Bryologs help find hidden HIV reservoirs
One of the obstacles that HAART drug cocktails for HIV have not been able to overcome totally is the persistence of viral reservoirs hidden within T-cells and other areas of the body.
These reservoirs can erupt, replicate, and repopulate the whole body making drug control of AIDS very difficult.
Laboratories are working with a small marine organism bryozoan named Bugula neritina which produces a potent protein kinase C-activating compound.
While the natural compound is difficult to produce and has limiting side effects, scientists are developing synthetic analogues called bryologs for increased production and health safety.
In certain cell lines, the resulting synthetic bryologs are up to 1000 times more potent and show no toxic effects at this time (DeChristopher B et al, Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro, Nature Chemistry, July, 2012).
New HIV transmission mathematical model
The March 2012 Reed College magazine describes the work of Martina Morris at the University of Washington Center for Studies in Demography and Ecology.
She has worked to develop a model of STD viral transmission speed based on concurrency or people having more than one partner at a time.
This social situation was presented to her during her work in Uganda, one of the African countries with a rapid spread of AIDS.
Her model confirms how an apparently small increase in concurrency can speed up viral transmission dramatically, especially when compared to serial monogamy transmission.
You can view an animated video of this model showing the infection rate at http://statnet.org/movies
HIV spreads by hijacking the body's proteins
Researchers at the University of California San Francisco, and Gladstone Institutes have identified a group of human proteins called restriction factors that originally evolved to block viruses such as HIV and are now hijacked by HIV.
By using systematic analysis of approximately 500 interactions between human proteins and proteins produced by HIV, the scientists discovered a restriction factor called APOBEC3G. This factor normally prevents the virus from reaching the CD4 T white blood cells that are a major component of the immune system and defense against HIV.
However, when an HIV protein binds to the human protein, the HIV becomes stronger and the human restriction factor APOBEC3G degrades and becomes less effective. Then the virus is free to infect the CD4 immune cells and spread throughout the body.
Researchers hope this kind of analysis will help identify biochemical targets for new drug development.
This research is ongoing and preliminary. (Stefanie Jäger, Peter Cimermancic, Nevan J. Krogan, et al. Global landscape of HIV–human protein complexes. Nature, December, 2011)
TRIM5a protein and HIV
Researchers at Loyola University Department of Microbiology and Immunology are studying a protein that can destroy HIV in monkeys.
This protein, called TRIM5a, also occurs in humans but the human version is ineffective against HIV.
Dr. Edward Campbell leads a team of researchers working to identify the differences between the TRIM5a protein of monkeys and humans.
Using fluorescent proteins and a $225,000 microscope, they are searching among the 500 amino acids of this protein for specific areas that influence viral inhibition and destruction. They have already identified six individual amino acids that can lose the capacity to block HIV-1 infections in cell lines when altered.
They hope that further research can locate the specific amino acids effective in destroying the virus in order to develop theraputic agents.
This research is ongoing and preliminary.
HIV News: New Green Tea HIV Study
It has already been shown that EGCG (epigallocatechin gallate), the primary polyphenol antioxidant from green tea, can block attachment of HIV-1 to T cells. It stops HIV at the specific site on the CD4 molecule of the T cell walls that is used by HIV to enter the T cell and destroy it.
Now a new study takes that preliminary HIV prevention research further.
Texas researchers have found that EGCG prevented both HIV-1 isolates and four subtypes of HIV from binding to the CD4 molecule of T cells. They also found that EGCG protected macrophages from HIV.
EGCG inhibited the HIV infection in a dose-dependent manner: the more EGCG, the greater the protection. At EGCG levels (comparable to drinking green tea) that are tolerable to humans, the protection was statistically significant.
The researchers found no evidence of cell damage. They concluded that the primary mechanism of HIV prevention was the blocking action which prevented HIV from entering the T cells. They also found that only catechins like EGCG with galloyl and/or pyrogallol side groups provided this protection. Other catechins without those chemicals were not effective (Nance CL, Preclinical development of the green tea catechin, epigallocatechin gallate, as an HIV-1 therapy, Journal Allergy and Clinical Immunology, February 2009).
This is a preliminary cell study and has not been tested in vivo.
HIV News: Daily Meditation Helps HIV/AIDS
A new study tested 48 HIV-positive adults in a mindfulness meditation stress reduction program.
The program consisted of eight weekly sessions of two hours, one day-long retreat, and daily home practice. A control group had a single one day stress reduction seminar.
The mindfulness meditation stress reduction sessions concentrated on awareness of the present while not worrying about the past or future.
The meditation program participants kept their CD4+ T lymphocytes steady, a measure of the health of their immune systems. The control group showed a decline in their CD4+ T lymphocytes.
The differences were significant. The results were independent of anti-retroviral medication usage.
While this study is preliminary, researchers said that the daily meditation program not only supported the immune system, but also improved other quality of life measurements (Creswell JD, Mindfulness meditation training effects on CD4+ T lymphocytes in HIV-1 infected adults: A small randomized controlled trial, Brain, Behavior, and Immunity, July 2008).
The mindfulness meditation program is low cost and works in a group setting.
