In April 1995, Merck and the National Institute of Allergy and Infectious Diseases began recruiting patients for a trial examining the effects of a three drug combination of the protease inhibitor indinavir and two nucleoside analogs. illustrating the substantial benefit of combining 2 NRTIs with a new class of anti-retrovirals, protease inhibitors, namely indinavir. Later that year David Ho became an advocate of this "hit hard, hit early" approach with aggressive treatment with multiple antiretrovirals early in the course of the infection. Later reviews in the late 90s and early 2000s noted that this approach of "hit hard, hit early" ran significant risks of increasing side effects and development of multidrug resistance, and this approach was largely abandoned. The only consensus was on treating patients with advanced immunosuppression (CD4 counts less than 350/μL). Treatment with antiretrovirals was expensive at the time, ranging from $10,000 to $15,000 a year.