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HIV InfectionsNCT00000892

A Study of Several Anti-HIV Drug Combinations in HIV-Infected Patients Who Have Used Indinavir

A study testing Ritonavir, Nelfinavir mesylate and Levocarnitine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 45 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

To compare the proportion of patients whose plasma HIV-1 RNA is below 500 copies/ml after 16 weeks of treatment. To assess the safety, toxicity, and tolerance of each treatment arm. Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
HIV Infections
What is being tested?
Ritonavir, Nelfinavir mesylate and Levocarnitine
How many people
300 participants
Where
45 sitesUnited States
Study dates
Start not givento Aug 1999
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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:
Show all 18Show fewer
  • 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.

Trial locations and contacts

45 sites in 1 country.

45 sites in 1 country

United States45 sites

  • State of MD Div of Corrections / Johns Hopkins Univ Hosp

    Baltimore, Maryland, 212052196

  • Johns Hopkins Hosp

    Baltimore, Maryland, 21287

  • Univ of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Boston Med Ctr

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess - West Campus

    Boston, Massachusetts, 02215

  • SUNY / Erie County Med Ctr at Buffalo

    Buffalo, New York, 14215

  • Univ of North Carolina

    Chapel Hill, North Carolina, 275997215

  • Northwestern Univ Med School

    Chicago, Illinois, 60611

  • Cook County Hosp

    Chicago, Illinois, 60612

  • Rush Presbyterian - Saint Luke's Med Ctr

    Chicago, Illinois, 60612

  • Louis A Weiss Memorial Hosp

    Chicago, Illinois, 60640

  • Univ of Cincinnati

    Cincinnati, Ohio, 452670405

  • Ohio State Univ Hosp Clinic

    Columbus, Ohio, 432101228

  • Univ of Colorado Health Sciences Ctr

    Denver, Colorado, 80262

  • Univ of Texas Galveston

    Galveston, Texas, 775550435

  • Queens Med Ctr

    Honolulu, Hawaii, 96816

  • Univ of Hawaii

    Honolulu, Hawaii, 96816

  • Indiana Univ Hosp

    Indianapolis, Indiana, 462025250

  • Methodist Hosp of Indiana / Life Care Clinic

    Indianapolis, Indiana, 46202

  • Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr

    Knoxville, Tennessee, 37920

  • Univ of Southern California / LA County USC Med Ctr

    Los Angeles, California, 900331079

  • UCLA CARE Ctr

    Los Angeles, California, 90095

  • Willow Clinic

    Menlo Park, California, 94025

  • Univ of Miami School of Medicine

    Miami, Florida, 331361013

  • Univ of Minnesota

    Minneapolis, Minnesota, 55455

  • Beth Israel Med Ctr

    New York, New York, 10003

  • Bellevue Hosp / New York Univ Med Ctr

    New York, New York, 10016

  • Chelsea Ctr

    New York, New York, 10021

  • Cornell Univ Med Ctr

    New York, New York, 10021

  • St Vincent's Hosp / Mem Sloan-Kettering Cancer Ctr

    New York, New York, 10021

  • Mount Sinai Med Ctr

    New York, New York, 10029

  • Univ of Pennsylvania at Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Univ of Pittsburgh Med Ctr

    Pittsburgh, Pennsylvania, 15213

  • Brown Univ School of Medicine

    Providence, Rhode Island, 02908

  • Univ of Rochester Medical Center

    Rochester, New York, 14642

  • Univ of California / San Diego Treatment Ctr

    San Diego, California, 921036325

  • San Francisco Gen Hosp

    San Francisco, California, 941102859

  • Stanford at Kaiser / Kaiser Permanente Med Ctr

    San Francisco, California, 94115

  • Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium

    San Jose, California, 951282699

  • Univ of Washington

    Seattle, Washington, 981224304

  • San Mateo AIDS Program / Stanford Univ

    Stanford, California, 943055107

  • Stanford Univ Med Ctr

    Stanford, California, 943055107

  • Harbor UCLA Med Ctr

    Torrance, California, 90502

  • Howard Univ

    Washington D.C., District of Columbia, 20059

  • Julio Arroyo

    West Columbia, South Carolina, 29169

Other trials in United States

About this study

Official title: 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

To compare the proportion of patients whose plasma HIV-1 RNA is below 500 copies/ml after 16 weeks of treatment. To assess the safety, toxicity, and tolerance of each treatment arm.

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.

Read the detailed description

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.]

