Stopping antiretroviral therapy.

Combination antiretroviral regimens continue to fail in some patients [1,2]. Here we consider a factor that may be important; i.e. how patients stop therapy. We previously postulated that if one drug in a regimen has a significantly longer half-life than others, and all agents are stopped simultaneously [3] then the patient will be taking essentially ‘functional monotherapy’ after the shorter half-life drugs are eliminated (Fig. 1a). The probability of resistance emerging will depend on: (i) the drug’s genetic barrier; (ii) the magnitude of viral replication when the drug remains at a concentration capable of inducing resistance; and (iii) the length of time the drug remains in the zone of resistance selection.