Although much work remains to be done, a United Nations global reporting system on HIV/AIDS has already yielded an “unequaled wealth of data” on progress toward meeting UN targets for responding to the global HIV epidemic. An update on the development of the UN General Assembly Special Session on HIV/AIDS (UNGASS) global reporting system appears in a special supplement to JAIDS: Journal of Acquired Immune Deficiency Syndromes. JAIDS is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals, and institutions in medicine, nursing, allied health, and pharmacy.

The UNGASS system provides “a good indication of the overall progress in the global response to HIV”-including whether the world community is on track to meet the UN’s ambitious timetable for turning the tide in the fight against HIV. Guest editors of the special supplement are Deborah Rugg, PhD, of The Joint United Nations Programme on HIV/AIDS (UNAIDS), Michel Carel, PhD, of Free University Brussels, and Hein Marais, an Independent Writer in Johannesburg, South Africa.

UNGASS Process a ‘Catalyst’ for Development of National HIV Monitoring Systems

The 11 articles in the supplement provide a look into the development of the UNGASS global reporting system, being implemented as part of the 2001 UNGASS Declaration of Commitment on HIV/AIDS. The UNGASS system provides a framework for biennial Country Progress Reports, which will be used to assess attainment of the UN’s Millennium Development Goal (MDG) 6: halting and reversing the HIV epidemic by 2015.

As of 2008, the UNGASS system included data from 147 countries-through the first three rounds of reporting, response rates increased from 54 to 77 percent. The reports have provided unprecedented data on patterns of HIV epidemics, behaviours related to the spread or control of HIV, and progress in implementing programmes essential to meeting the MDG 6 targets.

Several articles present preliminary analyses of data on the global response to the HIV epidemic. At this point-midway to the 2015 deadline for MDG 6-the data show “limited progress” in most areas:

- Only about 40 percent of young men and women worldwide know how to protect themselves from acquiring HIV (compared to a 2010 target of 95 percent).

- Programmes to prevent transmission of HIV from mothers to infants reach only 33 percent of those in need (target 80 percent).

- Rates of new infections in infants born to HIV-positive mothers have decreased by only 25 percent (target 50 percent)

- The 2010 goal for financial investment in AIDS responses-$10 billion-has been met. However, there are concerns about the sustainability of this response, given the global economic recession.

The UNGASS HIV monitoring system also appears to make progress toward another key goal: for countries to “achieve ownership” of the national HIV reporting process. “Countries have come to regard the UNGASS process as more than a reporting exercise at the UN General Assembly,” Dr. Rugg and her co-editors write. They believe the UNGASS system has promoted “public accountability” in confronting the HIV epidemic.

Although the establishment of a global HIV reporting and monitoring system is a major accomplishment, many complex issues remain to be addressed. The data collected so far suggest that HIV prevention and treatment programmes will need to be “dramatically scaled up” if worldwide goals are to be met. Yet, as evidenced by the papers in the JAIDS supplement, ” The reporting system has provided a catalyst for the development of national systems for monitoring and evaluating HIV programmes and for guiding more effective, efficient, and sustainable responses to the HIV epidemic,” Dr. Rugg and colleagues conclude.

About JAIDS

JAIDS: Journal of Acquired Immune Deficiency Syndromes is the trusted, interdisciplinary resource for HIV- and AIDS-related information with a strong focus on basic science, clinical science, and epidemiology. Co-edited by the foremost leaders in clinical virology, molecular biology, and epidemiology, JAIDS publishes vital information on the advances in diagnosis and treatment of HIV infections, as well as the latest research in the development of therapeutics and vaccine approaches. This ground-breaking journal brings together rigorously peer-reviewed articles, reviews of current research, results of clinical trials, and epidemiologic reports from around the world.

Source
Lippincott Williams & Wilkins

Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced that data from the University of Pennsylvania investigator sponsored Phase 1 safety study of Sangamo’s zinc finger nuclease (ZFN) based product, SB-728-T, for HIV/AIDS were inadvertently and prematurely disclosed on the internet.

Data were presented in a student course at the University of Pennsylvania School of Medicine from a single subject treated with SB-728-T who, as part of the study, began a structured treatment interruption (STI) from his antiviral drug therapy four weeks after SB-728-T treatment. This subject was reported to have stable CD4+ and ZFN-modified T-cell levels and an undetectable viral load one month post STI initiation. Previous studies have shown that in subjects undergoing an STI, the average time to detection of an increase in viral load is two to four weeks. While this subject continues to demonstrate stable CD4+ T-cell counts and stable levels of ZFN-modified T-cells, by six weeks post STI initiation the subject had a detectable viral load.