HIV News: Drug Resistant HIV
A common problem with disease therapies is drug resistance. Over time, mutations occur that stop the effectiveness of drug therapies, leading to treatment failure.
With HIV, general tests are available in developed countries that identify viral mutations and are used to help select primary and secondary lines of therapy.
A new study examined whether more sensitive testing for drug resistant HIV could reduce treatment failures.
Researchers examined 316 samples from 1400 HIV patients who had started therapy which included efavirenz. Initial testing did not show drug resistance.
95 patients experienced treatment failure. Of these 95, 7 showed drug resistance to efavirenz with more sensitive testing.
Of the 211 people who did not experience treatment failure, only 2 showed drug resistance to efavirenz with more sensitive testing (Johnson J, Minority HIV-1 Drug Resistance Mutations Are Present In Antiretroviral Treatment-Naive Populations And Associate With Reduced Treatment Efficacy, PLoS, July 2008).
While this research opens new doors for success in HIV therapy, it is still considered preliminary.
Read about green tea and HIV research here
HIV News: Living Longer With HIV
Life expectancy for people infected with HIV has increased 13.8 years in patients taking the improved combination antiretroviral therapy (cART) or the "drug cocktail."
A new study from the University of Alabama in the United States and Simon Fraser Unviersity in Vancouver, Canada tracked mortality among 43,355 HIV patients in Europe and North America. They found life expectancy increased from 36.1 years in people who began taking antiretroviral therapy in 1996-1999 to 49.9 years in people who began antiretroviral therapy in 2003-2005 (Mugavero M, Lancet, July 2008).
Regardless of this dramatic improvement, people who are HIV-positive have a life expectancy 20 years less than other people, including those with other chronic illnesses.
HIV News: Women And AIDS
As of 2007, 62% of all people living with HIV are women or adolescent girls, according to the United Nations.
Many social habits have promoted this high rate of infection, including:
These factors have led to a dramatic increase in female HIV infections, not only in Africa, but also Latin America, Asia, and Eastern Europe. In the United States, AIDS is the leading cause of death for African-American women age 25-34.
Global efforts include women's education, economic choices, and equal access to treatment.
Without this action, the infection rates will only get worse.
HIV News: HIV-1 Therapy With Most Effective Drugs
Researchers have now tracked the effectiveness of 757 three different HIV drug programs in 757 patients for a median of 112 weeks.
The most effective treatment was with efavirenz plus two nucleoside reverse-transcriptase inhibitors.
This three drug program achieved and maintained viral control longer than the other two treatment combinations: lopinavir-ritonavir plus two nucleoside reverse-transcriptase inhibitors, or lopinavir-ritonavir plus efavirenz only.
At the 96 week testing, 89% of the efavirenz group had fewer than 50 copies of plasma HIV-1 RNA per milliliter, compared to 83% in the lopinavir-ritonavir plus efavirenz only group and 77% in the lopinavir-ritonavir group.
Patients in the lopinavir-ritonavir group, also called the NRTI-sparing group (patients were not given any nucleoside reverse-transcriptase inhibitors), were most likely to show antiretroviral resistance mutations or HIV drug resistance.
While nucleoside reverse-transcriptase inhibitors can be more likely to have toxic side effects, in this study, all three groups maintained drug therapy without significant differences (Riddler SA, Class-sparing regimens for initial treatment of HIV-1 infection, New England Journal of Medicine, May 2008).
All three HIV treatment programs improved the patient's immune response.
Here's more HIV research.
HIV News: What Can Mathematics Do For You?
Fighting infections with drugs becomes more difficult as infective agents, bacteria and viruses, become inevitably drug-resistant.
Researchers have in the last few decades developed "drug cocktails" or mixtures to help prevent drug-resistance and continue to have effective treatments of infections. Some of the drug cocktails have been very beneficial for HIV/AIDS patients.
But deciding which drug to use, how many to use, what combination to use, and the amount of each one to use is a formidable job. For example, if only ten drugs were put together in six combinations, there would be approximately a million combinations to test for effectiveness.
Now with the help a new mathematical algorithm using a closed-loop optimization modality, researchers from UCLA, California, have been able to identify effective drug combinations rapidly.
Instead of going through a million combinations, they have identified effective drug cocktails in less than 30 repetitions.
In addition, they have found that these combinations can be effective with 90% reduced dosage (Wong PK, Closed-loop control of cellular functions using combinatory drugs guided by a stochastic search algorithm, Proceedings National Academy Sciences, April 2008).
Scientists hope that this mathematical technique will increase effective treatments for individual patients by completely customizing using drugs for diseases.
HIV News: HIV Persists In Gut
HIV can persist for years in viral reservoirs of lymphatic tissue throughout the body.
One rich viral reservoir area of lymphatic tissue is throughout the intestines, called gut-associated lymphatic tissue or GALT. HIV in the gut has been a strong contributor to the life-threatening damage from AIDS.
In a small study, scientists intensively tracked HIV-positive individuals using current antiretroviral drugs for almost 10 years.
While blood tests showed that their HIV was undetectable, more sensitive tests showed that HIV was persistently replicating throughout the gut lymphatic tissue.
