November 19, 1999
Because most initial studies of protease inhibitors combined the PI with ZDV and 3TC, there are scant data regarding the activity of PIs when used in combination with other nucleoside RT inhibitors (NRTI). This randomized trial compared the activity of ZDV/3TC/IDV with that of d4T/ddI/IDV in 3TC- and PI-naive patients who had <4 weeks prior treatment, CD4 counts $200/mL and plasma HIV-1 RNA >10,000 copies/mL. The primary endpoint was the proportion of patients with plasma HIV-1 RNA levels <500 copies/mL.
Fifty-three percent of patients in the d4T/ddI/IDV arm and 45% of patients in the ZDV/3TC/IDV arm had plasma HIV-1 RNA levels <500 copies/mL at weeks 40 and 48 (P=0.068) in an intention-to-treat analysis. Using <50 copies/mL as the endpoint, 41% of patients in the d4T/ddI/IDV arm but only 35% of patients in the ZDV/3TC/IDV arm achieved complete suppression by weeks 40-48 (P>0.2). The increase above baseline in CD4 count at week 48 was significantly greater for the d4T/ddI/IDV group as compared to the ZDV/3TC/IDV group (P=0.001). There was no significant difference in the rate of serious adverse events between the two groups.
These results demonstrate that d4T/ddI can be combined with IDV as effectively as ZDV/3TC in treatment-naive patients. The START I study, which was presented recently at ICAAC , demonstrated the similar potency of regimens combining d4T/3TC or ZDV/3TC together with a protese inhibitor. Recent studies showed similar when d4T/3TC or d4T/ddI were combined with efavirenz. Taken together these studies show that d4T/3TC, d4T/ddI, and ZDV/3TC can each be used effectively together with a third potent agent such as a PI or NNRTI. The choice of which nucleoside RT inhibitors to use as part of an initial regimen should therefore be based on patient preference, tolerability, and the potential for drug-drug interactions.
1. Squires KE. An open-label, randomized, comparative study of stavudine (d4T) + lamivudine (3TC) + indinavir (IDV) versus zidovudine (ZDV) + 3TC + IDV in treatment of HIV-infected patients: START I [Abstract 506]. 39th ICAAC, San Francisco, 1999)