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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


N/A
16 Years
N/A
Not Enrolling
Both
HIV Infections

Thank you

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
placebo.

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:

Required:

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

Allowed:

- Topical and oral antifungal agents except ketoconazole and itraconazole.

- Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic
infections.

- Antibiotics.

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

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

- 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
[AS

PER AMENDMENT 3/30/98:

- 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:

Excluded:

- 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].

Avoided:

- Herbal medications.

Prior Medication:

Excluded:

- 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:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

R Gulick

Investigator Role:

Study Chair

Authority:

United States: Federal Government

Study ID:

ACTG 359

NCT ID:

NCT00000892

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

Name

Location

San Francisco Gen HospSan Francisco, California  941102859
Bellevue Hosp / New York Univ Med CtrNew York, New York  10016
Univ of Rochester Medical CenterRochester, New York  14642
Julio ArroyoWest Columbia, South Carolina  29169
UCLA CARE CtrLos Angeles, California  90095
Univ of California / San Diego Treatment CtrSan Diego, California  921036325
Stanford at Kaiser / Kaiser Permanente Med CtrSan Francisco, California  94115
Harbor UCLA Med CtrTorrance, California  90502
Univ of Colorado Health Sciences CtrDenver, Colorado  80262
Univ of Miami School of MedicineMiami, Florida  331361013
Rush Presbyterian - Saint Luke's Med CtrChicago, Illinois  60612
Northwestern Univ Med SchoolChicago, Illinois  60611
Indiana Univ HospIndianapolis, Indiana  462025250
Beth Israel Deaconess - West CampusBoston, Massachusetts  02215
Boston Med CtrBoston, Massachusetts  02118
Univ of MinnesotaMinneapolis, Minnesota  55455
SUNY / Erie County Med Ctr at BuffaloBuffalo, New York  14215
Cornell Univ Med CtrNew York, New York  10021
Mount Sinai Med CtrNew York, New York  10029
Univ of North CarolinaChapel Hill, North Carolina  275997215
Ohio State Univ Hosp ClinicColumbus, Ohio  432101228
Univ of Tennessee / E Tennessee Comprehensive Hemophilia CtrKnoxville, Tennessee  37920
Univ of WashingtonSeattle, Washington  98105
Johns Hopkins HospBaltimore, Maryland  21287
Univ of Alabama at BirminghamBirmingham, Alabama  35294
Univ of Southern California / LA County USC Med CtrLos Angeles, California  900331079
Cook County HospChicago, Illinois  60612
Beth Israel Med CtrNew York, New York  10003
Univ of CincinnatiCincinnati, Ohio  452670405
Univ of Pennsylvania at PhiladelphiaPhiladelphia, Pennsylvania  19104
Santa Clara Valley Med Ctr / AIDS Community Rsch ConsortiumSan Jose, California  951282699
Stanford Univ Med CtrStanford, California  943055107
San Mateo AIDS Program / Stanford UnivStanford, California  943055107
Howard UnivWashington, District of Columbia  20059
Univ of HawaiiHonolulu, Hawaii  96816
Louis A Weiss Memorial HospChicago, Illinois  60640
Methodist Hosp of Indiana / Life Care ClinicIndianapolis, Indiana  46202
Univ of Texas GalvestonGalveston, Texas  775550435
Queens Med CtrHonolulu, Hawaii  96816
State of MD Div of Corrections / Johns Hopkins Univ HospBaltimore, Maryland  212052196
St Vincent's Hosp / Mem Sloan-Kettering Cancer CtrNew York, New York  10021
Willow ClinicMenlo Park, California  94025
Univ of Pittsburgh Med CtrPittsburgh, Pennsylvania  15213
Chelsea CtrNew York, New York  10021
Brown Univ School of MedicineProvidence, Rhode Island  02908