‘STARTING Off Right’

START I: An Open-Label, Randomized, Comparative Study of d4T + 3TC + Indinavir versus AZT + 3TC + Indinavir in Treatment Naïve HIV-Infected Patients

START II: An Open-Label, Randomized, Comparative Study of d4T + ddI + Indinavir versus ZDV + 3TC + Indinavir in Treatment Naïve HIV-Infected Patients

These two companion studies are randomized, open-label, relatively large trials (200 patients per), and were designed to compare and assess several commonly used triple combination regimens when used as initial therapy in patients who are treatment-naïve.

Both studies are identical in design, except for the drug regimens used. Patients with more than 200 CD4 cells/mL and a viral load greater than 10,000 copies/ml (as measured by Chiron's bDNA test) were assigned to one of the two arms of each study. Study investigators, led by Kathleen Squires in START I and by Joseph Eron in START II, measured the following in participating patients:

• change from baseline in viral load
• change from baseline in CD4 cell count
• percentage of patients whose viral load became undetectable (<500 copies/ml)
• incidence and severity of adverse events

An interim analysis was done after half of the total patients (i.e., 100 of 200) had been on each study for 24 weeks.

The results of both studies showed that the combination of the protease inhibitor indinavir with a number of nucleoside analogue reverse transcriptase inhibitor pairings (d4T+ddI, d4T+3TC, or AZT+3TC) can provide potent and durable suppression of HIV. All treatment combinations were roughly comparable in effect (results shown below), and in the occurrence of side effects, with slightly higher complaints of nausea and abdominal pain among people receiving AZT.

Additionally, there was a trend towards moderately higher median CD4 cell count increases in the non-AZT arms (averaging between 150-200 cell/mm³ by week 24). The START trials also underscore the range of options that patients beginning treatment can and should discuss with their doctors.

START I

This trial compared the effects of d4T + 3TC+ indinavir to those of AZT + 3TC + indinavir, with the following results.

The number of patients leaving the study before the analysis was conducted was slightly higher in the AZT + 3TC arm but this was not significant. Seven patients (14%) on the d4T + 3TC arm and 11 (22%) on the AZT + 3TC arm discontinued for reasons including side effects.

START II

In this trial the two regimens compared were d4T + ddI + indinavir and AZT + 3TC + indinavir, with the following results:

There was a somewhat high rate of discontinuation on each of the arms, for various reasons, not all drug-related. Eleven patients (22%) on the d4T + ddI arm and 12 (24%) on the AZT + 3TC arm discontinued before the analysis was conducted.