Know Cancer

or
forgot password

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


Phase 2
16 Years
N/A
Not Enrolling
Both
HIV Infections

Thank you

Trial Information

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


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 included. 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.]

Rollover patients from ACTG 320 are given enrollment priority and permitted to enroll in all
4 study groups; non-ACTG patients are permitted to enroll in Groups A and B if accrual
objectives are not met with ACTG 320 patients.

GROUP A:

Patients with screening plasma HIV-1 RNA concentrations below 500 copies/ml are randomized
to 1 of 2 treatment arms and stratified according to their participation in ACTG 320
(original randomization to IDV versus open-label IDV). The 2 treatment arms are as follows:

ARM A1: IDV plus ZDV (or d4T) plus 3TC plus ABC. ARM A2: IDV plus ZDV (or d4T) plus 3TC plus
ABC placebo. Patients who achieve a plasma HIV-1 RNA level of 500 copies/ml or more on 2
consecutive determinations may continue their assigned arm in a blinded fashion, or seek the
best alternative therapy selected by the local investigator or primary care physician.

GROUP B:

Nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive patients with plasma HIV-1 RNA
plasma concentrations of 500 copies/ml or more are randomized to 1 of 4 treatment arms and
stratified by plasma HIV-1 RNA concentrations (above versus below 15,000 RNA copies/ml) and
participation in ACTG 320 (original randomization to IDV versus open-label IDV). The
treatment arms are as follows:

ARM B1: ABC plus EFV plus adefovir dipivoxil plus NFV. ARM B2: ABC plus EFV plus adefovir
dipivoxil plus NFV placebo. ARM B3: 2 nucleoside reverse transcriptase inhibitors (NRTIs)
(or 1 if 2 not tolerated) (chosen from ZDV, 3TC, d4T, or didanosine [ddI]) plus EFV plus
adefovir dipivoxil plus NFV.

ARM B4: 2 NRTIs (or 1 if 2 not tolerated) (chosen from ZDV, 3TC, d4T, or ddI) plus EFV plus
adefovir dipivoxil plus NFV placebo.

GROUP C:

NNRTI-naive patients with plasma HIV-1 RNA concentrations of 500-2,000 copies/ml at
screening may elect to be randomized to a treatment arm in Group B or continue with their
current ACTG 320 regimen as follows:

ARM C: ZDV (or d4T) plus 3TC plus IDV. Patients who elect this treatment are randomized in
Group B if their plasma HIV-1 RNA concentrations are confirmed to be above 2,000 copies.

GROUP D:

NNRTI-experienced, ACTG 320 patients with screening plasma HIV-1 RNA concentrations of 500
copies/ml or more receive open-label treatment as follows:

ARM D: ABC plus EFV plus adefovir dipivoxil plus NFV. [AS PER AMENDMENT 06/29/98: Enrollment
to Group B is closed to accrual. Group A patients with HIV-1 RNA of 200 copies/ml or more on
2 consecutive determinations may continue their assigned treatment or seek best alternative
antiretroviral therapy, which may include access to ABC. Group B patients with plasma HIV-1
RNA of 500 copies/ml or more may continue their assigned treatment or seek best available
antiretroviral therapy, which may include access to ABC, EFV, and adefovir dipivoxil with
L-carnitine supplementation. Group C patients with HIV-1 RNA levels above 2,000 copies/ml
and Group D patients with levels above 500 copies/ml may no longer be randomized to a
treatment arm in Group B. Such patients may continue their assigned treatment or seek best
available therapy, which may include access to therapy as per Group B patients.] [AS PER
AMENDMENT 06/16/99: Study treatment for Groups B, C, and D has been completed. Group A
patients with a confirmed plasma HIV-2 endpoint who remain on study may have access to ABC
while on study.] [AS PER AMENDMENT 12/27/01: With Version 4.0 of the protocol, many of the
metabolic assessments and the cardiovascular risk assessment will be repeated, and a
self-reported questionnaire of body shape changes will be added. In addition, an
investigation of the effect of long-term IDV on pyuria/hematuria is added, as well as a
study of HIV-1 RNA in peripheral blood mononuclear cells (PBMCs).]

Inclusion 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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Masking: Double-Blind, Primary Purpose: Treatment

Principal Investigator

Scott Hammer

Investigator Role:

Study Chair

Authority:

United States: Federal Government

Study ID:

ACTG 372

NCT ID:

NCT00000885

Start Date:

Completion Date:

June 2003

Related Keywords:

  • HIV Infections
  • HIV-1
  • Drug Therapy, Combination
  • Zidovudine
  • HIV Protease Inhibitors
  • Lamivudine
  • Indinavir
  • RNA, Viral
  • Treatment Failure
  • Reverse Transcriptase Inhibitors
  • Anti-HIV Agents
  • Viral Load
  • HIV Infections
  • Acquired Immunodeficiency Syndrome

Name

Location

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
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
Tulane Univ School of MedicineNew Orleans, Louisiana  70112
Harvard (Massachusetts Gen Hosp)Boston, Massachusetts  02114
Beth Israel Deaconess Med CtrBoston, Massachusetts  02215
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
Duke Univ Med CtrDurham, North Carolina  27710
Ohio State Univ Hosp ClinicColumbus, Ohio  432101228
Univ of Tennessee / E Tennessee Comprehensive Hemophilia CtrKnoxville, Tennessee  37920
Johns Hopkins HospBaltimore, Maryland  21287
St Louis Regional Hosp / St Louis Regional Med CtrSt Louis, Missouri  63112
Univ of Alabama at BirminghamBirmingham, Alabama  35294
Univ of Southern California / LA County USC Med CtrLos Angeles, California  900331079
Cook County HospChicago, Illinois  60612
Univ of Iowa Hosp and ClinicIowa City, Iowa  52242
Univ of Nebraska Med CtrOmaha, Nebraska  681985130
Beth Israel Med CtrNew York, New York  10003
Carolinas Med CtrCharlotte, North Carolina  28203
Moses H Cone Memorial HospGreensboro, North Carolina  27401
Univ of CincinnatiCincinnati, Ohio  452670405
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 Kentucky LexingtonCincinnati, Ohio  45267
MetroHealth Med CtrCleveland, Ohio  441091998
Univ of Texas GalvestonGalveston, Texas  775550435
Univ Texas Health Science Ctr / Univ Texas Med SchoolHouston, Texas  77030
Queens Med CtrHonolulu, Hawaii  96816
Georgetown Univ HospWashington, District of Columbia  20037
Emory UnivAtlanta, Georgia  30308
Division of Inf Diseases/ Indiana Univ HospIndianapolis, Indiana  46202
St Vincent's Hosp / Mem Sloan-Kettering Cancer CtrNew York, New York  10021
Vanderbilt Univ Med CtrNashville, Tennessee  37203
Chelsea CtrNew York, New York  10021