As previously stated, the company and the University of Pennsylvania intend to provide updates on the two ongoing Phase 1 SB-728-T trials only at appropriate scientific or medical meetings.

About Sangamo

Sangamo BioSciences, Inc. is focused on the research and development of novel DNA-binding proteins for therapeutic gene regulation and modification. The most advanced ZFP Therapeutic(TM) development program is currently in Phase 2 clinical trials for evaluation of safety and clinical effect in patients with diabetic neuropathy and ALS. Sangamo also has two Phase 1 clinical trials to evaluate safety and clinical effect of a ZFP Therapeutic for the treatment of HIV/AIDS. Other therapeutic development programs are focused on cancer, neuropathic pain, nerve regeneration, Parkinson’s disease and monogenic diseases. Sangamo’s core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). By engineering ZFPs that recognize a specific DNA sequence Sangamo has created ZFP transcription factors (ZFP TF) that can control gene expression and, consequently, cell function. Sangamo is also developing sequence-specific ZFP Nucleases (ZFN) for gene modification. Sangamo has established strategic partnerships with companies in non-therapeutic applications of its technology including Dow AgroSciences, Sigma-Aldrich Corporation.

This press release may contain forward-looking statements based on Sangamo’s current expectations. These forward-looking statements include, without limitation, references to the clinical trials of SB-728-T, research and development of novel ZFP TFs and ZFNs and therapeutic applications of Sangamo’s ZFP technology platform. Actual results may differ materially from these forward-looking statements due to a number of factors, including uncertainties relating to the completion of stages of the SB-728-T clinical trials, whether the SB-728-T clinical trials will validate and support tolerability and efficacy of SB-728-T, technological challenges, Sangamo’s ability to develop commercially viable products and technological developments by our competitors. See Sangamo’s SEC filings, and in particular, the risk factors described in the company’s Annual Report on Form 10-K and most recent Quarterly Report on Form 10-Q. Sangamo BioSciences, Inc. assumes no obligation to update the forward-looking information contained in this press release.

Source: Sangamo BioSciences, Inc

Since the discovery in 2007 that a component of human semen called SEVI boosts infectivity of the virus that causes AIDS, researchers have been trying to learn more about SEVI and how it works, in hopes of thwarting its infection-promoting activity.

Now, scientists at the University of Michigan have determined the atomic-level, three-dimensional structure of a SEVI precursor known as PAP248-286 and discovered how it damages cell membranes to make them more vulnerable to infection with HIV. The work is described in two new papers. The most recent, describing the structure, was published online Nov. 17 in the Journal of the American Chemical Society. The paper describing how PAP248-286 interacts with cell membranes appeared in the Nov. 4 issue of Biophysical Journal.

PAP248-286 is a peptide—a chain of amino acids not long enough to be considered a protein. Individual PAP248-286 peptides have a tendency to clump together to form amyloid fibers called SEVI (semen enhancer of viral infection). Amyloid fibers are of great interest because they are the calling cards of many neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, and aging-related diseases like type-2 diabetes. Using NMR (nuclear magnetic resonance) spectroscopy, a technique that not only yields atomic-level details of a molecule’s structure, but also shows how the molecule nestles into the membrane with which it interacts, researcher Ayyalusamy Ramamoorthy and coworkers found that the structure of PAP248-286 is unlike that of most other amyloid-forming peptides and proteins.

In solution, SEVI is completely unstructured or has no definite shape and is therefore ineffective. On the other hand, “when bound to the membrane, it’s in a spaghetti-like arrangement—a disorganized, loose coil,” said Ramamoorthy, a professor of chemistry and of biophysics. In contrast, most other amyloid proteins assume a more ordered, helical configuration. Also unlike other amyloid peptides, SEVI does not penetrate deep into the greasy region of the cell membrane, but is located near the surface. Ramamoorthy and coauthors believe the spread-out, disordered configuration and its location in the cell membrane may explain the ability of SEVI fibers to enhance HIV infection, as the arrangement provides more surface area with which the virus can interact.

A key finding of the second study is that PAP248-286 “shocks” the membrane, inducing a structural change—a kind of dimple that allows HIV to attach to and enter the cell.

Next, Ramamoorthy and colleagues hope to discern more structural details of PAP248-286 and SEVI. They also plan to screen antioxidant compounds such as green tea extract, curcumin and resveratrol (found in red wine) to see if such compounds are capable of blocking SEVI’s HIV-enhancing activity.

