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Activity of the Soft Gelatin Capsule of Saquinavir (SQVsgc) in Combination With Ritonavir or Nelfinavir and Combinations of Delavirdine and/or Adefovir Dipivoxil in HIV-Infected Subjects With Prior Indinavir Use and Viral Loads From 2,000 to 200,000 Copies HIV RNA/ml

16 Years
Not Enrolling
HIV Infections

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Trial Information

Activity of the Soft Gelatin Capsule of Saquinavir (SQVsgc) in Combination With Ritonavir or Nelfinavir and Combinations of Delavirdine and/or Adefovir Dipivoxil in HIV-Infected Subjects With Prior Indinavir Use and Viral Loads From 2,000 to 200,000 Copies HIV RNA/ml

While indinavir is currently the most commonly prescribed protease inhibitor, the optimal
therapy for a person on an indinavir-containing regimen who experiences a rebound in viral
load or never experiences a decrease in viral load below 500 copies per milliliter is
unknown. Current clinical practice for such patients typically involves empiric use of a
combination of other protease inhibitors (saquinavir/nelfinavir or saquinavir/ritonavir) and
at least 1 other antiretroviral agent to which the patient has had little or no prior
exposure. This may involve the use of 1 or more reverse transcriptase inhibitors (RTIs) or
nonnucleoside reverse transcriptase inhibitors (NNRTIs). This study attempts to formally
evaluate some of these options in indinavir-experienced patients.

Patients are stratified by HIV RNA (2,000 - 20,000 copies/ml versus 20,000 - 200,000
copies/ml), and randomized to 1 of 6 treatment arms as follows:

Arm A: Saquinavir (SQV) plus ritonavir (RTV) plus delavirdine (DLV) plus adefovir dipivoxil

Arm B: SQV plus RTV plus DLV placebo plus adefovir dipivoxil. Arm C: SQV plus RTV plus DLV
plus adefovir dipivoxil. Arm D: SQV plus nelfinavir (NFV) plus DLV plus adefovir dipivoxil
placebo. Arm E: SQV plus NFV plus DLV placebo plus adefovir dipivoxil. Arm F: SQV plus NFV
plus DLV plus adefovir dipivoxil. In addition to assigned study treatment patients receive
an L-carnitine supplement.

Therapy is administered for 24 weeks. Patients who have an average HIV RNA value for Weeks
12 and 16 that is less than 5,000 copies or a least 1 log below their baseline value may
continue their assigned study treatment for an additional 24 weeks. [AS PER AMENDMENT
3/30/98: Subjects with plasma HIV RNA greater than 5,000 copies/ml may elect to continue or
discontinue study medications in the treatment extension and seek the best available
treatment.] [AS PER AMENDMENT 06/11/98: The dose of adefovir dipivoxil is reduced at or
after Week 16. Alternatively, patients may discontinue adefovir dipivoxil/placebo and
substitute appropriate antiretroviral agent(s) or add appropriate antiretroviral agent(s) to
their reduced-dose regimen. Also, at the discretion of the protocol chairperson, patients
who have been on study for more than 16 weeks may substitute appropriate FDA-approved
antiretroviral agent(s) for any study medication that must be discontinued because of
toxicity. Addition of nonnucleoside reverse transcriptase inhibitors, protease inhibitors,
or investigational agents is specifically excluded.]

Inclusion Criteria

Inclusion Criteria

Concurrent Medication:


- Chemoprophylaxis for Pneumocystis carinii pneumonia for all patients who have a CD4
cell count of equal or less than 200 cells/mm3.


- Topical and oral antifungal agents except ketoconazole and itraconazole.

- Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic

- Antibiotics.

- Systemic corticosteroids for 21 days or less for acute problems.

- Recombinant erythropoietin (rEPO) and granulocyte-colony stimulating factor (G-CSF,

- Regularly prescribed medications such as antipyretics, analgesics, allergy
medications, antidepressants, sleep medications, oral contraceptives (not as a sole
form of birth control), megestrol acetate, or testosterone.

- Alternative therapies, such as vitamins, acupuncture, and visualization techniques.

- [AS PER AMENDMENT 3/30/98: Calcium channel blockers may be used only with caution.]

Patients must have:

- HIV-1 infection documented by a licensed ELISA and confirmed by Western blot, HIV
culture, HIV antigen, plasma HIV RNA, or a second antibody test other than ELISA.

- 2,000 to 200,000 HIV-1 RNA copies/ml as measured by any Roche-certified laboratory


- using the Roche Amplicor HIV-1 Monitor] within 30 days of study entry.

- Signed, informed consent from parent or legal guardian for patients less than 18
years of age.

Prior Medication: Required:

- More than 6 months cumulative indinavir therapy.

- Stable indinavir-containing antiretroviral regimen for at least 4 weeks [2 weeks AS
PER AMENDMENT 3/30/98] prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

- Any active infection requiring acute treatment within 30 days [21 days AS PER
AMENDMENT 3/30/98] prior to study entry.

- Unexplained temperature greater than 38.5 degrees for any 7 consecutive days within
30 days prior to study entry.

- Malignancy, including Kaposi's sarcoma, that requires systemic chemotherapy.

Concurrent Medication:


- Non-protocol-specified immunomodulatory and/or antiretroviral agents.

- Systemic cytotoxic chemotherapy.

- Ketoconazole, itraconazole, rifampin, rifabutin, alprazolam, amiodarone, astemizole,
bepridil, bupropion, cisapride, clorazepate, clozapine, diazepam, encainide,
estazolam, flecainide, flurazepam, isotretinoin, meperidine, midazolam, piroxicam,
propafenone, propoxyphene, quinidine, terfenadine, triazolam, zolpidem, phenytoin,
phenobarbital, carbamazepine, and ergot alkaloids and [ AS PER AMENDMENT 3/30/98:
dexamethasone, ergot derivatives, and pimozide].


- Herbal medications.

Prior Medication:


- At least 2 weeks or more total ritonavir and/or saquinavir (hard gelatin capsule).

- NNRTIs (nevirapine, delavirdine, DMP-266, etc.), saquinavir (soft gelatin capsule),
nelfinavir, 141W94VX-478, and adefovir dipivoxil.

- Immunomodulator [systemic immunomodulator AS PER AMENDMENT 3/30/98] or
investigational drug therapy within 30 days prior to entry.

- Active immunization within 30 days [21 days AS PER AMENDMENT 3/30/98] prior to entry.

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

R Gulick

Investigator Role:

Study Chair


United States: Federal Government

Study ID:

ACTG 359



Start Date:

Completion Date:

August 1999

Related Keywords:

  • HIV Infections
  • HIV-1
  • Drug Therapy, Combination
  • HIV Protease Inhibitors
  • Ritonavir
  • Indinavir
  • RNA, Viral
  • Saquinavir
  • Delavirdine
  • Nelfinavir
  • Adenine
  • Anti-HIV Agents
  • Viral Load
  • HIV Infections
  • Acquired Immunodeficiency Syndrome



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