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Category: Completed Research
Forum: FightAIDS@Home
Thread: Interesting news articles about AIDS |
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Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
PRO 140 PRO 140 is a humanized monoclonal antibody developed by Progenics' scientists, designed to block HIV infection by inhibiting the virus' ability to bind to and enter immune system cells. As a monoclonal antibody PRO 140 is not expected to be metabolized by the liver and, as such, has the potential for a better tolerability profile than many approved therapies for HIV infection. Unlike small-molecule CCR5 antagonists, PRO 140 inhibits HIV entry at concentrations that in vitro do not appear to block CCR5's natural activity of directing the migration of immune cells towards sites of inflammation in the body. PRO 140 was given "Fast Track" designation by FDA, a formal process which facilitates development and expedites regulatory review of drugs intended to address unmet medical needs for serious or life-threatening conditions. How PRO 140 works PRO 140 prevents HIV from entering healthy immune system cells by binding to a distinct site on the cellular co-receptor CCR5; one of two receptors required for HIV entry into susceptible cells -- the other is the T-Cell CD4. CCR5's role in HIV infection was characterized by Progenics and its collaborators in 1996.1 (Some strains of HIV use the CXCR4 co-receptor as a portal of entry either exclusively or alternatively with CCR5 and are therefore not inhibited by PRO 140). Through its surface glycoprotein 120 ("GP120"), HIV first binds to CD4, and then binds to either the CCR5 or CXCR4 co-receptor, thus enabling conformational changes that permit fusion of the virus with the cell membrane, and facilitate entry of the viral genetic information into the cell and subsequent viral replication. By binding to CCR5 first, PRO 140 blocks HIV from binding to CCR5 and fusing with the cell membrane, thereby inhibiting the viral replication process. 1 Dragic, et al. Nature. 381, 667-673 (1996) http://www.progenics.com/prod_pro140.cfm PRO 140 is currently in phase 2 clinical testing for the treatment of HIV infection. Thanks very interesting. |
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Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
From The White House
Obama Announces National HIV/AIDS Community Discussions President Obama today announced the launch of the National HIV/AIDS Community Discussions, a series of events to be held across the country. These events, hosted by the White House Office of National AIDS Policy (ONAP) will offer the public a chance to provide input as the White House works to fulfill the President’s pledge to develop a National HIV/AIDS Strategy (NHAS). The first event, the Atlanta HIV/AIDS Community Discussion, will be held on August 25th at the 2009 National HIV Prevention Conference. "HIV remains an serious challenge to the American people and I am committed to developing an effective National HIV/AIDS Strategy," said President Obama. "The National HIV/AIDS Community Discussions will provide an opportunity for members of the public to give their input on how we can best address this crucial issue. With the insights from communities across the country, we will have a strategy that is focused on the goals of reducing HIV incidence, getting people living with HIV/AIDS into care and improving health outcomes, and reducing HIV-related health disparities." With more than 56,000 new HIV infections occurring in the United States each year, the President believes that we must re-focus national attention on the domestic epidemic. He has articulated three goals for the NHAS: reducing HIV incidence, increasing access to care and optimizing health outcomes, and reducing HIV-related health disparities. The national HIV/AIDS community discussions are just one mechanism for engaging the American people and obtaining input. The Presidential Advisory Council on HIV/AIDS (PACHA) will also provide input, and public comments submitted to the ONAP website will also be taken into consideration..... |
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Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
IRIN Films is pleased to announce the launch of “Heroes of HIV” – a powerful and moving new series of short films on HIV/AIDS.
