Optimal drug treatment regimens for HIV depend on adherence

Drug therapies aimed at suppressing the human immunodeficiency virus (HIV) are highly effective, often reducing the viral load to below the limits of detection for years. Adherence to such antiviral regimens, however, is typically far from ideal. We have previously developed a model that predicts optimal treatment regimens by weighing drug toxicity against CD4+ T-cell counts, including the probability that drug resistance will emerge. We use this model to investigate the influence of adherence on therapy benefit. For a drug with a given half-life, we compare the effects of varying the dose amount and dose interval for different rates of adherence, and compute the optimal dose regimen for adherence between 65% and 95%. Our results suggest that for optimal treatment benefit, drug regimens should be adjusted for poor adherence, usually by increasing the dose amount and leaving the dose interval fixed. We also find that the benefit of therapy can be surprisingly robust to poor adherence, as long as the dose interval and dose amount are chosen accordingly.