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A Study of Three Treatment Combinations Using Zidovudine Plus Lamivudine Plus Indinavir in HIV-Infected Patients

Phase 2
Completed
Conditions
HIV Infections
Registration Number
NCT00001084
Lead Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

To compare the proportion of patients who sustain suppression of plasma HIV RNA to undetectable levels \[AS PER AMENDMENT 09/19/97: below 200 copies/mL by Roche UltraSensitive assay\] among the 3 regimens during the maintenance phase.

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.

Detailed Description

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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
500
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (45)

Univ of Southern California / LA County USC Med Ctr

🇺🇸

Los Angeles, California, United States

Univ of California / San Diego Treatment Ctr

🇺🇸

San Diego, California, United States

San Francisco Gen Hosp

🇺🇸

San Francisco, California, United States

Stanford at Kaiser / Kaiser Permanente Med Ctr

🇺🇸

San Francisco, California, United States

Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium

🇺🇸

San Jose, California, United States

San Mateo AIDS Program / Stanford Univ

🇺🇸

Stanford, California, United States

Stanford Univ Med Ctr

🇺🇸

Stanford, California, United States

Harbor UCLA Med Ctr

🇺🇸

Torrance, California, United States

Univ of Colorado Health Sciences Ctr

🇺🇸

Denver, Colorado, United States

Univ of Miami School of Medicine

🇺🇸

Miami, Florida, United States

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Univ of Southern California / LA County USC Med Ctr
🇺🇸Los Angeles, California, United States

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