The films profile the work of people involved in the fight against HIV/AIDS. Their stories are sometimes sad, sometimes uplifting, always inspiring. Click here to watch the films As usual we'd be grateful for any feedback you might have. Sheila Koskei IRIN Film Unit E-mail: sheila@irinnews.org Film page: http://www.irinnews.org/filmtv.aspx IRIN: http://www.irinnews.org |
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Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
aquiles_66 and other members
Let´s keep news abt AIDS in one place / thread please Thanks |
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Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
Entendido Jean Pierre.... desde chile también
 CpG Methylation Controls Reactivation of HIV from Latency ______________________________________________________ Abstract DNA methylation of retroviral promoters and enhancers localized in the provirus 5′ long terminal repeat (LTR) is considered to be a mechanism of transcriptional suppression that allows retroviruses to evade host immune responses and antiretroviral drugs. However, the role of DNA methylation in the control of HIV-1 latency has never been unambiguously demonstrated, in contrast to the apparent importance of transcriptional interference and chromatin structure, and has never been studied in HIV-1-infected patients. Here, we show in an in vitro model of reactivable latency and in a latent reservoir of HIV-1-infected patients that CpG methylation of the HIV-1 5′ LTR is an additional epigenetic restriction mechanism, which controls resistance of latent HIV-1 to reactivation signals and thus determines the stability of the HIV-1 latency. CpG methylation acts as a late event during establishment of HIV-1 latency and is not required for the initial provirus silencing. Indeed, the latent reservoir of some aviremic patients contained high proportions of the non-methylated 5′ LTR. The latency controlled solely by transcriptional interference and by chromatin-dependent mechanisms in the absence of significant promoter DNA methylation tends to be leaky and easily reactivable. In the latent reservoir of HIV-1-infected individuals without detectable plasma viremia, we found HIV-1 promoters and enhancers to be hypermethylated and resistant to reactivation, as opposed to the hypomethylated 5′ LTR in viremic patients. However, even dense methylation of the HIV-1 5′LTR did not confer complete resistance to reactivation of latent HIV-1 with some histone deacetylase inhibitors, protein kinase C agonists, TNF-α, and their combinations with 5-aza-2deoxycytidine: the densely methylated HIV-1 promoter was most efficiently reactivated in virtual absence of T cell activation by suberoylanilide hydroxamic acid. Tight but incomplete control of HIV-1 latency by CpG methylation might have important implications for strategies aimed at eradicating HIV-1 infection. link http://www.plospathogens.org/article/info%3Ad...71%2Fjournal.ppat.1000554 regards  |
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Dan60
Senior Cruncher Brazil Joined: Mar 29, 2006 Post Count: 185 Status: Offline Project Badges: 
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Drugs to Watch in 2009
Monday, March 16th, 2009 link by David Evans Experts think we’re about to enter a dry spell in terms of new HIV treatments, with no truly novel compounds available for treatment-experienced patients likely for the next several years. They remain hopeful, however, that new technologies and avenues of research could spark the next great leap forward. The science of HIV has been a mixed bag. The search for an effective vaccine has experienced one setback after another, and it has often seemed that we’re no closer to a cure today than we were when the virus was first discovered more than 25 years ago. But with treatment—drugs to achieve long-term management of the disease—we’ve hit the jackpot. Within the same 25 years, the U.S. Food and Drug Administration (FDA) has approved 20 different drugs, four of them in the past three years. Now, however, that run of riches has hit a snag. No completely innovative new treatment is in a stage of research beyond the earliest point in human testing—which means it will be several years before such a drug can be prescribed for highly treatment-experienced HIV-positive individuals who need them most. Experts who’ve been watching HIV drug development for nearly two decades universally expressed concern about the state of AIDS research and the possibility of no new drugs being available in the short term. They stated that the path to FDA approval has become more challenging for HIV treatments, compounded by the fact that the market has become more crowded with drugs that generally work quite well for many years. This doesn’t mean that researchers, or drug companies, have completely given up on HIV. Activists and researchers contacted by AIDSmeds say there are reasons to remain hopeful. It’s just that the treatments that look most interesting at this point are far from a sure bet, especially in an industry where most drugs that look promising in early studies don’t pan out in advanced clinical trials. Despite such a dreary short-term outlook, people