My colleagues and I had been working for a number of years to develop a novel therapeutic inhibitor of the HIV-1 protease enzyme. Eventually, a specific and potent inhibitor, indinavir, was developed and brought into Phase I trials in patients persistently infected with the virus. While sitting at home on a dreary, cold winter night in early 1994, I was staring at the figure that depicted the patient's plasma virus levels while on treatment. I was depressed by the observation that most patients exhibited only a modest and transient drop in virus levels. Yet, one patient in particular (blue diamonds), presented a profound and sustained antiviral effect. I recall the sense of excitement as I arrived at the belated realization that, if such an effect were possible in one patient, then it should be possible in all if we could design a sufficiently potent therapeutic regimen. This led to the design of the first potent "triple therapy" regimens that allowed for long-term treatment and control of HIV-1 disease.[1]