Ramamoorthy’s coauthors on the Journal of the American Chemical Society paper are graduate student Ravi Nanga, post-doctoral fellows Jeffrey Brender and Nataliya Popovych and NMR specialist Subramanian Vivekanandan. His coauthors on the Biophysical Journal paper are Brender, graduate student Kevin Hartman, former post-doctoral fellow Lindsey Gottler, former graduate student Marchello Cavitt and biophysics undergraduate student Daniel Youngstrom.

This research was supported by funds from the National Institutes of Health.

Source: Nancy Ross-Flanigan

University of Michigan

WHAT: New discoveries about anti-HIV antibodies may bring researchers a step closer to creating an effective HIV vaccine, according to a new paper co-authored by scientists at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Scientists know that an HIV-neutralizing antibody called b12 binds to gp120, an HIV surface protein, at one of the few areas of the virus that does not mutate: the site where gp120 initially attaches to human immune cells (http://www3.niaid.nih.gov/news/newsreleases/2007/b12antibody.htm). It was thought that exposing the human immune system to this site on gp120 would generate antibodies that, like b12, can neutralize HIV. Studies have found that for unknown reasons, however, the vast majority of antibodies that recognize this site do not block the virus from infecting cells. Now a new study solves this puzzle, suggesting that antibodies must home in precisely on the site of initial gp120 attachment to successfully neutralize HIV.

The gp120 protein usually appears on the surface of HIV and on infected cells in inactive forms of viral debris or non-functional viral spikes. Only rarely do gp120 molecules appear on the surface of the virus in a functional viral spike, which contains a cluster of three gp120 molecules, known as a trimer, in specific alignment. HIV uses this functional viral spike to bind to immune cells and infect them.

The new study shows that most antibodies able to bind to non-functional forms of gp120 cannot bind to gp120 in the functional viral spike and therefore cannot neutralize HIV. Further, the study demonstrates that the reason most anti-gp120 antibodies similar to b12 cannot bind to the functional viral spike is because of the way these antibodies attach to gp120. A close examination of two such antibodies illustrated that their binding positions on gp120 cause a key portion of the protein either to swing in or flare out in positions incompatible with the trimer structure. In contrast, the position of b12 antibody binding allows gp120 to neatly form its normal trimeric structure.

The scientists conclude that generating HIV neutralizing antibodies will require teaching the immune system to make antibodies that precisely target the site of vulnerability on gp120 as it appears in the functional viral spike rather than targeting the plentiful forms of viral debris such as single gp120 molecules.

ARTICLE: L Chen et al. Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. Science DOI 10.1126/science.1175868 (2009).

WHO: Peter D. Kwong, Ph.D., and John R. Mascola, M.D., chiefs of the Structural Biology Section and BSL-3 Core, respectively, in the NIAID Vaccine Research Center, as well as Gary J. Nabel, M.D., Ph.D., director of the Vaccine Research Center.

Source: Laura Sivitz

NIH/National Institute of Allergy and Infectious Diseases

HIV and sexual health charity Terrence Higgins Trust (THT) is calling for people across Shropshire, Telford & Wrekin to get involved in World AIDS Day (December 1) this year, either by attending an event, making a donation to support local HIV services, or wearing a red ribbon to raise awareness.

World AIDS Day, which has been running every December since 1988, is dedicated to raising awareness of HIV and AIDS. In the UK alone, over 80,000 people are living with HIV and over 7,000 are diagnosed every year.

The following events, run in collaboration with Shropshire Buddies & Body Positive, are taking place in Shropshire, Telford & Wrekin for World AIDS Day:

- County-wide Awareness Drive (various times and locations across Shropshire)
Friday 27 November (10.00am - 2.00pm): Newport High Street
Saturday 28 November (10.00am - 1.00pm): Wellington High Street
Saturday 28 November (9.00am - 6.00pm): Telford Shopping Centre
Tuesday 1 December (9.00am - 6.00pm): Pride Hill Shopping Centre, Shrewsbury
Saturday 5 December (10.00am - 1.00pm): Ludlow Market
THT staff and volunteers will be out in force at locations across Shropshire in the run up to and immediately after World AIDS Day, raising awareness of HIV, collecting donations, and handing out red ribbons.

- Tuesday 1 December (10.00am - 5.00pm): Day of Remembrance, St Laurence Church, Ludlow
St Laurences Church will be open all day for people to light a candle in remembrance and celebration, with an hour-long vigil from 12.00pm - 1.00pm. THT will provide a display with information on HIV and how to prevent it. The day will conclude at 4.45pm with prayers of remembrance.

- Tuesday 1 December (6.30pm - 8.00pm): Candle-Lit Vigil, The Square, Shrewsbury
THT will be holding a special candle-lit vigil to remember those that have died and to celebrate the lives of those with HIV today. The vigil is open to all, and will feature a reading by Reverend Mark Thomas, a performance by Heart and Soul Community Choir, and a two minute silence.