do have hope for the future. The following is a roundup of experimental treatments—and novel ways to use some existing treatments—that several researchers and AIDS treatment activists identified as the most exciting drugs to watch in 2009. Closest to the Finish Line A handful of drugs that could work for heavily treatment experienced patients have made it over the hurdles of early drug development. They include two entry inhibitors known as ibalizumab and PRO 140; a nucleoside analogue reverse transcriptase inhibitor (NRTI) called amdoxovir; and bevirimat, a maturation inhibitor. All have made it through early Phase I testing and are either in clinical trials or entering studies to determine preliminary dosing, safety and effectiveness. IDX-899, purchased earlier this month by GlaxoSmithKline for further development, is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with potential for patients with HIV resistance to current NNRTIs. Old Dogs, New Tricks Bob Huff, who’s in charge of antiretroviral (ARV) advocacy at the Treatment Action Group (TAG) in New York City, says he’s most interested in “watching research on new strategies in antiretroviral treatment, chief among them combinations that do not use drugs from the nucleoside analogue [NRTI] class, or ‘nuke-sparing regimens.’” Huff points to studies that are either currently recruiting or about to get started that substitute either an integrase inhibitor like Isentress (raltegravir) or an entry inhibitor like Selzentry (maraviroc) for NRTIs like Truvada (tenofovir plus emtricitabine). He reasons that such drugs may be less likely to have long-term side effects, given the fact that NRTIs may actually damage cellular DNA. An avenue of research that excites Steven Becker, MD, an AIDS researcher and consultant to the pharmaceutical industry from Seattle, is new drug delivery technology. One in particular that he feels has promise is a special way of formulating the NRTI Viread (tenofovir) so that it is much more readily absorbed by the fat molecules on the surface of CD4 cells. This new formulation is being developed by Chimerix in cooperation with Viread’s maker, Gilead Sciences, and could allow doctors to use significantly lower doses of the drug, which could potentially reduce side effects. Becker also sees a great deal of promise in nanotechnology, which several companies are exploring as a way to make drugs that only have to be taken weekly or once a month. Bob Munk, a longtime treatment activist from New Mexico, says he is intrigued by a new immune-boosting drug that also has a novel delivery mechanism—through the skin. The drug, called DermaVir, is given via a transdermal patch similar to nicotine patches. It is currently in Phase II studies. Researchers hope that DermaVir can help train people’s CD4 and CD8 cells to more effectively fight HIV. New Supporting Characters Another type of drug that could breathe new life into some old standbys—as well as some newer drugs in the wings—is called a pharmacokinetic (PK) enhancer. These drugs are used solely to boost the blood levels of other drugs. Right now, the only drug of that type in use is Norvir (ritonavir), which also unfortunately boosts cholesterol and triglyceride levels—even at lower doses. Reported at the 16th Conference on Retroviruses and Opportunistic Infections that took place just last week in Montreal are two new PK enhancers, one from Gilead Sciences and the other from Sequoia Pharmaceuticals. Both companies presented data on their PK boosters from Phase I studies in HIV-negative volunteers. The studies were conducted to provide an early look at safety and proof that the drugs do what they are supposed to do. Gilead reports it’ll be developing its booster, called GS 9350, in tandem with its integrase inhibitor, elvitegravir (which currently requires Norvir boosting), and will package both in a four-in-one pill that also includes Truvada. It is possible that the Sequoia drug, called SPI-452, might also be coformulated with other HIV drugs that depend on a booster. Reversing Viral Sabotage The human immune system actually has a number of effective methods for controlling viral infections. One of these is a protein called APOBEC-3G. In recent years, scientists have discovered that APOBEC-3G is quite remarkable at stopping many viruses in the lentiviral family, which includes HIV, from reproducing. Such viruses have had to evolve their own proteins, called VIF proteins, to disable APOBEC-3G. David Margolis, MD, an AIDS researcher from the University of North Carolina in Chapel Hill, thinks that drugs that could counteract VIF have a lot of promise in the long term. He says he’ll be eagerly following research on APOBEC-3G and VIF in the coming year. Elite Control Another recent discovery is the role of a cell receptor called programmed cell death 1, or PD-1, in long-term survivors with HIV. Scientists think the receptor—which, when stimulated causes cells to self-destruct—is a vital component in protecting the body from diseases that cause the immune system to attack a person’s own body. It’s presence on virally infected cells, however, appears to have negative consequences, leading to a syndrome called T-cell exhaustion. In