HIV and sexual health charity Terrence Higgins Trust (THT) has announced it is to hold an HIV conference in Eastbourne on 1st December. This one day event is timed to coincide with World Aids Day. Today, THT is putting out a call for people living with HIV in East Sussex to get actively involved in the planning of the conference by joining the HIV Working Party. The conference aims to look at how current services in the region could be improved, so it’s crucial that the views of people who are directly affected are heard.

THT is working with East Sussex County Council to launch the conference, which will be the first of its kind in the region and will give people who are HIV positive, community groups and campaigners the opportunity to have their say about current HIV services in the region. In 2008, there were 445 new diagnoses of HIV and over 5,000 people living with HIV on the South East coast, while across the UK more people are living with the condition than ever before.

Daniel Murray, HIV Health Coach for Terrence Higgins Trust in Eastbourne said: “We’re really keen for people living with HIV to get on board. It’s vital that we hear first hand from local people about their views on local services. This is an opportunity to make sure that your voice is heard so If you’re interested do get in touch.”

Source
Terrence Higgins Trust

While studying an HIV protein that plays an essential role in AIDS progression, researchers at the University of Pittsburgh School of Medicine have discovered compounds that show promise as novel treatments for the disease.

HIV drug discovery efforts have met with little success in finding compounds that interact with an important HIV virulence factor, called Nef, because it lacks biochemical activity that can be directly measured, explained Thomas E. Smithgall, Ph.D., William S. McEllroy Professor and Chair, Department of Microbiology and Molecular Genetics, and senior author of the paper, which was published in the early, online version of ACS Chemical Biology.

To get around that problem, Dr. Smithgall’s team developed an assay to measure Nef function indirectly by coupling it to another protein, called Hck, which Nef activates in HIV-infected cells. Because Hck activity can be easily measured, the investigators were able to use it as a reporter for Nef activity in an automated high-throughput screening process. In collaboration with the University of Pittsburgh Drug Discovery Institute, they screened a library of 10,000 chemical compounds against the coupled proteins to see which ones influenced Nef-induced activation of Hck.

After further testing, they confirmed that three compounds inhibited the activity of the Nef-Hck complex and, more importantly, all of them also interfered with HIV replication. One compound was so effective that it suppressed HIV replication to undetectable levels in cell culture experiments.

“So we now have a way to rapidly and efficiently screen for inhibitors of Nef signaling through Hck,” Dr. Smithgall said. “But the surprise was that some of those inhibitors also showed strong antiviral activity in cell culture models.”

There is evidence that people infected with HIV variants that have mutations in the Nef gene take substantially longer to develop disease symptoms or AIDS, he said. In animal models, disrupting the production of Nef from the virus or its interaction with Hck also delays or prevents disease symptoms. The next challenge for the researchers will be to determine whether these compounds also interfere with progression of AIDS-like disease in animal models by blocking Nef function.

“Most current therapies for HIV infection use drugs that interfere with the function of viral enzymes such as reverse transcriptase or with the interaction of the virus and the host cell,” Dr. Smithgall said. “Targeting Nef represents an entirely new approach that could be useful to deal with issues such as drug-resistant HIV strains, and may slow the progression to AIDS.”

He added that Nef is just one of several so-called “accessory proteins” encoded by HIV which are important virulence factors in AIDS. Inhibitory compounds against some of the others might be revealed using a similar coupled protein approach for high throughput screening.

Co-authors of the paper include Lori Emert-Sedlak, Ph.D., Toshiaki Kodama, Ph.D., and Edwina C. Lerner, Ph.D., Department of Microbiology and Molecular Genetics, School of Medicine; Weixiang Dai, Ph.D., and Billy Day, Ph.D., Department of Pharmaceutical Sciences, School of Pharmacy; and John S. Lazo, Ph.D., Department of Pharmacology and Chemical Biology, School of Medicine. Drs. Day and Smithgall also are members of the Drug Discovery Institute, which is directed by Dr. Lazo.

The research was supported by grants from the National Institutes of Health.

Source:
Anita Srikameswaran

University of Pittsburgh Schools of the Health Sciences

By discovering the atomic structure of a key human enzyme, researchers at The University of Texas at Austin have pointed the way toward designing anti-HIV drugs with far less toxic side effects.

