Drug-sparing regimens for HIV combination therapy: benefits predicted for "drug coasting"

Structured Treatment Interruptions (STI) during HIV drug therapy were thought to potentially reduce side effects and toxicity, boost immune involvement, and possibly lower the viral set-point. Clinical trials of STI regimens, however, have had mixed results. We use an established mathematical model of HAART to estimate possible therapeutic outcomes for STI and for other, similar patterns in HIV combination therapy. We perform an exhaustive search of patterns of up to 60 days, for triple-drug combinations involving accurate pharmacokinetics for 12 specific antiviral drugs. The results of this analysis are consistent with recent clinical trials which have demonstrated that STI-type patterns, involving therapy interruption of weeks or months, are rarely optimal. Our analysis predicts, however, that the benefit of treatment can often be improved by including very short drug-free periods, during which the patient effectively "coasts" for a day or two on adequate drug concentrations due to the long half-life of some pharmaceuticals. Our analysis predicts many cases in which this may be achieved without increasing the risk of drug-resistance. This suggests that "drug coasting" patterns, significantly shorter than STI patterns, may merit further clinical investigation in efforts to find drug-sparing regimens for HIV.