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