Their work was published this week in Cell.

“Many anti-HIV drugs are designed to stop the process of DNA replication,” says Dr. Whitney Yin, assistant professor of chemistry and biochemistry. “That turns out to be a great thing to do to help cure virus infections, because it stop the processes of viral replication.

“At the same time, however, when you target such a critical process in viruses, you may also target human enzymes that perform similar functions in normal cells, and this is what causes harmful drug side effects.”

Yin and her graduate student, Young-sam Lee, have solved the atomic structure of an enzyme, known as Pol ? (pol gamma), that is responsible for DNA replication in human mitochondria.

When mitochondria are working normally, they produce most of the energy that sustains human cells. When pol gamma comes into contact with certain anti-retroviral drugs, however, it can incorporate the drug into mitochondrial DNA, and thus interfere with the normal replication process. This interferes with the ability of mitochondria to function. The consequences can range from simple nausea to bone marrow depletion to organ failure.

“Patients who are taking this class of anti-HIV drugs have suffered these drug toxicities for a long time,” says Yin. “Dosages and combinations of drugs can be chosen so they don’t kill you, but they still can’t be used at their most effective concentrations against HIV. However, in large part because combination therapies have become more successful and patients are living longer, toxicity has become more of an issue than before.”

Although it’s been known for some time that pol gamma is responsible for mediating the toxicity of the drugs, Yin says, it has been difficult to design a drug that can distinguish between HIV and pol gamma without knowing the structure of pol gamma. With the structures of both pol gamma and HIV known, the differences between the two can be exploited in the design of new drugs that will be more selective (and thus less toxic) against HIV.

“This is a unique opportunity for drug design,” says Yin. “Now you have two pictures side by side. You have the viral target protein and the human protein. You know not to do anything in this region where the two proteins are similar, but rather focus in areas where they’re different.”

In addition to its relevance to anti-HIV drug design, Yin’s research is also helping to explain how mutations in pol gamma lead to various degenerative diseases, including epilepsy, encephalopathy and Alpers’ syndrome (a fatal childhood disease leading to brain and liver failure).

The National Institutes of Health (NIH) and the Welch Foundation funded the work.

Source:
Whitney Yin

University of Texas at Austin

ChemDiv, Inc. (ChemDiv) of San Diego has proudly announced that its wholly owned subsidiary Chemical Diversity Research Institute (CDRI ) of Moscow, Russia, has been chosen by Viriom Ltd. ( Viriom) of Moscow, Russia as a service partner in developing innovative HIV compounds. The program includes pre-clinical and clinical studies, which are expected to begin in 2010.

Viriom has recently signed the license agreement with Roche. Under the terms of this agreement Roche granted Viriom development and commercialization rights for potential novel HIV/AIDS medicine in Russia, Ukraine, Belarus and Kazakhstan. Subject to performance of the program Viriom will also receive license fees, development milestones and royalties on worldwide sales.

Vadim Bichko, Vice President Virology at ChemDiv, Inc., said: “We are excited about this new collaboration with Viriom and Roche. These novel HIV inhibitors have shown excellent antiviral properties in vitro, good bioavailability, PK and safety profiles, as well as a high genetic barrier to resistance. Based on pre-clinical studies to date, these molecules have the potential to become best in class HIV drugs.”

About VIRIOM

VIRIOM Ltd. is an innovative company that was established in 2009 to develop targeted medicines for HIV/AIDS. Basis is the Center of High Technologies ChemRar to which VIRIOM is affiliated. VIRIOM is planning to conduct research and clinical trials in Russia using the experience and knowledge of Russian scientists. Chemical Diversity Research Institute, Prudentas Ltd. and Drug Technologies Ltd.of ChemRar Hi Tech Center (ChemRar) as well as Moscow City Center for prevention and treatment of HIV/AIDS were selected as partners in this program.

About ChemDiv, Inc.

ChemDiv collaborates with pharmaceutical and biotech partners by enabling them to accelerate their R&D programs to higher value clinical inflection points. ChemDiv provides integrated drug discovery and early clinical development, extracting value from potential therapeutic candidates via rapid, streamlined outcomes and effective use of capital.