The scientists concluded that eliminating HIV from these lymphatic viral reservoirs will need stronger drugs and more research (Chun TW, Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy, Journal of Infectious Diseases, February 2008).
Here's more HIV research.
HIV News: Copper Stops HIV
An inexpensive copper filter has stopped HIV-1 transmission.
People worldwide acquire HIV/AIDS not only through sexual transmission, but also through blood transfusions and breast feeding.
Up to 50% of the 700,000 cases of mother-child transmissions were attributed to breast feeding in 2001, and between 80,000 and 160,000 new HIV infections annually were attributed to blood transfusions (WHO). Infected blood transfusions are still responsible for 5% to 10% of new HIV infections in developing countries.
Now researchers have developed copper filtration which could be used to filter breast milk and blood transfusions. These copper filters have deactivated all HIV-1 isolates tested.
Both copper oxide powder filters and copper oxide-impregnated fiber filters were tested.
Both cell-free and cell-associated HIV-1 titers were inhibited in a dose dependent manner without cytotoxicity with both filters. For both filters, HIV virus deactivation included all 12 wild-type, drug-resistant laboratory or clinical types, as well as macrophage and T-cell trophic, and clade A, B, or C isolates in a non-strain-specific manner (Borkow G, Deactivation of human immunodeficiency virus type 1 in medium by copper oxide-containing filters, Antimicrobial Agents and Chemotherapy, February 2008).
If this new cost-effective technology can be successfully applied, it could reduce non-sexual HIV-1 transmission throughout the world.
Here's more research about HIV prevention.
Previous research has shown that interferon IFN can use proteins to cause the retention of encapsulated viruses at the cell wall and prevent them from budding off into the blood stream to infect other cells. Those proteins "tether" the virus like sticky Velcro.
This process was shown to almost completely block HIV replication in HIV strains lacking a protein called Vpu. This process also protected against Ebola viral release from the cell wall. Unfortunately, when Vpu was expressed, both HIV and Ebola could effectively release viral particles, and infect new cells (Neil SJ, Cell Host and Microbe, 2007).
Now, researchers have identified the Velcro-like protein they call "tetherin." Tetherin works as long as the virus does not have Vpu, but even Vpu-deficient viruses can escape the cell wall when tetherin is missing (Neil SJ, Nature, 2008).
These discoveries will hopefully open up new areas for viral research and theraputic targets.
Here's more HIV prevention research.
HIV News: Another Piece Of The Puzzle
Researchers from the University of Zurich, Switzerland, and the University of Washington, U. S. have reverse engineered a peptide protein that may be able to interfere with HIV replication.
One step in HIV reproduction involves the movement of HIV viral RNA out of the nucleus of the infected cell into the cytoplasm for discharge into the host's body, thus spreading the disease. This transport is facilitated by other viral proteins called Rev units.
Rev units attach to certain sites on the HIV viral RNA called Rev-responsive elements (RRE). If a chemical could prevent the Rev unit attachment to the RRE, then transport out of the nucleus could be stopped, and the spread of HIV throughout the body could be slowed or even stopped.
After many screening steps, the researchers created a hairpin shaped peptide that mimics the Rev units, is recognized by the HIV RNA, binds to the RRE, and displaces the original Rev unit (Robinson J, Angewandte Chemie, 2007). This could potentially block the active Rev units, substituting inert units, and thus stopping the transport of HIV to the rest of the body.
Another area of HIV research involves blocking the entry of HIV into new cells.
HIV News: Tuberculosis Added To HIV Pandemic
Approximately 14 million of the 40 million people with HIV/AIDS also have multi-drug resistant (MDR) tuberculosis or extreme drug resistant (XDR) tuberculosis.
In sub-Saharan Africa, half of all new HIV/AIDS patients are co-infected with TB.
Some areas in South Africa have seen drug resistant tuberculosis increase by 600% just between 1996 and 2004.
Along with malaria transmitted by mosquitoes (vectors), tuberculosis transmitted through the air and HIV transmitted through sexual and blood/needle contact, are the three most deadly contagious diseases for humanity in our time.
HAART, or the drug combination known as Highly Active Anti-Retroviral Therapy, is used widely for HIV patients.
Now a new study shows that HAART also reduces brain damage from HIV.
Researchers tested 53 HIV-positive men and women for neurofilament light protein in their cerebrospinal fluid, a biomarker for brain damage. Twenty-one showed high levels.
There were improvements after only three months on HAART. After one year of treatment, 17 of the 21 showing high levels of neurofilament light protein were down to normal levels (Mellgren A, Neurology, 2007).
When the HIV infection damages the brain, it can also cause AIDS-related dementia which complicates the care of the patient.
A new study at UCLA found that HIV patients who tested highest for chaotic or unpredictable daily lives also received reduced HIV treatment.
The high scoring HIV positive patients tended to lack spouses or partners, or basic needs like transportation or housing (Wong M, Journal General Internal Medicine, 2007).
The long term effect of reduced or interrupted HIV treatment programs is not yet determined.
HIV/AIDS is one of the greatest pandemics the world has known, with over 40 million people currently infected and approximately 25 million deaths since 1981 (Avert.org).
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