Motivated by the inability of current drug treatment to provide long-t
erm. benefit to HIV-infected individuals, we derive HIV therapeutic st
rategies by formulating and analyzing a mathematical control problem.
The model tracks the dynamics of uninfected and infected CD4(+) cells
and free plasma virus, and allows the virus to mutate into various str
ains. At each point in time, several different therapeutic options are
available, where each option corresponds to a combination of reverse
transcriptase inhibitors. The controller observes the individual's cur
rent status and chooses among the therapeutic options in a dynamic fas
hion in order to minimize the total viral load. Our initial numerical
results suggest that dynamic therapies have the potential to significa
ntly outperform the static protocols that are currently in use; by ant
icipating and responding to the disease progression, the dynamic strat
egy reduces the total free virus, increases the uninfected CD4(+) coun
t, and delays the emergence of drug-resistant strains. (C) 1997 Academ
ic Press Limited.