Another possible (or at least I do not see why this can not be the case) approach to "reservoirs" (described application is cancer treatment):


Heating Nanoparticles to Kill Tumor Cells

ScienceDaily (Nov. 24, 2010) — Magnetic fluid hyperthermia (MFH) is a promising new cancer treatment that essentially "fries" cells inside tumors. The procedure has been used successfully in prostate, liver, and breast tumors. Magnetic nanoparticles (each billionths of a meter in size) are injected into the body intravenously and diffuse selectively into cancerous tissues. Add a high-frequency magnetic field, and the particles heat up, raising the temperature of the tumor cells.

"The entire tumor volume is heated above a threshold treatment temperature -- typically 42 degrees Celsius (107.6 degrees Fahrenheit) -- for generally 30 minutes," explains engineering graduate student Monrudee Liangruksa of Virginia Tech.

The outcome? As described November 23 at the American Physical Society Division of Fluid Dynamics (DFD) meeting in Long Beach, CA, when the nanoparticles are heated, cancer cells die with no adverse effects to the surrounding healthy tissue.

To further perfect the technique, Liangruksa and her colleagues explored the effects of different types of magnetic nanoparticles. The most promising varieties, they found, were iron-platinum, magnetite, and maghemite, all of which generate therapeutically useful heating. "However, we wish to use MFH in humans," she says, and "the most biocompatible agents are magnetite and maghemite. Iron-platinum is toxic and vulnerable to oxidation."

American Institute of Physics (2010, November 24). Heating nanoparticles to kill tumor cells. ScienceDaily. Retrieved June 6, 2011, from http://www.sciencedaily.com­ /releases/2010/11/101123191306.htm

http://www.medicalnewstoday.com/releases/227726.php

"Article Date: 07 Jun 2011

Unique Clinical Trial Addresses Important Questions About Treating Cancer In Those With HIV

As the world marks the 30-year anniversary of the first reporting of HIV/AIDS, now comes the realization of a new challenge for people with the incurable disease. For reasons not yet clear, people with HIV face a higher rate of cancers not usually associated with HIV. This increasing rate of "non-AIDS defining cancers" includes lung, head and neck, liver, kidney, and anal cancers, among others. The alarming uptick in cancer rates highlights the critical need to understand how to treat tumors in people taking highly active anti-retroviral therapy (HAART) for HIV. Given what is known about HAART drug interactions, can newer targeted cancer therapies be given safely to patients with HIV?..."

Dan60, thanks for the link!
SekeRob, thanks, point taken. You are absolutely right, these particular articles are not related to the topic. Although the presented approach looks valid for HIV also. First article confirms that antivirals can be delivered across the blood/brain barrier (and as far as I can remember last year research confirmed HIV presence in the brain). Second article is about application of physical laws in medical domain which to me is also a new field of research, and in practice meaning that if there is a way to identify a latent cell (let's suppose a flag-protein), then it can be targeted with a complex of binding mechanism + nanoparticle. After that the same heating mechanism can be applied, destroying the cell and the virus since the temperature used for cancer is above HIV threshold.

Question: I can not find any studies on when HIV enters latency. Are you aware of any? If so, can you share a link? Does it happens after the infection or only when HAART is started? The point in asking is to understand is it a logical protection mechanism of the virus (absence of free-floating virus achieved by antivirals pushes HIV to go into the latency stage, change in infected person temperature, or even presence of the antibodies) or is it the virus unlogical nature that sometimes just "prefers" latency to multiplication opportunity? Will the presence of the virus in blood (or something mimicking the virus) bring it back to its active lifecycle?

http://online.wsj.com/article/SB10001424052702303936704576397491582757396.html

Scientists using a powerful mathematical tool previously applied to the stock market have identified an Achilles heel in HIV that could be a prime target for AIDS vaccines or drugs. [...] To find the vulnerable sectors in HIV, Drs. Chakraborty and Dahirel reached back to a statistical method called random matrix theory [...] to sift through most of HIV's genetic code for correlated mutations, without reference to previously known functions or structures of HIV. The segment that could tolerate the fewest multiple mutations was dubbed sector 3 on an HIV protein known as Gag. [...] the capsid, or internal shell, of the virus has a honeycomb structure. Part of sector 3, it turns out, helps form the edges of the honeycomb. If the honeycomb suffered too many mutations, it wouldn't interlock, and the capsid would collapse.

