Role of parametric resonance in virological failure during HIV treatment interruption therapy

We present a novel hypothesis that could explain virological failure to structured treatment interruptions (STI). We analysed a classic mathematical model of HIV within-host viral dynamics and found that non-linear parametric resonance occurs when STI are added to the model; resonance is observed as virological failure. We simulated clinical trial data and calculated patient-specific resonant spectra. We gained two important insights. First, within an STI trial, patients who begin with similar viral loads can be expected to show very different virological responses as a result of resonance. Second, and more importantly, virological failure is not simply due to STI or patients' characteristics; instead it is the result of complex interaction between STI and the patient's viral dynamics. Hence, our analyses show that no universal regimen with periodic interruptions will be effective for all patients.