as the conference’s top research paper.

While healthcare workers in Africa have in the past tried packaging single doses by other means – syringes and containers – they have all suffered from evaporation during storage and loss of preservatives. This is not an issue for bulk quantities of the drug, which are common in clinic and hospital pharmacies.

Also, as Gamache explained, drug manufacturers have not shown much interest in devising single-dose systems because of development costs and limited marketing potential outside the Third World . The new pouch, which was fabricated at Duke, has been shown in tests to greatly reduce evaporation while remaining potent at various temperatures – all greatly extending its life span.

“In our system, the pharmacist can fill an individual pouch for women early in their pregnancy, and they can take it home with them,” Gamache said. “When the baby is born, the mother can then easily rip off the corner of the pouch and empty the drug into the newborn’s mouth. Further treatments can be given to the baby at the clinic or hospital later when travel becomes easier for the mother.”

The WHO estimates that just 32 percent of infants born to HIV-positive mothers received prophylactic antiretroviral drugs like Nevirapine, compared to 45 percent of their pregnant mothers.

“If borne out in upcoming clinical trials, it would be expected that the current gap in anti-retroviral prophylaxis between mothers and their children could be reduced with the pouch,” Malkin said. “This could be accomplished at little additional cost and could be a significant step in creating a generation of children free of HIV.”

The team has conducted field testing the past year on the use of the pouches with nurses and pharmacists in Tanzania , and based on the encouraging results, they are planning clinical trials to determine if the new system can reduce the number of mother-to-child cases of HIV transmission.

Although the latest studies were conducted with Nevirapine, the Duke researchers also plan to test the system with other anti-HIV medications and combinations of medications.

The research was supported by Duke’s Research in Practice Program and the Provost’s Common Fund. Pratt undergraduates Michael Spohn, Shannon Skinner and Peter Horgan were also part of the team.

 

Genital wart virus may raise men's risk of HIV

May 10, 2010

NEW YORK (Reuters Health) - Men who carry the virus that causes genital warts may be at increased risk of HIV infection, a study of Kenyan men suggests.

Health

Researchers say the findings raise the possibility that vaccination against the virus, known as the human papillomavirus (HPV), could help curb the world's HIV pandemic.

The investigators found that among 2,168 Kenyan men between the ages of 18 and 24, half tested positive for HPV at the start of the study. Over the next 3.5 years, nearly 6 percent of those men became infected with HIV, versus just under 4 percent of those who had tested HPV-negative at the outset.

When the researchers controlled for a number of HIV risk factors, men with HPV were still 80 percent more likely than their HPV-negative counterparts to become infected with HIV, suggesting the genital wart virus itself may boost a person's susceptibility to HIV.

The findings are published in the Journal of Infectious Diseases.

There are more than 100 strains of HPV, some of which cause genital and anal warts. In most people, the immune system clears the infection fairly rapidly. However, persistent infection with certain HPV strains can eventually lead to cancer in some cases.

Persistent HPV infection is the primary cause of cervical cancer, and it can also lead to cancers of anus and penis.

The current findings come from a larger clinical trial that, along with two other trials in Africa in 2005 and 2006, found that circumcision lowered men's risk of acquiring HIV through heterosexual sex. Subsequent studies of those men have shown that circumcision may also lower the odds of HPV infection.

In this latest study, HPV infection itself was linked to a higher risk of acquiring HIV even when the researchers factored in circumcision, as well as the men's reported sexual history and whether they had the genital herpes virus -- which has already been linked to an increased risk of HIV infection.

All of this suggests that HPV vaccination, along with circumcision, could help stem the HIV pandemic, according to lead researcher Dr. Jennifer S. Smith, of the University of North Carolina at Chapel Hill .

"Finding a vaccine to prevent HIV is the greatest hope for curbing the world's AIDS pandemic, but so far there is no such vaccine," Smith said in a written statement from the university. "However, there is a vaccine to prevent specific types of HPV infection, and vaccinating young men before they become sexually active could potentially help prevent the spread of HIV."

There are two vaccines that can prevent infection with certain cancer-related strains of HPV: Gardasil (from Merck) and Ceravix (from GlaxoSmithKline). In the U.S. , the vaccines are approved for girls and young women as young as 9, and up to the age of 26. Last year, regulators approved Gardasil for boys and men in the same age group.

The current findings, according to Smith's team, warrant clinic trials to test whether HPV vaccination can lower the risk of HIV infection.

If vaccination does prove effective, cost could stand as a major obstacle to bringing it to developing nations where HIV transmission rates are high. The required three doses of the HPV vaccines cost roughly $400 in the U.S.

It's not clear why HPV infection might increase the odds of HIV infection, but it is biologically plausible, according to Smith's team. Skin lesions caused by HPV, for example, might act as "portals of HIV entry," the researchers note. In addition, HPV may induce the production of certain inflammatory proteins in the genital area, which may in turn boost susceptibility to HIV infection.