ChemDiv is the only vertically and horizontally integrated discovery and development CRO headquartered in San Diego, CA, with: unique access to the Eastern European emerging pharma market; rational drug design and medicinal chemistry in a broad range of therapeutic areas of target classes; world’s largest small molecule inventory; working with 20 top pharma and 100 top biotechs in all major markets.

With its successful 20 year business record in life sciences and over 500 research associates equivalent employed globally, ChemDiv has successfully prosecuted fully integrated programs from target to Proof of Concept (POC) and market registration.

About Chemical Diversity Research Institute.

CDRI is a contract research organization focused on pre-clinical and clinical R&D. CDRI sees its mission in enabling discovery and development of innovative therapies for unmet needs utilizing the highest expertise and innovation potential of Russian scientists with integrated external R&D solutions of Discovery outSource™ platforms. Discovery outSource™ platform solutions cover the complete range of disciplines from identification of a biological target (protein expression, assay development etc.); to clinical drug candidates (ADME/DMPK, toxicity and safety studies, in vivo animal models, drug formulation etc.); to drug development candidate (Phase I to Phase IV).

Source
ChemRar Hi Tech Center

An Austin, Texas orthopaedic surgeon has agreed that he and his staff will not deny or withhold medically appropriate treatment from patients solely because they are HIV-positive, according to the U.S. Department of Health and Human Services (HHS). Under a settlement agreement reached with HHS’ Office for Civil Rights (OCR), the surgeon, whose practice group sees an average of 200 patients per week, will establish a non-discrimination policy, make reasonable modifications to his procedures to avoid discrimination against individuals living with HIV/AIDS, receive comprehensive training, implement patient grievance procedures, and inform patients of their right to file a complaint with OCR.

The settlement agreement will bring the surgeon into compliance with Section 504 of the Rehabilitation Act of 1973 (Section 504). Section 504 requires recipients of federal financial assistance (often health care providers reimbursed by Medicaid) to ensure that qualified individuals with disabilities, including those with HIV/AIDS, have equal access to their programs, services or activities.

“Medical providers covered by Section 504 have a legal obligation to provide medically appropriate services to qualified individuals with disabilities,” said OCR Director Georgina Verdugo. “Under Section 504, medical providers may not deny or withhold medically appropriate treatment, as determined by reasonable medical judgment given the current state of medical knowledge, solely on the basis of a patient’s HIV status. As our investigation, violation finding, and settlement of this Austin case demonstrate, OCR is committed to ensuring that all qualified individuals with disabilities — including those with HIV/AIDS — are afforded equal access to quality medical services.”

The prevalence of HIV/AIDS in the greater Austin area has increased 63 percent since 2000 and is the third highest in the State of Texas, according to a Dec. 31, 2007, report of the Austin/Travis County Health and Human Services Department. Over 1.5 million people reside in the Austin Transitional Grant Area (TGA), which was established under the Ryan White Comprehensive AIDS Resources Emergency (CARE) Act and includes Bastrop, Caldwell, Hays, Travis and Williamson counties. Medicaid enrolls 7.3 percent of the Austin TGA and nearly 25 percent of the population does not have public or private health insurance. For individuals living with HIV/AIDS in the Austin TGA, 49.9 percent are Caucasian, 24.8 percent are Latino, and 24.2 percent are African-American.

The settlement with the Austin orthopaedic surgeon was negotiated following OCR’s investigation of an administrative complaint filed by a Latino male patient living with HIV. The patient, a Medicaid beneficiary, sought medical treatment for a knee injury and informed the surgeon of his HIV status. The surgeon contended that if he performed surgery on the man’s knee (a bone-tendon-bone Reconstruction), blood would splatter and possibly expose him to HIV disease. Due to the patient’s HIV status, the Austin surgeon referred the patient to another surgeon located over 200 miles away.

OCR found that the Austin surgeon violated Section 504 by refusing to perform the surgery and instead referring the patient to another surgeon. In making its determination, OCR relied on the expert opinion of a physician and medical epidemiologist from the National Center for Infectious Diseases at HHS’ Centers for Disease Control and Prevention (CDC). The CDC expert opined that practicing effective “universal precautions” — medical guidelines for the prevention and management of exposures to blood and body fluids — would have been the appropriate course of action for the Austin surgeon, instead of refusing to perform the surgery.

