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
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Indinavir sulfate (Drug); Lamivudine/Zidovudine (Drug); Hepatitis A Vaccine (Inactivated) (Biological); Interleukin-12 (Drug); Nevirapine (Drug); Stavudine (Drug); Sargramostim (Drug)
Phase: N/A
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Rhonda G. Kost, Study Chair
David Ho, Study Chair
Summary
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.
Clinical Details
Official title: 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
Study design: Treatment, Open Label, Pharmacokinetics Study
Detailed description:
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].
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria
You may be eligible for this study if you:
- Are HIV-positive.
- Have a CD4 cell count greater than or equal to 300 cells/ml within 30 days prior to
study entry.
- Have a plasma viral load (level of HIV in the blood) of greater than or equal to
20,000 copies/ml within 30 days of study entry.
- Are at least 18 years old.
- Agree to practice abstinence or use effective methods of birth control during the
study.
Exclusion Criteria
You will not be eligible for this study if you:
- Have taken anti-HIV medication for more than 7 days.
- Have had known seroconversion within 6 months prior to study entry.
- Have any infection requiring treatment within 30 days prior to study entry.
- Have had a fever for 7 days in a row during the 30 days before study entry.
- Have cancer that requires chemotherapy.
- Are pregnant or breast-feeding.
- Are taking certain medications.
Locations and Contacts
Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Aaron Diamond AIDS Rsch Ctr / Rockefeller Univ, New York, New York 10021, United States
Additional Information
Click here for more information about Stavudine Click here for more information about Nevirapine Click here for more information about Indinavir sulfate Click here for more information about Lamivudine/Zidovudine Click here for more information about Hepatitis A Vaccine (Inactivated) Haga clic aquí para ver información sobre este ensayo clínico en español
Last updated: June 23, 2005
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