The study was funded by the U.S. National Institutes of Health and the Canadian Institutes of Health Research.

SOURCE: Journal of Infectious Diseases, June 1, 2010.

 

Primary Care Docs Handling More HIV Cases

Over half of those surveyed have patients who have tested positive for the disease

FRIDAY, May 14 (HealthDay News) -- A new U.S. survey, touted as the first of its kind, reveals that primary care doctors are taking over a larger share of care for people with HIV, the virus that causes AIDS.

Fifty-four percent of primary care doctors surveyed said they treat HIV-positive patients, and 43 percent said the number of HIV cases they treat had increased over the past year.

Among primary care physicians who treat HIV-positive patients, more than one-third said they see more than 200 cases a year.

"The state of HIV primary care is evolving rapidly, with serious implications for the health-care system," Brian Hujdich, executive director of HealthHIV, the organization that commissioned the report, said in a news release.

Hujdich called on more medical education for primary care doctors so they can provide better care.

HealthHIV, located in Washington , D.C. , is a non-profit organization that provides education, technical assistance and health services research to organizations, communities and professionals to advance the care and support for people living with, or at risk for, HIV/AIDS.

The report, based on a national survey of 1,165 respondents, will be presented in July at the International AIDS Conference in Vienna .

 

NIH Grant To Advance Companion Diagnostic Tests For Identifying Antiviral Toxicity

16 May 2010   

MitoSciences announces that it has just been awarded $590,000 by the National Institutes of Health to support the development of companion diagnostic tests for antiviral drugs. The award was made after competitive scientific review and was issued under The American Recovery and Reinvestment Act of 2009.

The tests, developed in collaboration with the University of Oregon , allow clinicians to identify adverse effects from drugs used to treat HIV/AIDS, hepatitis, and other infectious diseases. Many of these drugs are known to cause toxic side effects, often due to inhibition of mitochondrial function. Mitochondria are the powerhouses of the cell and produce most of the energy needed to keep us alive. Given this critical role, drug-induced inhibition of mitochondrial function can cause a variety of serious physiological conditions. MitoSciences has demonstrated that its tests can identify drug toxicity early, often before outward signs of the conditions can be observed clinically.

The problem of mitochondrial toxicity is now sufficiently well-recognized that the FDA recently released recommendations that all new antiviral drug candidates should be screened for toxicity to mitochondria. MitoSciences' tests have been used by multiple antiviral drug developers in their FDA submissions.

"Drug-induced mitochondrial toxicity is a problem that is receiving growing recognition," said Jean-Paul Audette, CEO of MitoSciences. "A number of drugs that were removed from the market are now known to inhibit mitochondrial function, and we are working with groups at most of the world's largest drug companies to help them include mitochondrial toxicity screening earlier in their safety assessment programs."

MitoSciences has developed the MitoTox™ line of assays, which is the most complete set of solutions for identifying adverse mitochondrial effects caused by a wide range of therapeutic compounds. The MitoTox™ line of assays is offered both as kits and also as a service through MitoSciences' CRO division. MitoSciences is also working to validate several of the MitoTox™ assays for use in clinical applications, such as companion diagnostics, and in this effort is collaborating with leading clinical researchers in multiple countries.

Source
MitoSciences

 

IAVI Statement For World AIDS Vaccine Day

16 May 2010   

In the 27 years since HIV was discovered, scientists have learned a great deal about the virus and how it causes AIDS. Making a vaccine to stop it, however, has proved a greater challenge than anyone could have imagined. Plain good news in this field has been a rarity. So it is with special pleasure that we note on this World AIDS Vaccine Day, May 18, that there has been a sizeable dose of it in the past year.

Last September, a candidate vaccine regimen tested in a large clinical trial in Thailand protected volunteers from HIV with 30% efficacy. That's not as protective as we'd like a vaccine to be. Still, the result electrified the field: it was the first demonstration in humans that an AIDS vaccine is possible. The challenge now is to build better AIDS vaccines.

Weeks prior to the release of those results, researchers at and affiliated with the International AIDS Vaccine Initiative (IAVI) served up another advance: the discovery of two powerful new antibodies capable of neutralizing a wide variety of HIV variants and the identification of the site on the virus to which they attach. This site provides researchers with a promising new model to use to design a vaccine against AIDS. Subsequently, researchers affiliated with IAVI and the U.S. National Institutes of Health have discovered still more broadly neutralizing antibodies to HIV.

Of course, making a vaccine against HIV remains one of the toughest problems of modern science.

