AVANTI 3: a randomized, double-blind trial to compare the efficacy and safety of lamivudine plus zidovudine versus lamivudine plus zidovudine plus nelfinavir in HIV-1-infected antiretroviral-naive patients

The objective of our randomized, multicentre, double-blind, placebo-control led study was to investigate the safety, tolerability, and antiretroviral a nd immunological effect of double and triple combination therapy regimens. A total of 105 antiretroviral therapy-naive patients were randomized to rec eive either zidovudine (300 mg twice per day) plus lamivudine (150 mg twice per day) plus nelfinavir placebo (three times per day) (n=52), or zidovudi ne/lamivudine (dose as before) plus nelfinavir (750 mg three times per day) (n=53) for 28 weeks. After this time, patients were allowed to switch to o pen-label zidovudine/lamivudine/nelfinavir. The overall log,, reduction fro m baseline in plasma HIV-1 RNA was significantly greater in the zidovudine/ lamivudine/nelfinavir group than the zidovudine/lamivudine group (P=0.001; median treatment difference, -1.01 log(10) copies/ml; 95% confidence interv al -1.23 to -0.79), as measured by the average area under the curve minus b aseline over 28 weeks. Increases from baseline in CD4 cell counts were stat istically significantly greater in the zidovudine/lamivudine/nelfinavir gro up (101.5 cells/ml) than the zidovudine/lamivudine group (47.0 cells/ml; P= 0.027) at week 28. Of note, the addition of nelfinavir from weeks 28-52 led to an increase in the proportion of subjects with plasma HIV-1 RNA <400 copies/ml from 17% (9 /52 patients on zidovudine/lamivudine) to 50% (13/26 patients who switched to zidovudine/lamivudine/nelfinavir). Incidence of drug-related adverse eve nts was similar in the two groups, except for nausea (more common in zidovu dine/lamivudine group; 40 versus 17%) and diarrhoea (more common in zidovud ine/lamivudine/nelfinavir group; 45 versus 14%). In conclusion, our study c onfirms the efficacy of triple combination therapy with two nucleoside anal ogues and a protease inhibitor compared with double-nucleoside therapy. Int erestingly, the addition of nelfinavir to zidovudine/lamivudine, even after 6 months of double nucleoside therapy, led to a substantial virological be nefit that was sustained over 24 weeks in a subset of patients.