For years, Dr. Walker had studied rare patients, about one in 300, who control HIV without taking drugs. He went back to see what part of the virus these "elite controllers" were attacking with their main immune-system assault. The most common target was sector 3. Dr. Walker's team found that even immune systems that fail to control HIV often attack sector 3, but they tend to devote only a fraction of their resources against it, while wasting their main assault on parts of the virus that easily mutate to evade the attack. That suggested what the study's authors consider the paper's most important hypothesis: A vaccine shouldn't elicit a scattershot attack, but surgical strikes against sector 3 and similarly low-mutating regions of HIV. [...]

It seems that a new anti-HIV drug has very recently been released called Edurant (rilpivirine) . I am noting it here as the appended article mentions that it seems to be especially effective against drug resistant HIV, and finding new treatments for drug resistant HIV is a the main objective of Fight against Aids at Home World Community Grid project. From what I was able to find out about it on the internet this new anti-HIV drug appears to be a non-nucleoside reverse transcriptase inhibitor (NNRTI).

http://www.bio-medicine.org/biology-news-1/Ru...y-news+%28Biology+News%29


"Date:6/23/2011

Rutgers laboratory helped to create new HIV drug

Two decades after a Rutgers team began working with legendary drug developer Paul Janssen, founder of a Belgian subsidiary of pharmaceutical giant Johnson & Johnson in an effort to create new and potent drugs to fight AIDS, the U.S. Food and Drug Administration has approved the second anti-HIV drug that came from this collaboration.

"For a drug to successfully make it to the finish line, countless obstacles must be overcome," said Eddy Arnold, Board of Governors Professor of Chemistry and Chemical Biology, and a resident faculty member of the Center for Advanced Biotechnology and Medicine who led the Rutgers team. "As a researcher in biomedical sciences I can tell you that helping to create new medicines is something you always dream about."

The newest AIDS drug, (rilpivirine) Edurant the first to be approved by the FDA in the last three years and manufactured by Tibotec Therapeutics, a subsidiary of J&J was developed in 2001 and took a decade to make its way through the regulatory process and clinical trials.

"From the beginning, we knew this would be a long-term project," said Arnold whose research group team received $20 million mostly from the National Institutes of Health as well as two prestigious MERIT (Method to Extend Research in Time) NIH awards, an honor bestowed on less than 5 percent of NIH grant recipients. "Many challenges have been faced and overall it has been more like a marathon than anything else."

Resistant strains of HIV are a growing medical problem because the virus is constantly mutating, and the changes can cause existing AIDS drugs from being able to work. Arnold's team developed innovative models that explain not only why Edurant, approved by the FDA last month, and Intelence, approved in 2008, are particularly effective against drug-resistant viruses but can also be used in the development of treatments for a wide variety of other diseases. The gist of the model is that flexibility of a drug can allow it to adapt to changes in HIV.

Clinical trials for Edurant, which included more than 1,300 adults with HIV, indicated that 83 percent of those who were given this anti-AIDS drug for a 48-week period had undetected levels of HIV in their blood at the conclusion of the clinical trial. The new drug can be prescribed as a once-a-day pill to HIV-positive adults who have not received any prior treatment or therapy. Besides being available in the United States, a generic form of the drug will be made available to millions of people in Saharan Africa, India and other developing nations.

"Development of this newest AIDS drug represents a wonderful example of the biomedical power that can be harnessed by scientific collaborations and partnerships between university, government, and private sector research enterprises," said Kenneth J. Breslauer, dean of Life and Health Sciences. "No more satisfying and important outcome can result from university research."

This scientific collaboration began in 1987 when the Rutgers team entered into a partnership with Stephen Hughes, an AIDS researcher at the National Cancer Institute. Both were interested in understanding the molecular structure and function of reverse transcriptase, an essential part of the AIDS virus, not only for its fundamental significance, but also because they believed it would provide guidance for the design of more effective drugs.

Three years later, Arnold reached out to Janssen at the J&J subsidiary, Janssen Pharmaceutica, which had developed promising compounds to prevent reverse transcriptase from being able to create a genetic copy of the AIDS virus. The Rutgers team suggested that crystal structures of the compound created by Janssen, bound to the reverse transcriptase enzyme, could help the company understand and improve its chemical structures and be used to develop more effective AIDS drugs.

They worked together for the next 13 years, during which time Janssen provided $2 million to help fund the Rutgers team's research efforts to develop drugs that would be effective against drug-resistant mutants of the AIDS virus. A pivotal breakthrough happened in 1998 when dapavirine -- which works by preventing HIV from replicating its genetic material after the virus enters a healthy cell was developed. Further refinements of the drug led to creation of two anti-AIDS drugs: Intelence approved by the FDA in 2008, and Edurant, which came on the market in May and has shown exceptional potency against drug resistant HIV."