NFV is a novel and potent MV protease inhibitor that was studied in a randomized double-blind placebo-controlled protocol (#511) in 297 HIV infected patients that began in February, 1996. All patients received AZT + 3TC and either NFV placebo or NFV at 500mg TID or 750mg TID with food. This study enrolled antiretroviral naive patients who had viral loads of greater than 15,000 copies/ mL. There was no CD4 cells count entry criterion. Mean baseline viral load was 4.9 log10 copies/mL and the mean CD4 cell count was 283 cells/mm3 (range 0- 766). At 24 weeks, mean viral load reduction for the 750mg dose was 1.99 log 10 copies/mL with a mean rise of CD4 cells of 155 cells/mm3. At 52 weeks mean viral load reduction was sustained and CD4 cells continued to increase from baseline. The percentage of patients with plasma HIV RNA below 500 copies/mL has been maintained at approximately 80%. The duration cf response was statistically significant for both of the NFV arms compared to control. Median time to failure, defined as the return to baseline of either CD4 cells or HIV RNA, for the control group was 51 days, neither of the NFV arms have reached the median point Influence of baseline viral load and baseline CD4 will be discussed. NFV continues to demonstrate an excellent safety profile in combination with AZT and 3TC; the major NFV-related toxicity remains loose stool/diarrhea. This side effect may diminish with time and is controllable with over-the-counter antidiarrheal medication. Although NFV inhibits CYP3A, it is unlikely to inhibit other P450 isoforms; thus most commonly used concomitant HIV medications may be administered with NFV.