“At CDC, we are committed to ensuring that HIV/AIDS treatment decisions are based on the latest scientific evidence,” said Thomas R. Frieden, M.D., M.P.H., director of the CDC. “We appreciate the opportunity to provide expert consultation on the risks of HIV exposure in health care settings.”

Under the settlement, the Austin surgeon will receive comprehensive training on current HIV treatment protocols, universal precautions, and infection control procedures. The Texas/Oklahoma AIDS Education and Training Center, funded by HHS’ Health Resources and Services Administration (HRSA), has offered to provide the Austin surgeon with interactive, hands-on training and on-site clinical consultation. HRSA’s AIDS Education and Training Centers (AETC) Program supports a network of 11 regional centers (and more than 130 local performance sites) that conduct targeted, multi-disciplinary, free and low-cost training to health care professionals working with existing and emerging populations affected by HIV.

HRSA Administrator Mary Wakefield, Ph.D., R.N., stated, “We are pleased that one of our AIDS Education and Training Center grantees has offered this service to a health care professional as part of an OCR settlement agreement. A key part of our mission is improving the quality of care received by patients living with HIV/AIDS and providing high quality education and training to health care professionals is an essential part of that effort.”

A copy of the OCR letter of finding and the settlement agreement, along with more information about OCR’s other civil rights enforcement activities, can be found here. In addition, an explanation of who is a qualified individual with a disability may be found here.

Source
HHS

Mothers receiving highly active antiretroviral therapy (HAART) to treat HIV-1 infection are less likely than untreated mothers to transmit the virus to their newborns through breastfeeding, according to a new study. The findings, now available online in the Nov. 15 issue of The Journal of Infectious Diseases, suggest HAART regimens should be initiated as early as possible in eligible mothers in areas with limited resources, such as Africa, where most infant HIV-1 infections occur, and breastfeeding is common.

Led by Taha E. Taha, MBBS, PhD, of Johns Hopkins University Bloomberg School of Public Health, the researchers studied 2,318 infant/mother pairs in Malawi; a total of 130 infants (about 6 percent) became HIV-1-infected. The protective effect of HAART was readily apparent: The therapy was associated with an 82 percent reduction in postnatal HIV-1 transmission. The reduction was observed in mothers with CD4 counts low enough to be eligible for HAART compared to mothers with low counts who did not receive the therapy. Among the infants who became HIV-1-infected, only five had mothers who were both eligible for HAART and actually received it, representing a transmission rate of 1.8 percent. In contrast, 53 infected infants had mothers who were HAART-eligible but who went untreated (a 10.6 percent transmission rate). Seventy-two other infected infants had mothers who were HAART-ineligible because their CD4 cell counts were consistently high (a 3.7 percent transmission rate).

While acknowledging more research is needed to develop safe, effective, and affordable ways to prevent postnatal transmission in settings with few resources, the study’s authors recommend that women presenting late in pregnancy who have low CD4 counts and require antiretroviral treatment start HAART as soon as possible during pregnancy or postpartum. For women who do not need HAART for their own health because of a high CD4 count - and who represented approximately 70 percent of the Malawi patients studied - the investigators noted that the choices are unclear. The options include prolonged infant antiviral prophylaxis beyond 14 weeks of age or the institution of HAART in mothers who do not require the therapy according to current guidelines.

The authors had reported in 2008 that daily use of either nevirapine or nevirapine and zidovudine from birth up to the age of 14 weeks in breastfeeding infants of HIV-1-infected mothers reduced the rate of infant infection by 67 percent, compared to infants who received only a single dose of nevirapine and one week of zidovudine.

In an editorial accompanying the authors’ latest article, Grace C. John-Stewart, MD, PhD, of the University of Washington School of Public Health, noted that programs to prevent mother-to-child transmission of HIV need to accelerate in many ways. Globally, there are still large gaps in HIV-1 testing and CD4 count availability, which are necessary to identify women infected with the virus and determine if HAART is right for them. “Recognizing the impact of prompt HAART initiation in eligible women and finding efficiencies in CD4 testing and delivery of HAART services will leverage antenatal HIV-1 testing to increase maternal survival and decrease infant infections,” Dr. John-Stewart said.

