Let's very pessimistically say this attack killed 50% of viruses, and only those lucky enough to have a mutation at the cleavage site managed to survive, and then multiply after, making the virus immune to that specific cleavage. Couldn't you then cleave at a few sites at once? With 64 different cleavage sites, only 1/2^64 viruses will survive, meaning it's pretty much completely certain you will kill every last viru…
From the article... > Both he and Liang think that the problem can be surmounted, for instance by inactivating several essential HIV genes at once...
I'm not positive this is right... but I would think a rough estimate on the upper bound could be arrived at assuming each mutation is equally likely and independent. Then the probability of a single mutation at any given site would follow a Poisson distribution with k=1 and r=.004:
r^k*exp(-r)/k! = r*exp(-r)= 0.00398
Then the probability of a mutation at n=2 sites in the same cell would be: (r*exp(-r))^n= 1.58 x 10^-5
If each infected cell infects N=10,000 new cells each generation g, after one generation (g=1) the expected number of cells containing a set of two specific mutations would be: N^g*(r*exp(-r))^n= 0.158
However after two generations there would be 10^8 infected cells and 1587 would be mutants at any two given sites. Then for any n=3 sites there would be about 6 cells containing mutations at each.As I said, that would definitely be an upper bound. Some sites will be less likely to mutate than others, eventually you run out of new cells, etc.
Also, this ignores that cutting the DNA may be killing the cells.
[1] http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1000906
[2] http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002251
[3] http://www.ncbi.nlm.nih.gov/nuccore/AF033819