A Phase II, Randomized Trial of Amprenavir as Part of Dual Protease Inhibitor Regimens (Placebo-Controlled) in Combination With Abacavir, Efavirenz, and Adefovir Dipivoxil Versus Amprenavir Alone in HIV-Infected Subjects With Prior Exposure to Approved Protease Inhibitors and Loss of Virologic Suppression as Reflected by a Plasma HIV-1 RNA Concentration >= 1,000 Copies/ml

Trial Information

A Phase II, Randomized Trial of Amprenavir as Part of Dual Protease Inhibitor Regimens (Placebo-Controlled) in Combination With Abacavir, Efavirenz, and Adefovir Dipivoxil Versus Amprenavir Alone in HIV-Infected Subjects With Prior Exposure to Approved Protease Inhibitors and Loss of Virologic Suppression as Reflected by a Plasma HIV-1 RNA Concentration >= 1,000 Copies/ml

A number of studies both within and outside the ACTG have been initiated or are in
development to try to address the issue of alternative treatments for patients who either do
not achieve or lose virologic control while receiving protease inhibitors (PIs). Amprenavir
(APV) is an attractive candidate to investigate as part of salvage regimens because: 1) it
has substantial antiretroviral activity; 2) there are preliminary in vitro and in vivo data
that suggest that resistance to this agent may be mediated in part by a unique mutation
(I50V); and 3) its cross-resistance profile to the approved PIs is uncertain.

Patients are selectively randomized to 1 of 4 study arms based on prior PI experience. Those
randomized to Arms A, B, or C receive 2 PIs, 1 of which is amprenavir (APV), and those
randomized to Arm D receive a single PI (APV) as part of their treatment regimen, as
follows:

Arm A: APV plus saquinavir soft gel capsule (SQVsgc) plus abacavir (ABC) plus efavirenz
(EFV) plus adefovir (ADV).

Arm B: APV plus indinavir (IDV) plus ABC plus EFV plus ADV. Arm C: APV plus nelfinavir (NFV)
plus ABC plus EFV plus ADV. Arm D: APV plus placebo (NFV, IDV, or SQVsgc) plus ABC plus EFV
plus ADV. All patients receive L-carnitine supplementation. All patients receive clinical
physical assessments and laboratory testing during study as follows: Weeks 2, 4, and every 4
weeks thereafter. A primary analysis is performed after the last patient has reached 24
weeks. [AS PER AMENDMENT 3/2/00: At that time, all patients are unblinded to their original
treatment assignment.] Patients who experience virologic failure are unblinded and may
choose 1 of the following 3 options: Continue study medications open-label, permanently
discontinue study medications, or selectively continue study medications [AS PER AMENDMENT
3/2/00: from the arm the patient was originally randomized to] and combine with other
approved antiretroviral agents. [AS PER AMENDMENT 3/2/00: For patients adding didanosine
(ddI) to their regimens, monitoring for the development of pancreatitis is crucial.] Final
evaluations are required for those patients who are off drug during the immediate 8-week
period following the last dose of study treatment. Beyond 8 weeks, they are followed for
incidence of death, cancer, congenital anomalies, and permanent disabilities. [AS PER
AMENDMENT 3/2/00: Gilead Sciences has terminated its U.S. development of ADV for HIV
infection. Gilead will continue to supply ADV for patients in ACTG 398 until the study
closes. Patients who are receiving ADV at the completion of the study may continue to access
ADV through the Expanded Access Program, provided that the physician and patient have
determined that continued use of ADV is beneficial.]