Source:
John Heys

Infectious Diseases Society of America

From January 27, HIV and sexual health charity Terrence Higgins Trust (THT) will be running a new three month City & Guilds course in understanding HIV and AIDS. The distance learning based course is structured into three units with two face to face study days held in central Manchester and 20 hours of study time for each unit.

The qualification is designed for people interested in HIV and AIDS or working in a role where knowledge of the issue would be beneficial to their work. It’s ideal for people who work in a variety of roles including nurses, GP reception staff, voluntary workers, probation officers, police officers, teachers, social services staff, staff in drug support services and residential care services as well as interested individuals.

Joanna Hurren Head of Function at City & Guilds said “The course could help to open the door to a career in the HIV sector. Alternatively, it could help to support a person’s career development if they are already working in a role where it’s beneficial to be aware of the issues relating to HIV and AIDS.”

Areas of study on the course include:

- Transmission and prevention of HIV
- Stigma and discrimination in HIV and AIDS
- Managing HIV and AIDS

Jackie Redding, Director of Social Care and Service Development for THT said: “We’re delighted to be running this course in Manchester. It aims not only to raise awareness of HIV but also to reduce the stigma that still exists. I’d encourage anyone interested to get in touch and find out more.”

To sign up for the course or get further information visit http://www.tht.org.uk/cityandguilds.

Notes

City & Guilds is the expert and leading authority in vocational education and training - both in the UK and beyond. In operation for the last 130 years, City & Guilds is the UK’s leading awarding body for work-related qualifications. Twenty million people in the UK have City & Guilds qualifications, and the organisation awards a further 1.5 million qualifications to learners every year.

Source
Terrence Higgins Trust

The International AIDS Vaccine Initiative (IAVI) announced that it has signed a memorandum of understanding with the Ragon Institute to accelerate the development of new and promising AIDS vaccine candidates for testing. Formed in February 2009, the Ragon Institute was officially established at Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard University to help bring fresh perspectives and encourage cross-disciplinary collaborations to contribute to the discovery of an HIV/AIDS vaccine.

As part of this partnership, the Ragon Institute and IAVI will work together to identify promising concepts generated by the Institute that can be further developed and ultimately advanced to clinical trials with technical support from IAVI. In addition, this partnership is intended to facilitate productive exchanges among leading researchers affiliated with both IAVI and its network of scientific consortia and the Ragon Institute.

“We are honored to be working with the Ragon Institute and hope that this collaborative approach will take us a step further in devising new vaccine strategies and candidates to defeat HIV,” said Seth Berkley, MD, President and CEO of IAVI. “AIDS knows no boundaries, and neither should the scientists working to develop a vaccine to bring an end to one of the world’s leading killers.”

“This partnership offers great promise to help accelerate progress towards developing a vaccine to stop the AIDS pandemic,” said Phillip T. Ragon, who together with his wife Susan provided the funding to establish the Ragon Institute. “With declining interest in vaccines by pharmaceutical companies, public- private product development partnerships (PDPs) like IAVI have become a critical resource. This partnership will be indispensable in providing the speed, flexibility and technical expertise to advance promising early-stage concepts that will arise from the scientists at the Ragon Institute. As someone personally committed to helping solve the AIDS problem, I am excited to have this relationship with IAVI to help us move forward with the greatest possible speed.”

According to the Global Forum for Health Research, PDPs play an important role in addressing the widening gap in the availability of medicines and vaccines for neglected diseases. PDPs bring together skills, knowledge and resources from a variety of sectors including academia, nongovernmental organizations, philanthropists, government and intergovernmental agencies, as well as members of the for-profit private sector such as pharmaceutical and biotech companies, and apply them to solving some of the major global health challenges facing us today.