Lotte Hakeman, Centre Manager for THT in Shropshire, said “World AIDS Day is one of the most important events in THT’s calendar. Currently in the UK one in four people with HIV don’t know they have it, so it’s vital that we continue to raise awareness. We hope local people will get involved in some way, either by attending an event, making a donation, or just wearing a red ribbon.”

Source
Terrence Higgins Trust

HIV and sexual health charity, Terrence Higgins Trust (THT) is calling for people in Sandwell to get involved in World AIDS Day (December 1) this year, either by attending an event, making a donation to support local HIV services, or wearing a red ribbon to raise awareness.

World AIDS Day, which has been running every December since 1988, is dedicated to raising awareness of HIV and AIDS. In the UK alone, over 80,000 people are living with HIV and over 7,000 are diagnosed every year.

The following events are taking place in Sandwell for World AIDS Day this year:

- Saturday 21 November (3.00pm - 6.00pm): Open forum on HIV for English-speaking Africans
At THT’s Sandwell centre (290-292 High Street), there will be a special session for English-speaking Africans living locally, providing basic facts about how people can protect themselves from HIV, answering questions, and giving general information on World AIDS Day.

- Friday 27 November (3.00pm - 6.00pm): Open forum on HIV for French-speaking Africans
At THT’s Sandwell centre (290-292 High Street), there will be a special session for French-speaking Africans living locally, providing basic facts about how people can protect themselves from HIV, answering questions, and giving general information on World AIDS Day.

- Tuesday 1 December (10.00am - 4.00pm): Awareness drive, West Bromwich high street
Staff and volunteers from THT will be out in force on West Bromwich High Street, raising awareness of HIV, providing information on safer sex and giving out red ribbons.
Jane Morel, Regional Manager for THT in the West Midlands, said: “World AIDS Day is one of the most important events in THT’s calendar. Currently in the UK one in four people with HIV don’t know they have it, so it’s vital that we continue to raise awareness. We hope local people will get involved in some way, either by attending an event, making a donation, or just wearing a red ribbon.”

Source
Terrence Higgins Trust

HIV and sexual health charity, Terrence Higgins Trust (THT) is calling for people in Swindon to get involved in World AIDS Day (December 1) this year, either by attending an event, making a donation to support local HIV services, or wearing a red ribbon to raise awareness.

World AIDS Day, which has been running every December since 1988, is dedicated to raising awareness of HIV and AIDS. In the UK alone, over 80,000 people are living with HIV and over 7,000 are diagnosed every year.

Steve Jones, Regional Manager for THT in the South West, said: “World AIDS Day is one of the most important events in THT’s calendar. Currently in the UK one in four people with HIV don’t know they have it, so it’s vital that we continue to raise awareness. We hope local people will get involved in some way, either by attending an event, making a donation, or just wearing a red ribbon.”

Source
Terrence Higgins Trust

‘Prevention is the best cure’ is a common expression, but what happens if preventative measures are not used? A large proportion of pregnant Ugandan women are going out of their way not to be HIV tested, increasing the risk of mother-to-child transmission.

A recent paper by Larsson et al. in AIDS journal discussed how mother-to-child transmission of HIV can be easily and cost-effectively prevented using a short course of antiretroviral therapy. However, this is effective only if the mother is willing to be screened for HIV.

Anne Buve, a member of Faculty of 1000 Medicine, discusses the recent and “worrying” findings of this study, which she describes as “quite sobering”. There is currently an opt-out policy for HIV testing even though the HIV prevalence in Uganda is 6.4%.

One year after the implementation of the opt-out policy, fewer than 60% of pregnant women were tested for HIV in 2007 in the majority of countries in Eastern and Southern Africa, the exception being Botswana where voluntary counseling and subsequent testing rates are higher.

Programmes of syphilis screening during pregnancy already faced the same problem in Uganda. However, the authors of the study suggest that women who attended an antenatal clinic that did not have HIV testing on site, did so in order to avoid HIV testing. If confirmed, this finding is worrying.

More studies that identify and tackle the problems that exist with HIV screening need to be carried out, especially in parts of the world that have a high prevalence of HIV. Dr Buve goes on to say, “there should be more studies like this one that look into why people do not have access to or refuse to accept interventions that could prevent HIV infection among their offspring”.

