Balancing immunological benefits and cardiovascular risks of antiretroviral therapy: when is immediate treatment optimal?

We developed a mathematical model to identify the timing of antiretroviral therapy (ART) initiation that optimizes patient outcomes as a function of patient CD4 count, age, cardiac mortality risk, sex, and personal preferences. Our goal was to find the conditions that maximize patient quality-adjusted life expectancy (QALE) in the context of our model. Under the assumption that ART confers disease progression and mortality benefits at any CD4 count, immediate treatment initiation yields the greatest remaining QALE for young patients under most circumstances. The timing of ART initiation depends on the magnitude of benefit from ART at high CD4 counts, the magnitude of increases in cardiac risk, and patients' preferences. If ART reduces HIV progression at high CD4 counts, immediate ART is preferable for most newly infected individuals <35 years even if ART doubles age- and sex-specific cardiac risk.