Varying efficacy of HIV drug cocktails explained

best to quote one of the comments posted:
Either this article doesn't explain enough details about the relationships, or i just don't understand what they're talking about. Either is possible. Can some other reader shed some extra light on the topic please? Can I get an equation or something? Any help would be nice. jim.brookhyser

Increasing dose works at critical times in virus’s life cycle

By Rachel Ehrenberg

Web edition : Wednesday, July 13th, 2011

A new mathematical model of HIV-fighting drugs reveals the biology beneath the varying success of such treatments. Infection with HIV was a death sentence until the introduction of multidrug cocktails, yet the differential effectiveness of the combinations has remained a puzzle. The research, published July 13 inScience Translational Medicine, could help refine therapies for HIV and other viruses such as hepatitis C.
Slightly boosting the dose of some HIV drugs has a profound effect if those drugs are attacking multiple targets, the new model reveals. Finding that more bullets can kill more targets may seem obvious, says AIDS researcher and Howard Hughes Medical Institute investigator Robert Siliciano of Johns Hopkins University. But the realization required a shift in thinking about a very old idea: the relationship between a drug’s dose and its effect.
For centuries, drug effectiveness has been visualized with what’s called the dose-response curve. This relationship often takes on a stretched-out “S” shape when graphed.
But in 2008, Siliciano’s then graduate student Lin Shen realized that the steepness of the incline of the “S” — its slope — varied with different classes of HIV drugs. A gradual climb meant that increases in drug concentration gradually improved the response. But a very steep slope meant that tiny increases in a drug’s concentration could wipe out significantly more target molecules.

Detailed 3D Model of HIV Unveiled

Recently, Visual Science Company, led by Ivan Konstantinov, created the most detailed and accurate 3D model of the HIV virus to date.

The model includes 17 viral and cellular proteins and 160,000 lipid molecules of 8 different types, with all components in proportion with a real HIV particle.  The orange structure depicts the actual genome and the gray matter represents the parts of the virus acquired when contact is made with a human cell.

Images were created in approximately 3 months, based on data available in over 100 leading science journals and publications.

“This is one of many supramolecular structures already designed,” notes Ivan Konstantinov, the lead development engineer.  “In February 2010, we launched a project aimed at creating molecular models of the most well-known human viruses. In addition to the HIV model, we’ve designed the swine flu virus (A/H1N1) and the adenovirus model.  We specifically elected the HIV virus, as it’s a well studied object, allowing us to depict its different parts from envelope proteins to genome fragments.”

“My team considers such 3D models as a new way to present and promote scientific data about ubiquitous human viruses. We attempt to show viral particles as close to the real version as possible, offering the scientific community and general public - a better understanding of the complexity of these structures,” adds Konstantinov.

Ongoing work similar to Konstntinov’s, not only increases understanding and knowledge, but also provides additional fuel for researchers striving to find a cure for HIV-AIDS.