Conditions
HIV Infections
Being tested
Ritonavir, Nelfinavir mesylate, Levocarnitine, Adefovir dipivoxil, Saquinavir
Keywords
HIV-1, Drug Therapy, Combination, HIV Protease Inhibitors, Ritonavir, Indinavir, RNA, Viral, Saquinavir, Delavirdine, Nelfinavir, Adenine, Anti-HIV Agents, Viral Load
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RitonavirDrug

  • Nelfinavir mesylateDrug

  • LevocarnitineDrug

  • Adefovir dipivoxilDrug

  • SaquinavirDrug

  • Delavirdine mesylateDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Study completionAug 1999

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Enrolment
300 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000892
Sponsor's protocol ID
ACTG 359
Other IDs
11324
Status last verified
Oct 2021
First submitted
2 Nov 1999
Last updated
4 Nov 2021
Results posted
No

Publications

  • Gulick RM, Hu XJ, Fiscus S, Fletcher CV, Haubrich R, Cheng H, Lagakos S, Acosta E, Swanstrom R, Mills C, Snyder S, Fischl M, Pettinelli C, Katzenstein D. Durability of salvage therapy with saquinavir SGC (SQV) in combination with ritonavir (RTV) or nelfinavir (NFV) plus delavirdine (DLV), adefovir dipivoxil (ADV), or both; ACTG 359: 48-week final results. 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 338)

  • Acosta EP, Gulick R, Katzenstein D, Haubrich R, Fischl M, Raasch R, Mills C, Pettinelli C, Remmel RP, Fletcher CV. Pharmacokinetic (PK) evaluation of saquinavir soft gel capsules (SQV)/ritonavir (RTV) or sqv/nelfinavir (NFV) in combination with delavirdine (DLV) and/or adefovir dipivoxil (ADV) - - ACTG 359. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:136 (abstract no 365)

  • Gulick RM, et al. Salvage therapy with saquinavir sgc (SQV) in combination with ritonavir (RTV) or nelfinavir (NFV) and delavirdine (DLV), adefovir dipivoxil (ADV), or both-ACTG 359. Second International Workshop on Salvage Therapy for HIV Infection. 1999 May 19-21

  • Fletcher CV, Testa MA, Haubrich R, Brundage R, Jiang H, Ickovics J, Martinez A, Snyder S, Gulick R. Relationships among Four Measures of Medication Adherence and Virologic Response in ACTG 359. 10th Conference on Retroviruses and Oppurtunistic Infections. Feb 2003. Abstract 577.

  • Gulick RM, Hu XJ, Fiscus SA, Fletcher CV, Haubrich R, Cheng H, Acosta E, Lagakos SW, Swanstrom R, Freimuth W, Snyder S, Mills C, Fischl M, Pettinelli C, Katzenstein D. Randomized study of saquinavir with ritonavir or nelfinavir together with delavirdine, adefovir, or both in human immunodeficiency virus-infected adults with virologic failure on indinavir: AIDS Clinical Trials Group Study 359. J Infect Dis. 2000 Nov;182(5):1375-84. doi: 10.1086/315867. Epub 2000 Oct 9.

    PubMed 11023461

  • Gulick RM, Hu XJ, Fiscus SA, Fletcher CV, Haubrich R, Cheng H, Acosta E, Lagakos SW, Swanstrom R, Freimuth W, Snyder S, Mills C, Fischl M, Pettinelli C, Katzenstein D. Durability of response to treatment among antiretroviral-experienced subjects: 48-week results from AIDS Clinical Trials Group Protocol 359. J Infect Dis. 2002 Sep 1;186(5):626-33. doi: 10.1086/342681. Epub 2002 Aug 9.

    PubMed 12195349

  • Fletcher CV, Jiang H, Brundage RC, Acosta EP, Haubrich R, Katzenstein D, Gulick RM. Sex-based differences in saquinavir pharmacology and virologic response in AIDS Clinical Trials Group Study 359. J Infect Dis. 2004 Apr 1;189(7):1176-84. doi: 10.1086/382754. Epub 2004 Mar 16.

    PubMed 15031785

  • Swanstrom R, Bosch RJ, Katzenstein D, Cheng H, Jiang H, Hellmann N, Haubrich R, Fiscus SA, Fletcher CV, Acosta EP, Gulick RM; AIDS Clinical Trials Group Protocol 359 Team. Weighted phenotypic susceptibility scores are predictive of the HIV-1 RNA response in protease inhibitor-experienced HIV-1-infected subjects. J Infect Dis. 2004 Sep 1;190(5):886-93. doi: 10.1086/422692. Epub 2004 Jul 23.

    PubMed 15295692

  • Fletcher CV, Testa MA, Brundage RC, Chesney MA, Haubrich R, Acosta EP, Martinez A, Jiang H, Gulick RM. Four measures of antiretroviral medication adherence and virologic response in AIDS clinical trials group study 359. J Acquir Immune Defic Syndr. 2005 Nov 1;40(3):301-6. doi: 10.1097/01.qai.0000180078.53321.6a.

    PubMed 16249704

  • Haubrich RH, Jiang H, Swanstrom R, Bates M, Katzenstein D, Petch L, Fletcher CV, Fiscus SA, Gulick RM; AIDS Clinical Trials Group Protocol 359 Team. Non-nucleoside phenotypic hypersusceptibility cut-point determination from ACTG 359. HIV Clin Trials. 2007 Mar-Apr;8(2):63-7. doi: 10.1310/hct0802-63.

    PubMed 17507321

Questions about this trial

What is this clinical trial studying?

A study testing Ritonavir, Nelfinavir mesylate and Levocarnitine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 45 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 45 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00000892, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2021.

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