Treatment Success and Failure in HIV-Infected Subjects Receiving Indinavir in Combination With Nucleoside Analogs: A Rollover Study for ACTG 320

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000885
First received: November 2, 1999
Last updated: August 15, 2012
Last verified: August 2012
  Purpose

Group A:

To compare the time to confirmed virologic failure (2 consecutive plasma HIV-RNA concentrations of 500 copies/ml or more) between the treatment arms: abacavir (ABC) or placebo in combination with zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV). To evaluate the safety and tolerability of these treatment arms. [AS PER AMENDMENT 06/16/99: To compare the time to confirmed treatment failure, permanent discontinuation of treatment, or death between the treatment arms.] [AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is applicable.]

Group B:

To compare the proportion of patients who achieve plasma HIV-1 RNA concentrations below 500 copies/ml, as assessed by the standard Roche Amplicor assay at Week 16, or to compare the absolute changes in plasma HIV-1 RNA concentrations at Week 16 across the treatment arms: ABC or approved nucleoside analogs and nelfinavir (NFV) or placebo in combination with efavirenz (EFV) and adefovir dipivoxil. To compare the safety and tolerability of these treatment arms.

Group C:

To monitor plasma HIV-1 RNA trajectory over time and determine the time to a confirmed plasma HIV-1 RNA concentration above 2,000 copies/ml on 2 consecutive determinations for patients treated with ZDV or stavudine (d4T) plus 3TC and IDV.

Group D:

To evaluate plasma HIV-1 RNA responses at Weeks 16 and 48. To evaluate the safety and tolerability of the treatment arms: ABC, EFV, adefovir dipivoxil, and NFV.

This study explores new treatment options for ACTG 320 enrollees (and, if needed, a limited number of non-ACTG 320 volunteers) who have been receiving ZDV (or d4T) plus 3TC and IDV and are currently exhibiting a range of virologic responses. By dividing the study into the corresponding, nonsequential cohorts (Groups A, B, C, D), different approaches to evaluating virologic success, i.e., undetectable plasma HIV-1 RNA levels, and virologic failure, i.e., plasma HIV-1 RNA levels of 500 copies/ml or more [AS PER AMENDMENT 12/27/01: 200 copies/ml or more], are explored while maintaining long-term follow-up of ACTG 320 patients. [AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is applicable. This study will examine the question of whether intensification of therapy can prolong the virologic benefit in individuals whose plasma HIV-1 RNA concentrations have been below the limits of assay detection on ZDV (or d4T) plus 3TC plus IDV.]


Condition Intervention Phase
HIV Infections
Drug: Indinavir sulfate
Drug: Abacavir sulfate
Drug: Nelfinavir mesylate
Drug: Efavirenz
Drug: Levocarnitine
Drug: Adefovir dipivoxil
Drug: Lamivudine
Drug: Stavudine
Drug: Zidovudine
Drug: Didanosine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase II Study of the Prolongation of Virologic Success (ACTG 372A) and Options for Virologic Failure (ACTG B/C/D) in HIV-Infected Subjects Receiving Indinavir in Combination With Nucleoside Analogs: A Rollover Study for ACTG 320

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 440
Study Completion Date: June 2003
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Required:

  • Chemoprophylaxis for Pneumocystis carinii pneumonia for all patients with a CD4 cell count of 200 cells/mm3 or less.

Allowed:

  • Treatment, maintenance, or chemoprophylaxis, including topical and/or oral antifungal agents unless otherwise excluded by the protocol.
  • All antibiotics as clinically indicated, unless otherwise excluded in the protocol.
  • Systemic corticosteroid use for 21 days or less for acute problems as medically indicated. Chronic corticosteroid use is not permitted, unless it is within physiologic replacement levels. Study team must be contacted in these instances.
  • rEPO and G-CSF as medically indicated.
  • Regularly prescribed medications such as [AS PER AMENDMENT 06/29/98: alternative, FDA-approved antiretrovirals not supplied by the study] [AS PER AMENDMENT 12/27/01: or unapproved antiretrovirals available by expanded access (when permanently discontinued from randomized study treatment)], antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives, megestrol acetate, testosterone, or any other medications not otherwise excluded by the protocol, as medically indicated.
  • [AS PER AMENDMENT 12/27/01: Supplemental and] alternative therapies such as vitamins, acupuncture, and visualization techniques.

Recommended as an alternative agent for chemoprophylaxis against Mycobacterium avium complex for patients randomized to EFV in Group B or D:

  • clarithromycin or azithromycin.

Patients must have:

  • HIV-1 infection as documented by any licensed ELISA test kit and confirmed by either a Western Blot, HIV culture, HIV antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA at any time prior to study entry.