such cases the immune system can no longer adequately control the viral infection. A set of researchers who’ve been examining the characteristics of a group of people who manage to control HIV reproduction for long periods of time without ARV drugs—called elite controllers—found a characteristic in common: Their CD4 and CD8 cells tend not to have very many PD-1 receptors on their surface compared with people who do not control the virus well. Richard Jefferys, who heads up immune and vaccine research advocacy at TAG, is eager to see what will happen with a treatment that blocks PD-1. Just last year, researchers at Emory University in Atlanta found that the immune cells of monkeys infected with simian immunodeficiency virus (SIV) were far more effective when the monkeys were given an antibody that blocks PD-1. What’s more, the monkeys who got the antibody lived longer than monkeys who did not. Jefferys concedes that it’s a long way from monkeys with SIV to humans with HIV, but he’s hopeful about companies such as Medarex that are developing PD-1 antibodies for use against HIV and other diseases. |
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Papa3
Senior Cruncher Joined: Apr 23, 2006 Post Count: 360 Status: Offline Project Badges: 
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http://arstechnica.com/science/news/2009/08/l...degrees-of-separation.ars
Life's proteins related by seven degrees of separation Starting with a database of all known structural features in proteins, researchers have performed a network analysis based on their similarities. The surprising result is that almost every protein we know of is related to the rest by seven degrees of separation. By John Timmer | Last updated August 31, 2009 3:15 PM CTText Size Print this articleLeave a comment Argonne National Laboratory Life requires lots of chemicals, from the DNA and RNA that carry genetic information to the lipids that keep the contents of cells separated from their environment. But it's fair to say a lot of the action involves proteins, which do everything from catalyzing chemical reactions to providing structural scaffolding for various parts of the cell. All these different functions are dependent upon how the protein is organized in three dimensions, which occurs through a process called protein folding. All the dizzying variety of known proteins are generated by linking together a chain composed of 20 common amino acids (and a few rare variations on those). When you consider how quickly the number of possible combinations of these amino acids increases as the length of the protein does, however, it should be clear that the proteins that exist occupy only a small portion of the potential protein space. So, in this view, evolution has generated the rare, useful solutions within a sea of possibilities. But that's not the only way to look at things. The alternative view is that the backbone that links together the amino acids in a limited number of well defined structures, such as spirals called α-helixes and flat ribbons called β-sheets, and there are a relatively limited number of ways to link up these features into a structural feature that biologists call a fold. A new analysis of protein folds has now suggested that almost every existing fold fits into a network where it's possible to link any protein fold with any other through a series of seven or fewer steps, each of which goes through another, existing protein fold. The basic idea behind the paper is to use databases that contain the three-dimensional coordinates of all the atoms in every protein for which we know the structure. Using this data, researchers have identified a large collection of folds, which the authors define as "a particular spatial arrangement of α-helical and/or β-sheet secondary structures." That's where the new paper (and a hefty dose of computing power) comes in. The authors went through and compared every known fold with every other one in a pairwise fashion, calculating the degree to which the folds are related, using a measure called the "TM-score." (This paper seems to have more details on the alignment.) Because TM-scores have a known measure of statistical significance—the best alignment of two random proteins is 0.3, with a standard deviation of 0.01—the authors required a score of 0.4 before they'd consider two folds to be related. They then performed network analysis to create clusters of related folds. The surprise was that they got what's in essence a single, densely-packed cluster. Over 80 percent of the total fold-space was within four hops (where each hop brings you to another related fold) from the rest of the cluster. If you extend out to eight hops, you can incorporate over 98 percent of the known protein folds. This densely packed graph remained even after the authors had eliminated all the proteins that were known to be related via evolution. The authors argue that there's simply a limited number of ways to pack together a hydrogen bonded structure, and nature has explored more or less all of them. They support this argument by showing that they can see a similar network when they feed their system a set of structures generated from random, hydrogen-bonded