“Traditionally, it has been very difficult to convince the private sector to invest in medicines and vaccines for neglected diseases,” said Bruce Walker, MD, an MGH physician-investigator and director of the Ragon Institute. “I look forward to addressing this critical gap in AIDS vaccine discovery with IAVI, which has the technical expertise that will enable us to quickly advance the best concepts coming out of the Ragon Institute into clinical trials.”

Source
IAVI

People who smoke crack cocaine are at increased risk of becoming HIV-infected, report researchers in a new CMAJ (Canadian Medical Association Journal) study. The study also found that smoking crack cocaine has dramatically increased over the last several years.

These findings point to the urgent need for innovative public-health programs targeted at crack cocaine smokers.

The study looked at 1048 injection drug users participating in the Vancouver Injection Drug Users Study in Vancouver, British Columbia. Almost 36% of participants were female, 26% self-identified as Aboriginal and the median age at the start of the study was 34 years. The participants were HIV negative at enrolment but by the end of the 9 year study, 137 people contracted HIV.

In addition, the proportion of people who smoked crack cocaine daily jumped from 11.6% in the first 3 ½ year period to 39.7% in the last period.

“We have observed that use of crack cocaine has become one of the strongest risk factors for HIV seroconversion in Vancouver,” stated Dr. Evan Wood of the BC Centre for Excellence in HIV/AIDS. Study authors suggest this could be because of mouth wounds caused from crack pipes which make people more vulnerable to infection, or association with more HIV-positive individuals, which could increase likelihood of HIV infection through sex and needle sharing. However, they were unable to assess these possible risk factors in the study.

The authors urge adoption and rigorous evaluation of innovative - but controversial - harm reduction programs to help crack cocaine smokers, such as distribution of safer crack kits and provision of safe inhalation rooms. These interventions would provide opportunities for health workers to engage with crack smokers and help address their other health care needs.

In a related commentary, Dr. David Celentano and Dr. Susan Sherman of Johns Hopkins Bloomberg School of Public Health write that “with the increasing proportion of injection drug users who are smoking crack cocaine, harm reduction programs need to address the unique needs of these people as part of a comprehensive HIV prevention strategy. Although controversial, the distribution of “crack kits” (glass stem with mouth piece, metal screen, lip balm and hand wipes) to this population has the potential to reduce HIV transmission.”

Link to paper

Link to commentary

Source
Canadian Medical Association Journal

HIV and sexual health charity Terrence Higgins Trust is launching a new information pack today aimed at gay men recently diagnosed with HIV. The pack which is called ‘What Next?’ is a handy pocket sized guide and contains information on a selection of the support services that THT and other organisations provide.

In 2008, around 2,800 gay men were diagnosed with HIV in the UK but when diagnosed, many people feel quite alone. To address this, the pack contains information on issues such as finding out you have HIV, ways of telling people that you are HIV positive, health, dealing with medical staff and information on HIV, treatment and transmission.

Men can pick up a pack for free by contacting 020 7812 1783 or by emailing stephen.adair@tht.org.uk “What Next?’ is also available for sexual health clinics to order free in bulk either with or without the inserts. The aim is to give GUM clinics the option to include information about their own services as well as others in their region - giving men an information pack that’s specific to their needs and their location.

THT is calling for GUMs and other sexual health clinics to stock the information packs so that as many men as possible can find out about the support that’s available for them, whether it’s counselling, advice about treatment, or simply being able to talk to someone for confidential advice and support.

Alan Wardle, Head of Health Promotion at Terrence Higgins Trust said “Being diagnosed with HIV can make people feel like they’re on an emotional roller coaster. Many people are left feeling quite alone or feel like they have hundreds of questions to ask. This pack aims to give some practical information that gay men might want after they’ve been diagnosed. Crucially it gives contact details of organisations that can offer support and information at a time when it might be most needed.”

Dr Christian Jessen presenter of Channel 4’s Embarrassing Illnesses said: “The ‘What Next?’ information pack is an essential tool kit for any gay man who has recently been diagnosed with HIV. There are so many things to take on board when you’ve been diagnosed and sometimes you may not be able to take it all in initially. Having a pack that you can take away and read when you’re ready is a great idea.”

The information pack follows the successful launch of the interactive website ‘What next?’ which provides information and support specifically for newly diagnosed gay men.

Source
Terrence Higgins Trust

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