Drug Interactions of Amprenavir and Efavirenz, in Combination With a Second Protease Inhibitor, in HIV-Negative Volunteers
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional

Summary: 
      The purpose of this study is to measure the blood levels of amprenavir (APV) alone, APV
      combined with efavirenz (EFV), and APV/EFV combined with a third drug (nelfinavir [NFV],
      indinavir [IDV], ritonavir soft gel capsules [RTV sgc], or saquinavir soft gel capsules [SQV
      sgc]).

      Anti-HIV therapy with 3 or 4 drugs is currently the recommended approach for treating HIV
      infections. Doctors need to know the best dosages of certain drugs when they are given in
      combination. This study will measure the blood levels of APV alone, APV combined with EFV,
      and APV/EFV plus a second PI in healthy volunteers. It will study the safety and tolerance of
      these drugs.
    

Detailed description: 
      Triple-drug antiretroviral regimens have become the recommended approach to therapy for HIV
      infection. [AS PER AMENDMENT 12/4/00: The clinical use of multiple-drug antiretroviral
      regimens containing various combinations of nucleoside reverse transcriptase inhibitors
      (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors
      (PIs) has become a widespread approach to therapy for HIV infection, especially for patients
      previously treated with PIs.] Since the introduction of PIs, a greater awareness of the
      relationship between optimal suppression of viral replication, genotypic resistance, and
      viral rebound has led to the design of more potent antiretroviral drug combinations. Two ACTG
      clinical trials addressing the issue of virologic failure utilize antiviral regimens that
      include 2 NRTIs, 2 PIs (one of which is APV), and EFV (NNRTI). Although this drug combination
      is logical, there is limited PK data to guide the dosing selection. This study enrolls
      healthy volunteers to obtain PK profiles and metabolic assessments of APV/EFV before and
      after the addition of a second PI [AS PER AMENDMENT 12/4/00: APV alone, APV combined with
      EFV, and APV/EFV combined with a second PI].

      Upon study entry, volunteers receive APV plus EFV for 2 weeks. [AS PER AMENDMENT 12/4/00:
      Volunteers receive a single dose of APV alone on Day 0, EFV alone on Days 1 to 10, and APV
      combined with EFV on Days 11 to 13.] After 2 weeks [AS PER AMENDMENT 12/4/00: After
      completion of the second PK visit], volunteers are randomized to 1 of 5 treatment arms to add
      a second PI to the APV/EFV drug combination for 2 more weeks [AS PER AMENDMENT 12/4/00: for
      at least 1 week]. The treatment arms are as follows:

      Arm A (control arm): APV and EFV alone. Arm B: APV and EFV plus IDV [AS PER AMENDMENT
      12/4/00: APV and EFV plus NFV]. Arm C: APV and EFV plus NFV [AS PER AMENDMENT 12/4/00: APV
      and EFV plus IDV]. Arm D: APV and EFV plus RTV sgc. Arm E: APV and EFV plus SQV sgc. On Day
      14, 15, or 16, volunteers return to the clinic for PK testing following the dual-drug
      regimen, and again on Day 29, 30, or 31 following the triple-drug regimen (or continued
      dual-drug regimen for Arm A). [AS PER AMENDMENT 12/4/00: Volunteers attend clinics for PK
      testing on Days 0 and 1 (first visit), after taking the dual-drug regimen for at least 3 days
      (second visit, e.g., on Day 14 or after), and after taking the triple-drug regimen (or, if in
      Arm A, after continuing on the dual-drug regimen) for at least 7 days (third visit).] Before
      each PK testing, volunteers complete an Adherence Questionnaire. [AS PER AMENDMENT 12/4/00:
      The Adherence Questionnaire is administered at the second and third PK visits.] Volunteers
      maintain a food diary. Two to three weeks after completing the drug regimen [AS PER AMENDMENT
      12/4/00: Within 2-3 weeks after the third PK visit], volunteers return to the clinic for
      evaluations and urine and blood sampling.
    

Intervention name(s): Indinavir sulfate; Ritonavir; Amprenavir; Nelfinavir mesylate; Efavirenz; Saquinavir
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Ritonavir; Nelfinavir; Indinavir; Saquinavir; Amprenavir; Efavirenz
Primary purpose: Treatment
Keywords: Drug Interactions; Drug Therapy, Combination; HIV Protease Inhibitors; Ritonavir; Dosage Forms; Saquinavir; VX 478; Anti-HIV Agents; Nelfinavir; Pharmacokinetics; efavirenz