peptides. So, what's it all mean? Well, in practical terms, if the authors are right, then the protein solving problem—the one that some of you may have been donating your spare CPU and GPU cycles to—may not be as difficult as some might have thought. If any potential arrangement is possible, then it's tough to see where an unfolded protein might wind up. But if we've really exhausted the biologically relevant fold space already, then the solution to the protein-folding problem would be severely constrained. In evolutionary terms, the authors suggest the results may support the "Big Bang theory of protein evolution," which suggests that early life was quickly able to explore most of the useful fold space, and has just been tinkering with variations on them since. I'm not entirely convinced it does. In many cases, only a few key amino acids form the hydrogen bonds and charge interactions that hold a fold together. It's easy to imagine that you only have to tweak a few of these to switch from a given fold to something that's closely related. But it's easy to imagine a lot of things; the authors haven't gone through and determined whether that's actually true in the cases that their approach has identified. It's not even clear that we currently have enough information to do this sort of comparison, given that we'd need to have some measure of all the amino acid combinations compatible with a given fold. Still, it's an intriguing idea, and one that fits in nicely with the growing recognition that emergent properties—situations where ensembles of something behave differently from individual instances—may play a significant role in dictating the behavior of natural systems. If this idea turns out to be right, it's possible that the diversity of protein structures we see arises simply from the properties of the amino acids they're comprised of. |
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Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
If possible just post only some lines and the link, like this many thanks
For the first time, researchers have experime...ternational AIDS Society. For the first time, researchers have experimentally induced antibodies that neutralize HIV-1 and simultaneously recognize both HIV-1 envelope protein and lipids. The results were reported by U.S. Military HIV Research Program (MHRP) researchers on Aug. 25 in the online version of AIDS, the official journal of the International AIDS Society. The lead investigators, Dr. Gary Matyas and Dr. Carl Alving, researchers in the Division of Retrovirology, MHRP, Walter Reed Army Institute of Research (WRAIR), and their collaborators, conducted the exploratory study using small synthetic HIV-1 peptides encapsulated in liposomes containing lipid A as an adjuvant... |
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Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
interesting approach aimed at dormant HIV reservoirs ¡¡¡
Researchers identify promising agents for HIV cure research ------------------------------------------------------------------------------ Researchers from the University of North Carolina and Merck are identifying promising new leads in the search for agents that may be able to purge HIV from resting CD4 cells, a key requirement for any prospect of a cure for HIV infection. The findings, reported by David Margolis and Nancie Archin in the September 15th edition of AIDS, show that a group of compounds called class 1 HDAC inhibitors show the most promise in activating previously latent HIV within resting CD4 cells. The findings may also explain why previous studies using another HDAC inhibitor, the antiepileptic valproic acid, showed only weak effect. After integration into the host genome HIV can remain silent within a resting CD4 cell for many years, provided that it is not stimulated into replication by signals that hit the long terminal repeat portion of the virus’s genetic code. Once stimulation occurs, a complex chain of events occurs within the cell that leads to HIV replication. http://aidsmap.com/en/news/11EDB38F-BC91-4EC1-AF1D-F83DB5316953.asp |
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Former Member
Cruncher Joined: May 22, 2018 Post Count: 0 Status: Offline |
This should be completed about now, I wonder when they will publish any results.
Phase III Trial in Thailand MHRP is in the follow-up stages in Thailand of the world's largest Phase III study of a complex HIV vaccine candidate. The trial enrolled 16,402 study participants at 50 health centers and hospitals in eight districts. An Independent Data Safety and Monitoring Board met in July 2007 to conduct an interim analysis of the trial in Thailand. The Board recommended that the study continue, because there were no safety concerns with the vaccine. While no firm conclusions can be drawn from this interim analysis for efficacy of the vaccine, predetermined benchmarks for statistical futility were not met. Study officials expect that the trial will continue until the final analysis, which is scheduled for the summer 2009. http://www.hivresearch.org/vaccine/index.html http://www.hivresearch.org/global-efforts/thailand.html |
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