A Study to Compare the Effectiveness of a Four Drug Anti-HIV Regimen Given Alone or in Combination With GM-CSF or IL-12 to HIV-Positive Patients
|First Submitted Date ICMJE||November 2, 1999|
|First Posted Date ICMJE||August 31, 2001|
|Last Update Posted Date||May 18, 2012|
|Start Date ICMJE||Not Provided|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00000896 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||A Study to Compare the Effectiveness of a Four Drug Anti-HIV Regimen Given Alone or in Combination With GM-CSF or IL-12 to HIV-Positive Patients|
|Official Title ICMJE||A Randomized Controlled Trial to Compare the Efficacy of a Four Drug Antiretroviral Regimen Alone or in Combination With GM-CSF or IL-12 Administered to HIV-1 Infected Subjects as Measured by the Characteristics of Viral Decay|
The purpose of this study is to examine how the level of HIV is reduced in the blood when anti-HIV therapy is initiated. This study will also evaluate whether adding GM-CSF or IL-12 to the anti-HIV drug regimen will increase the rate that HIV is reduced.
The anti-HIV drugs used in this study will include lamivudine (3TC), zidovudine (ZDV), indinavir (IDV), nevirapine (NVP), and stavudine (d4T). All have been used successfully to treat HIV. GM-CSF has been used to treat certain blood disorders; it will be used as an experimental drug in this study. IL-12 (interleukin-12) is a protein found naturally in the body that is thought to boost the immune system. Although GM-CSF and IL-12 have no direct effect against HIV, these drugs may improve the ability of the immune system to fight the virus.
Potent antiretroviral therapies that suppress HIV replication have permitted mathematical modeling of the dynamics of HIV infection and clearance by measurement of the decay of viral load in plasma. When de nova infection is blocked by antiretroviral therapy, the viral load decreases exponentially after a short initial lag time ("shoulder"). This rapid decline is followed by a slower second-phase decay. The intent of this study is to utilize four antiretroviral agents (zidovudine, lamivudine, nevirapine, indinavir) and very frequent measures of viral load to explore the drug-specific kinetics of the "shoulder". The decay of long-lived HIV-infected tissue macrophages is thought to be the major determinant of the slow second phase. Further, the study intends to use immune modulating agents with the potential to increase the turnover of infected macrophages, GM-CSF or IL-12, to accelerate the second phase of viral decay.
Patients are assigned to Group A (16 patients) or to Group B (8 patients). Patients in Group A are randomized to 1 of the following 4 initial treatment arms:
ARM A: Final dose combination (FDC) Zidovudine (ZDV)/Lamivudine (3TC). ARM B: Nevirapine (NVP). ARM C: Indinavir (IDV). ARM D: FDC ZDV/3TC plus NVP plus IDV. The initial regimen is maintained over the first 72 hours and blood for viral dynamic evaluations collected while patients are maintained as inpatients. Then, patients in Arms A, B, and C initiate FDC ZDV/3TC plus NVP plus IDV.
Patients assigned to Group B begin the following 4-drug regimen on Day 0:
ARM E: FDC ZDV/3TC plus NVP plus IDV.
On Day 7, patients in both Groups A and B are randomized to receive one of the following therapies in addition to their 4-drug regimen:
ARM F: GM-CSF daily for 2 weeks, then thrice weekly (MWF). ARM G: IL-12 twice weekly. ARM H: No immune modulation. Patients may be hospitalized to initiate immune modulation or may be treated as outpatients. Immune modulation is discontinued after Week 14. Patients maintain their 4-drug regimen through Week 48. [AS PER AMENDMENT 6/11/99: The study duration has been extended to 96 weeks.] Hepatitis A vaccine (inactivated) is administered on Weeks 16 and 40 [AS PER AMENDMENT 2/13/98: to patients whose baseline hepatitis A serology was negative].
|Study Type ICMJE||Interventional|
|Study Phase||Not Provided|
|Study Design ICMJE||Masking: None (Open Label)
Primary Purpose: Treatment
|Condition ICMJE||HIV Infections|
|Study Arms||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||October 2000|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
You may be eligible for this study if you:
You will not be eligible for this study if you:
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00000896|
|Other Study ID Numbers ICMJE||ACTG 387
11346 ( Registry Identifier: DAIDS ES Registry Number )
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||National Institute of Allergy and Infectious Diseases (NIAID)|
|Study Sponsor ICMJE||National Institute of Allergy and Infectious Diseases (NIAID)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institute of Allergy and Infectious Diseases (NIAID)|
|Verification Date||May 2012|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP