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A Prospective Randomized Double-Blind Trial of Three Maintenance Regimens for HIV-Infected Subjects Receiving Induction Therapy With Zidovudine, Lamivudine and Indinavir


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

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Trial Information

A Prospective Randomized Double-Blind Trial of Three Maintenance Regimens for HIV-Infected Subjects Receiving Induction Therapy With Zidovudine, Lamivudine and Indinavir


The objective of antiretroviral therapy is to reduce HIV replication, preserve immunologic
function and delay the development of HIV-related complications. In patients administered
potent antiretroviral regimens, HIV RNA levels are reduced below 500 copies/ml of plasma and
below the level of detection of commercially available assays. This protocol attempts to
learn if a less intensive regimen can successfully sustain viral suppression after induction
with a triple-drug regimen. The study also addresses whether HIV can be eradicated in
patients following prolonged treatment with induction and maintenance regimens.

All patients will receive open label induction therapy with zidovudine (ZDV), lamivudine
(3TC) and indinavir (IDV) for 6 months. Following the 6 month induction phase, patients with
undetectable plasma HIV RNA at weeks 16, 20 and 24 will enter the maintenance phase [blinded
maintenance phase AS PER AMENDMENT 09/19/97] and be randomized to one of three maintenance
regimens, i.e., either continued ZDV/3TC/IDV (control), or ZDV/3TC/IDV placebo or ZDV
placebo/3TC placebo/IDV. Prior to randomization, patients are stratified according to entry
HIV RNA level (greater than or equal to 30,000 or less than 30,000 copies/ml) and by prior
ZDV therapy (at least 7 days or less than 7 days). After 12 months [AS PER AMENDMENT
09/19/97: 18 months] of maintenance therapy, treatment will be withdrawn at 6-month
intervals in randomly-selected patients who have achieved undetectable HIV RNA. AS PER
09/19/97 AMENDMENT: After 18 months of blinded maintenance therapy, treatment is unblinded
for patients whose HIV RNA levels remain detectable. Such patients receive optimal therapy,
either continuing the protocol regimen or initiating alternative therapy.

AS PER AMENDMENT 2/27/98: An interim review conducted in January, 1998 demonstrated that the
strategy of less intensive antiviral therapy after 6 months of IDV/3TC/ZDV induction therapy
is less effective than continuation of triple drug therapy except for ZDV-naive patients
assigned to ZDV/3TC. Therefore, the maintenance phase of this study has been discontinued.

Patients currently on blinded maintenance are unblinded immediately and have the option of
reinitiating open-label triple therapy with IDV/3TC/ZDV or discontinuing study treatment.
Patients currently on induction may register for continued open-label triple therapy or may
discontinue study treatment. This amendment allows treatment extension so that subjects may
receive open-label triple therapy until May 31, 1998. At that time, a rollover protocol or
another modification with a longer period of drug supply may become available. Patients who
choose to go off treatment are followed until May 31, 1998.

AS PER AMENDMENT 04/23/98: This study will now provide treatment with open-label ZDV/3TC/IDV
until August 1, 1998. A rollover protocol or another 343 protocol modification with a longer
period of drug supply may become available, but this cannot be guaranteed.

AS PER AMENDMENT 06/19/98: This study will now provide treatment with open-label ZDV/3TC/IDV
until either November 1, 1998 or until 3 months after the rollover study (A5025) is
available to the study sites (whichever comes first).

Inclusion Criteria


Inclusion Criteria

Patients must have:

- Documented HIV infection.

- A CD4 cell count >= 200 cells/mm3 within 90 days prior to study entry.

- Plasma HIV RNA >= 1000 copies/ml within 90 days prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients with any of the following conditions or symptoms are excluded:

- A malignancy that requires systemic chemotherapy.

Concurrent Medication:

Excluded:

- Oral ketoconazole (Nizoral), terfenadine (Seldane), astemizole (Hismanal), cisapride
(Propulsid), triazolam (Halcion) or midazolam (Versed).

- All antiretroviral therapies other than study medications.

- Rifabutin and rifampin.

- Investigational drugs and vaccines.

- Systemic cytotoxic chemotherapy.

- Interferon, interleukins, GM-CSF and HIV vaccines.

Patients with any of the following prior conditions are excluded:

- Unexplained temperature > 38.5 degrees C for any 7 days within 30 days prior to study
entry.

- Chronic diarrhea as defined as > 3 liquid stools per day persisting for 15 days
within 30 days prior to study entry.

- Proven or suspected acute hepatitis within 30 days prior to study entry, even if AST
and ALT are <= 5.0 X ULN (upper limit of normal).

- A history of >= Grade 2 bilateral peripheral neuropathy within 60 days prior to study
entry.

- A history of intolerance to 300 mg/day of ZDV defined as any toxicity requiring a
dose reduction or termination of ZDV.

Prior Medication:

Excluded:

- Acute therapy for an infection or other medical illness within 14 days prior to study
entry.

- Any prior therapy with 3TC or experimental drug 1592.

- More than 2 weeks of lifetime exposure to protease inhibitor therapy; any exposure
within 14 days prior to study entry.

- Interferons, interleukins, GM-CSF or HIV vaccines within 30 days prior to study
entry.

- Any experimental therapy (drugs or vaccines) within 30 days prior to study entry.

- Rifampin or rifabutin within 14 days prior to study entry.

- Systemic cytotoxic chemotherapy within 30 days prior to study entry.

- Oral ketoconazole (Nizoral), terfenadine (Seldane), astemizole (Hismanal), cisapride
(Propulsid), triazolam (Halcion) or midazolam (Versed).

Type of Study:

Interventional

Study Design:

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

Principal Investigator

Havlir D

Investigator Role:

Study Chair

Authority:

United States: Federal Government

Study ID:

ACTG 343

NCT ID:

NCT00001084

Start Date:

Completion Date:

December 1997

Related Keywords:

  • HIV Infections
  • Prospective Studies
  • Drug Therapy, Combination
  • Zidovudine
  • HIV Protease Inhibitors
  • Lamivudine
  • Indinavir
  • RNA, Viral
  • Reverse Transcriptase Inhibitors
  • 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
Mem Sloan - Kettering Cancer CtrNew York, New York  10021
Univ of Rochester Medical CenterRochester, New York  14642
Julio ArroyoWest Columbia, South Carolina  29169
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
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 - West CampusBoston, Massachusetts  02215
Univ of MinnesotaMinneapolis, Minnesota  55455
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 WashingtonSeattle, Washington  98105
Johns Hopkins HospBaltimore, Maryland  21287
St Louis Regional Hosp / St Louis Regional Med CtrSt Louis, Missouri  63112
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
Hennepin County Med ClinicMinneapolis, Minnesota  55415
St Paul Ramsey Med CtrSt Paul, Minnesota  55101
Univ of Nebraska Med CtrOmaha, Nebraska  681985130
Beth Israel Med CtrNew York, New York  10003
Saint Clare's Hosp and Health CtrNew York, New York  10019
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
Univ of HawaiiHonolulu, Hawaii  96816
MetroHealth Med CtrCleveland, Ohio  441091998
Case Western Reserve UnivCleveland, Ohio  44106
Univ of Texas GalvestonGalveston, Texas  775550435
Queens Med CtrHonolulu, Hawaii  96816
Emory UnivAtlanta, Georgia  30308
Division of Inf Diseases/ Indiana Univ HospIndianapolis, Indiana  46202
Tulane Med Ctr HospNew Orleans, Louisiana  70112
State of MD Div of Corrections / Johns Hopkins Univ HospBaltimore, Maryland  212052196