Source: Steve Pogonowski

Faculty of 1000: Biology and Medicine

IV is a virus related to HIV that can infect monkeys. In some strains of monkey (which are known as natural hosts) SIV does not cause disease, whereas it does in others (which are known as susceptible hosts). It is hoped that understanding why SIV does not cause disease in natural hosts will provide insight into how to control HIV infection of humans. Two independent research teams, one led by Michaela C. Müller-Trutwin, and the other led by Guido Silvestri, Ashley Haase, and David Kelvin, have now determined that SIV induces vigorous activation of the immune system, in particular upregulation of genes stimulated by immune molecules known as IFNs, in both natural and susceptible hosts, but strikingly, the responses are later brought under control only in the former. In an accompanying commentary, Nina Bhardwaj and Olivier Manches, at New York University Langone Medical Center, New York, discuss how the lessons learned from these studies might impact HIV vaccine design and therapy.

TITLE: Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys

View this article at: http://www.jci.org/articles/view/40115?key=oNmMSIkn4H9JdUJ72v6a

ACCOMPANYING ARTICLE
TITLE: Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response

View this article at: http://www.jci.org/articles/view/40093?key=8rqR89T5BZYeJ7KuHW55

ACCOMPANYING COMMENTARY
TITLE: Resolution of immune activation defines nonpathogenic SIV infection

View this article at: http://www.jci.org/articles/view/41509?key=YH73bnLajqEZK6CETk0O

Source: Karen Honey

Journal of Clinical Investigation

Ohr Pharmaceutical Inc. (OTCBB: OHRP) is developing OHR/AVR118 for treatment of cachexia based on technology acquired earlier this year from Advanced Viral Research Corp. OHR/AVR118 has shown excellent therapeutic efficacy and safety in human clinical trials in over 100 patients with applications for cachexia in Cancer and AIDS patients, as well as Rheumatoid Arthritis. OHR/AVR118 is a unique immunomodulator that affects the synthesis of chemokines and cytokines. Its main action is anti-inflammatory through the inhibition and modulation of cellular pro-inflammatory chemokine and cytokine synthesis, especially tumor necrosis factor-alpha (TNF-alpha). Moreover, the drug acts to maintain immune homeostasis. It prevents the very destructive and toxic cytokine showers that result from certain viral infections such as influenza and many cancers, including the chemotherapeutic drugs and radiotherapy given to shrink tumors. As would be expected based on its molecular immunomodulating properties and mechanism of action, Ohr118 has also shown efficacy in the treatment of the important auto-immune disease Rheumatoid Arthritis.

In an early Phase 2 open-label, dose-escalation trial of 32 cachecic patients suffering with AIDS or cancer, OHR/AVR118 was administered subcutaneously at doses of 0.4 to 4 ml/day for 28 days (6 days/week). All dose groups showed an increase in weight, strength and fat percentage, with more significant improvements in the two higher dose levels. All patients with anorexia at entry became anorexia-free after three weeks of therapy, with the higher dosing cohorts exhibiting an average positive weight gain. Patients in the highest dosing cohort increased their average weight by 2.2 pounds over four weeks of treatment and this effect continued through the following four weeks at which point the average weight had increased by 2.6 pounds over baseline. All patients in this cohort also showed an increase in fat percentage which was sustained after treatment discontinuation in all patients. All patients reported an increase in daily activity and 80 percent of the patients reported decreased fatigue. Spontaneous patient comments reflect widespread dose-related improvements in Quality of Life (QOL). OHR/AVR118 showed a very favorable safety profile with no major adverse effects in the trial, building upon its strong safety profile in other human and animal studies.

An earlier randomized double blind clinical study enrolled 43 cachecic HIV-infected adults naive to anti-retroviral therapy. A total of 21 patients received OHR/AVR118, and 22 patients received a placebo. Dosing was two 1ml subcutaneous injections daily on the first 14 days, followed by one daily 1ml dose on days 22-28, 36-42 and 50-56. The follow up period lasted until day 120. At the end of the follow up period, there was a statistically significant increase in CD4 positive cell counts (p=.014) in the OHR/AVR118 treated patients. The treated patients experienced a mean weight increase (p=.003) while the placebo group experienced a mean weight loss. No toxic effects were observed in any of the patients who received OHR/AVR118. There was a trend towards higher CD8 cell counts, lower viral loads and fewer opportunistic infections in the OHR/AVR118 treated group.

Recognizing the tremendous potential for OHR/AVR118 to become the standard of care for Cancer and AIDS patients suffering from Cachexia, Ohr is dedicated to continue the development of OHR/AVR118. Currently, OHR/AVR118 is in an open-label late Phase 2 trial being conducted at McGill University for the treatment of Cachexia in Cancer patients.

Source
Ohr Pharmaceutical, Inc.

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