Non-ACTG patients:

  • Documented CD4 cell count of 200 cells/mm3 or less at the time of initiation of ZDV (or d4T) plus 3TC plus IDV.
  • Signed, informed consent from a parent or legal guardian for patients under 18 years of age.

Prior Medication:

Required:

Non-ACTG 320 patients:

  • At least 3 months prior therapy with ZDV (or d4T) plus 3TC plus IDV and continued receipt of ZDV (or d4T) plus 3TC plus IDV until enrollment. IDV and 3TC must have been initiated concurrently.

ACTG patients:

  • Randomization to the ZDV (or d4T) plus 3TC plus IDV combination arm or receipt of open-label prior to unblinding and maintenance of that treatment as participation in ACTG 320.

Group D:

  • Prior NNRTI-exposure.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions and symptoms are excluded:

  • Unexplained temperature above 38.5 C for any 7 days or chronic diarrhea, defined as more than 3 liquid stools per day persisting for 15 days, within 30 days prior to study treatment.
  • AIDS-related malignancy, other than minimal Kaposi's sarcoma that requires systemic chemotherapy. Minimal Kaposi's sarcoma is defined as 5 or fewer cutaneous lesions and no visceral disease or tumor-associated edema that does not require systemic therapy.
  • Documented or suspected acute hepatitis within 30 days prior to study entry, irrespective of laboratory values.

Concurrent Medication:

Excluded:

  • All antiretroviral therapies other than study [AS PER AMENDMENT 06/16/99: provided] medications, [AS PER AMENDMENT 06/16/99: unless approved by the protocol chairs] [AS PER AMENDMENT 12/27/01: while on original randomized treatment.]
  • Rifabutin and rifampin.
  • Investigational agents without specific approval from the protocol chair.
  • Systemic cytotoxic chemotherapy.
  • Oral ketoconazole and itraconazole. NOTE: Itraconazole may be permitted for Group B and Group D patients if fluconazole is not an option.
  • Terfenadine, astemizole, cisapride, triazolam, midazolam, amiodarone, quinine, ergot derivatives, isotretinoin, [AS PER AMENDMENT 12/27/01: pimozide, St.John's Wort, and milk thistle.]
  • [AS PER AMENDMENT 12/27/01: Concomitant use of lovastatin or simvastatin is not recommended because of potential drug interactions. Pravastatin or atorvastatin may be used after consultation with the Study Team.]

To be avoided:

  • Herbal medications.

Prior Medication:

Excluded:

  • Any prior protease inhibitor therapy other than indinavir.
  • Interferons, interleukins, or HIV vaccines within 30 days prior to study entry.
  • Any experimental therapy within 30 days prior to study entry.
  • Rifampin, rifabutin, ketoconazole, or itraconazole within 14 days of study entry.

Non-ACTG patients:

  • Acute therapy for an infection or other medical illness within 14 days prior to study therapy.
  • NNRTI therapy prior to study entry (with the exception of Group D).
  • Recombinant erythropoietin (rEPO), granulocyte colony-stimulating factor (G-CSF, filgrastim), or granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim) within 30 days prior to study entry.

Caution should be taken in the consumption of alcoholic beverages with study medications.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000885

  Show 53 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Scott Hammer
  More Information

Additional Information:
Publications:
Henry K, Zackin R, Dube M, Hammer S, Currier J. ACTG 5056: metabolic status and cardiovascular disease risk for a cohort of HIV-1-infected persons durably suppressed on an indinavir-containing regimen (ACTG 372A). 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 656)
Hammer S, Squires K, Degruttola V, Fischl M, Bassett R, Demeter L, Hertogs K, Larder B. Randomized trial of abacavir (ABC) & nelfinavir (NFV) in combination with efavirenz (EFV) & adefovir dipivoxil (ADV) as salvage therapy in patients with virologic failure receiving indinavir (IDV). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:159 (abstract no 490)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000885     History of Changes
Other Study ID Numbers: ACTG 372, 11333, ACTG 701, ACTG 702, ACTG 706
Study First Received: November 2, 1999
Last Updated: August 15, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
HIV-1
Drug Therapy, Combination
Zidovudine
HIV Protease Inhibitors
Lamivudine
Indinavir
RNA, Viral
Treatment Failure
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Carnitine
Didanosine
Zidovudine
Stavudine
Adefovir
Adefovir dipivoxil
Lamivudine
Reverse Transcriptase Inhibitors
Efavirenz
Abacavir
Indinavir
Nelfinavir
HIV Protease Inhibitors
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014