Science News - August 13, 2011

“HiV is a replicating machine.” — STEVEN DEEKS
Why some HIV
cocktails pack
a bigger punch

By Rachel Ehrenberg

A new mathematical analysis of HIV-fighting drugs may reveal why some combinations work better than others.

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 in the July 13 Science 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 mathematical 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 the last century, drug effectiveness
has been visualized with what’s called
the dose-response curve. This relation-
ship often takes on a stretched-out “S”
shape when graphed.

Percent of targets killed

20 Halting HIV For two hypothetical HiV drugs, the dose that kills half the target cells (dotted line) is defined as 1. The steep slope of the red drug indicates that for it, a small increase in dose has a big effect on response. Drugs that effectively attack HiV at certain points in the virus’s life cycle have these steep slopes.