Resistance evolution in HIV - modeling when to intervene.

The treatment of HIV is complicated by the evolution of antiviral drug resistant virus and the limited availability of antigenically independent antiviral regimens. The consequences to the patient of successive virological failures is such that many strategies to minimize the occurrence of such failures are being investigated. In this paper, a Markov chain-based model of virological failure is introduced. This model considers sequential failure events, and differentiates between several modes of virological failure. This model is then used to evaluate the resistance- targeted interventions by means of testing the impact of a viral load preconditioning strategy on total treatment regimen longevity in HIV patients. It is shown that a proposed intervention targeting pre-existing resistance has the potential to increase the expected time to three sequential virological failures by an average of 3.3 years per patient. When combined with an intervention targeting patient compliance, the total potential increase in the time to three sequential virological failures is as high as 11.2 years. The impact on patient and public health is discussed.