The considerable work that lies ahead will include, first, the continued clinical assessment of candidate AIDS vaccines. That the protective effect seen in the Thai trial was a surprise to most researchers was instructive, underscoring the vital importance of human testing. It is especially important that researchers devise and test candidate HIV vaccines that are of relevance to the developing world, particularly sub-Saharan Africa , where the overwhelming majority of new HIV infections occur. It is thus necessary to build and sustain sufficient human and infrastructure capacity to conduct the required research in such places. Part of that effort will be the cultivation of international collaborations that engage the best researchers, companies, clinical research centers and technologies from around the world.

Second, we believe, HIV researchers must harness the latest scientific insights and technological tools to generate potentially more promising HIV vaccine candidates for human trials. These would include candidates designed to induce immunity in the lining of the gut, where HIV replicates early in the course of infection. It would include candidates that, though safe, behave more like naturally occurring viruses and are meant to elicit more vigorous immune responses. Perhaps most important, it would include candidates that prompt the immune system to deploy powerful antibodies like the ones recently discovered, which neutralize the majority of HIV variants circulating in the world.

"With 7,400 people newly infected with HIV every day, the best hope we have of ending this human catastrophe is to develop and widely distribute effective vaccines against the virus," said Seth Berkley, the CEO and founder of IAVI.

Success in that endeavor will depend on the continued support of policymakers, advocates, community representatives, researchers, nongovernmental organizations, commercial enterprises, donors and, not least, the volunteers who participate in vaccine and related studies, seeking nothing in return for their trouble but the satisfaction of doing their bit to rid the world of AIDS. On this thirteenth World AIDS Vaccine Day, we at IAVI extend our heartfelt thanks to all of these parties for their dauntless determination and tireless efforts to make AIDS vaccines a reality.

Source
International AIDS Vaccine Initiative (IAVI)

 

Liver deaths on rise due to 30-year-old hep C epidemic

Study of sufferers finds mortality could double in Lothians

15 May 2010

By ADAM MORRIS

HEALTH chiefs have been warned to prepare for a huge rise in liver deaths linked to a hepatitis C epidemic 30 years ago.

A report studying the health of sufferers over 15 years has found that the number dying from liver disease could double across the Lothians.

It has caused a shock not only for the estimated 6,000 living with the illness in the Lothians, but also for NHS bosses who may have to cope with the hike.

The paper – released by the Eurosurveillance journal and the first of its type – also warned that Scotland 's higher than normal alcohol problem has masked the threat of hepatitis C to the population's liver health.

People who caught the disease in the 1970s and 1980s are now entering their third and fourth decade living with the illness, and it has prompted calls for more testing of the disease.

It is estimated that half the people who have been infected don't know it. Given that it is curable in around 50 per cent of cases, it is those living in ignorance who are in most danger.

The report warned: "Over the past 15 years we have observed an increasing contribution from hepatitis C infection to mortality due to liver-related causes in Scotland .

"Deaths increased steadily among the 35-54 years age group, and the largest percentage of deaths linked to the hepatitis C diagnosis database were of people born from 1950 to 1959.

"This is consistent with infection of young people in the 1970s and 1980s – before hepatitis C was identified – and the natural history of chronic hepatitis C."

The illness has caught up with thousands of Edinburgh adults, some of whom only dabbled in drug use and discovered they were infected sometimes two decades later. It is thought that in Scotland around 100 people a year die from liver disease linked to hepatitis C, a figure set to soar.

The problem has become so noticeable that the Hepatitis C Trust – traditionally an English-based charity – opened an office in Scotland at the end of last year. A spokeswoman for the organisation said: "For people in their 50s perhaps too scared or embarrassed to get tested, it is something they really have to do, because the next step can be liver disease and death.

"It's actually just as cost effective for the NHS to treat someone now than to wait until they need treated for liver disease. People at risk only need to have injected once, or even just have had a dodgy tattoo."

Scottish agencies Health Protection Scotland and ISD Scotland were also involved in producing the publication.

The report continued: "Hepatitis C infection constitutes a significant, growing, public health burden in Scotland in terms of mortality from liver disease.

"A better understanding of the risk factors associated with developing hepatitis C-related liver disease will improve treatment and survival."

'Stupid mistake' that cost Petra

PETRA Wright "dabbled" briefly in drugs as a teenager, but decades later it caught up with her.

The 56-year-old was diagnosed with hepatitis C 25 years after the "stupid" mistake, and had long since turned her life around. Now having battled the disease for years, she is set to embark on a course of treatment this summer to finally rid herself of the condition.

When diagnosed she had to change her diet and give up alcohol, and even went to work for the Hepatitis C Trust, where she is now the charity's Scottish officer. She said: "Treatment is changing all the time and they're getting really quite smart at it.

"There is no reason for people not to get tested if they suspect they might have it.

"The symptoms are such that it's not always obvious, but new tests coming in can give you the result in 20 minutes.

"There's no need for it to be a death sentence.

"I think some people maybe assume it's something you have to manage – like HIV – rather than can simply cure."

