Trial Information

A Prospective Randomized Double-Blind Trial of Three Maintenance Regimens for HIV-Infected Subjects Receiving Induction Therapy With Zidovudine, Lamivudine and Indinavir

The objective of antiretroviral therapy is to reduce HIV replication, preserve immunologic
function and delay the development of HIV-related complications. In patients administered
potent antiretroviral regimens, HIV RNA levels are reduced below 500 copies/ml of plasma and
below the level of detection of commercially available assays. This protocol attempts to
learn if a less intensive regimen can successfully sustain viral suppression after induction
with a triple-drug regimen. The study also addresses whether HIV can be eradicated in
patients following prolonged treatment with induction and maintenance regimens.

All patients will receive open label induction therapy with zidovudine (ZDV), lamivudine
(3TC) and indinavir (IDV) for 6 months. Following the 6 month induction phase, patients with
undetectable plasma HIV RNA at weeks 16, 20 and 24 will enter the maintenance phase [blinded
maintenance phase AS PER AMENDMENT 09/19/97] and be randomized to one of three maintenance
regimens, i.e., either continued ZDV/3TC/IDV (control), or ZDV/3TC/IDV placebo or ZDV
placebo/3TC placebo/IDV. Prior to randomization, patients are stratified according to entry
HIV RNA level (greater than or equal to 30,000 or less than 30,000 copies/ml) and by prior
ZDV therapy (at least 7 days or less than 7 days). After 12 months [AS PER AMENDMENT
09/19/97: 18 months] of maintenance therapy, treatment will be withdrawn at 6-month
intervals in randomly-selected patients who have achieved undetectable HIV RNA. AS PER
09/19/97 AMENDMENT: After 18 months of blinded maintenance therapy, treatment is unblinded
for patients whose HIV RNA levels remain detectable. Such patients receive optimal therapy,
either continuing the protocol regimen or initiating alternative therapy.

AS PER AMENDMENT 2/27/98: An interim review conducted in January, 1998 demonstrated that the
strategy of less intensive antiviral therapy after 6 months of IDV/3TC/ZDV induction therapy
is less effective than continuation of triple drug therapy except for ZDV-naive patients
assigned to ZDV/3TC. Therefore, the maintenance phase of this study has been discontinued.

Patients currently on blinded maintenance are unblinded immediately and have the option of
reinitiating open-label triple therapy with IDV/3TC/ZDV or discontinuing study treatment.
Patients currently on induction may register for continued open-label triple therapy or may
discontinue study treatment. This amendment allows treatment extension so that subjects may
receive open-label triple therapy until May 31, 1998. At that time, a rollover protocol or
another modification with a longer period of drug supply may become available. Patients who
choose to go off treatment are followed until May 31, 1998.

AS PER AMENDMENT 04/23/98: This study will now provide treatment with open-label ZDV/3TC/IDV
until August 1, 1998. A rollover protocol or another 343 protocol modification with a longer
period of drug supply may become available, but this cannot be guaranteed.

AS PER AMENDMENT 06/19/98: This study will now provide treatment with open-label ZDV/3TC/IDV
until either November 1, 1998 or until 3 months after the rollover study (A5025) is
available to the study sites (whichever comes first).