SL Accounting for non-compliance is certainly one. Another area is the understanding of how the virus works and therefore of strategies of how to fight it. This area changed 180 degrees about two years ago when a whole new model was developed for what goes on inside the body of an infected person. Using some mathematical models, actually very simple deterministic differential equations models, investigators were able to show that what appears to go on is a huge daily battle where hundreds of millions of virions are being neutralized by the body's immune cells and what happens over a period of years is that the body just can't keep producing enough. Much more work has to be done in this area because what has been done so far is largely deterministic and it does not account for heterogeneity.
Stochastic models are what is being called for here.
The other big issue now is that you can get treatments that keep the virus suppressed almost at undetectable levels for prolong periods of time, but not forever because resistance does eventually happen. We can't do a clinical trial to answer these questions because it will take too many years to get results and by then our knowledge of the treatment of the disease will have changed. So now there are stochastic models being developed for the whole disease process to try to answer these questions. I see this as a challenging area where we will see important developments in the next few years. SLs CBAR is the Center for Biostatistics and AIDS Research.