 

Unique Nanomedicine Formulation For DermaVir Therapeutic Vaccine For HIV/AIDS

14 May 2010   

Genetic Immunity, a multi-national biopharmaceutical company developing nanomedicine vaccines announces publication of the Company's innovative work to develop a stable liquid formulation to deliver a novel nanomedicine. Appearing in the International Journal of Pharmaceutics, the paper addresses how Genetic Immunity was able to overcome significant hurdles facing the field to successfully formulate the first topically administered nanomedicine therapeutic vaccine for the treatment of HIV/AIDS, DermaVir.

"Biological activity of DermaVir depends upon its nanomedicine formulation that is essential for the potent expression of plasmid-DNA-encoded antigens. During Phase I and II clinical trials, DermaVir formulation required on-site admixture of three separate components followed by patient administration within three hours. We report here the development of a stable single liquid nanomedicine formulation, a significant milestone in developing DermaVir as a commercially viable global product to treat HIV/AIDS," commented Julianna Lisziewicz, PhD and CEO of Genetic Immunity.

Engineering novel nanomedicines presented Genetic Immunity with challenges not faced in the development of traditional biotechnology products. "One challenge in clinical nanomedicine development is to produce a stable formulation with reproducible manufacturing methods," explained Genetic Immunity's Enikö Töke, PhD. "We found several additional quality requirements of the components that were essential both to establish the optimal relationship between physicochemical properties and biological activity of DermaVir and to ensure reproducible manufacturing of a stable formulation. It became apparent that the current state-of-the-art approaches to sourcing, testing and manufacturing were insufficient."

Genetic Immunity implemented "Quality-by-Design" in biologic product development to manufacture a nanomedicine resulting in a new formulation of pDNA surrounded by a chemical polymer capable of maintaining the physical stability and biological activity of DermaVir at 4ºC.

These discoveries will support DermaVir as it enters into Phase II/III human trials as a topically administered nanomedicine therapeutic vaccine. "Our Phase I trial demonstrated the preliminary safety and immunogenicity of DermaVir in HIV-positive people treated with HAART," Lisziewicz explained. "We have now also obtained Phase II data showing safety, immunogenicity and viral load reductions when DermaVir is used for initial treatment of HIV-infected individuals. This is the human proof of concept of our topical nanomedicine vaccine technology. It is our belief that DermaVir will become the first nanomedicine vaccine developed to reconstitute HIV-specific immunity with the potential to maintain the health of people living with HIV infection."

Source
Genetic Immunity

 

Link Between Frequent Alcohol Use And Faster HIV Disease Progression

14 May 2010   

HIV disease tends to progress at a faster rate in infected individuals who consume two or more alcoholic drinks a day, according to an important new paper in AIDS Research and Human Retroviruses, a peer-reviewed journal published by Mary Ann Liebert, Inc. The article is available free online.

The article, entitled "Alcohol Use Accelerates HIV Disease Progression," clearly demonstrates that frequent alcohol use, defined as two or more drinks daily, is associated with declining CD4+ cell counts (which indicate a weakened immune system) in individuals with HIV disease who either are or are not receiving antiretroviral therapy (ART). Based on the results of a 30-month prospective study, the authors, Marianna Baum, Carlin Rafie, Sabrina Sales, and Adriana Campa, from Florida International University (Miami), Shenghan Lai, from Johns Hopkins University, and John Bryan Page, from University of Miami, Florida, conclude that alcohol has a direct effect on CD4 cells and that the accelerated decline in CD4+ cell counts in frequent alcohol users is not simply due to poorer adherence to ART in this population.

Another article by Natascha Ching, Karin Nielsen-Saines, Jaime Deville, Lian Wei, Eileen Garratty, and Yvonne Bryson, from the David Geffen School of Medicine at UCLA, Los Angeles, CA, demonstrated that children who were infected with HIV while in utero via maternal-fetal transmission, were subsequently given antiretroviral therapy, and had no detectable HIV in their blood, still produced neutralizing antibodies against HIV, suggesting that low levels of viral replication might still be occurring despite drug therapy. In the article "Autologous Neutralizing Antibody to Human Immunodeficiency Virus-1 and Replication-Competent Virus Recovered from CD4+ T-Cell Reservoirs in Pediatric HIV-1-Infected Patients on HAART," the authors present data to support their conclusion that the children's CD4 T-cells may contain latent HIV reservoirs that formed early in life before antiretroviral therapy was initiated.

"It is important that HIV infected individuals make informed decisions relating to alcohol consumption. This article will help to achieve that goal," says Thomas Hope, PhD, Editor-in-Chief of AIDS Research and Human Retroviruses and Professor of Cell and Molecular Biology at the Feinberg School of Medicine, Northwestern University , Chicago , IL .

Source:
Vicki Cohn
Mary Ann Liebert, Inc./Genetic Engineering News


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