Safety of and Immune Response to Cyclosporine A in Combination With Abacavir Sulfate, Lamivudine, and Zidovudine and Lopinavir/Ritonavir in Adults With Acute HIV Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00084149
First received: June 7, 2004
Last updated: July 26, 2013
Last verified: July 2013

June 7, 2004
July 26, 2013
February 2004
January 2008   (final data collection date for primary outcome measure)
Levels of proviral DNA in PBMC [ Time Frame: At 48 weeks after the start of treatment ] [ Designated as safety issue: No ]
Levels of proviral DNA in PBMC measured at 48 weeks after the start of treatment
Complete list of historical versions of study NCT00084149 on ClinicalTrials.gov Archive Site
  • Adverse events related to study medication [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Proviral DNA levels [ Time Frame: At Weeks 12 and 24 ] [ Designated as safety issue: No ]
  • Decay of proviral DNA [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • HIV-1 viral load levels [ Time Frame: At Weeks 24 and 48 ] [ Designated as safety issue: No ]
  • Percent of patients with viral loads less than 50 copies/ml [ Time Frame: Througout study ] [ Designated as safety issue: No ]
  • Percent of patients with viral loads less than 5 copies/ml [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • T cell levels [ Time Frame: At Weeks 2, 4, 8, 12, 24, and 48 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
Safety of and Immune Response to Cyclosporine A in Combination With Abacavir Sulfate, Lamivudine, and Zidovudine and Lopinavir/Ritonavir in Adults With Acute HIV Infection
A Randomized Phase II Study of the Safety, Immunologic, and Virologic Effects of Cyclosporine A in Conjunction With Trizivir(R) and Kaletra(R) Versus Trizivir(R) and Kaletra(R) Alone During Primary HIV-1 Infection

Cyclosporine A (CsA) is a common long-term treatment used to inhibit the immune response in transplant patients who receive donor organs. CsA may also help people with HIV. The purpose of this study is to determine the safety of and immune response to CsA when given with abacavir sulfate, lamivudine, and zidovudine (ABC/3TC/AZT) and lopinavir/ritonavir (LPV/r) to HIV infected adults in the early stages of infection.

Study hypothesis: The combination of CsA and LPV/r given to acutely infected individuals will result in lower levels of proviral DNA and latent infectious virus at 48 weeks compared to acute infected individuals treated with LPV/r alone.

During the early stages of HIV infection, HIV replicates unchecked, massive numbers of CD4 T cells are infected and destroyed, and other CD4 cells become infected but enter a latent phase. This latent pool of infected CD4 cells poses a difficult challenge in eliminating HIV infection during the early stages of infection because the cells persist for long periods, even with highly active effective antiretroviral therapy, and may later become active.

CsA is popularly used as a lifelong immunosuppressant for organ transplant patients. CsA inhibits cellular activation, including CD4 cell activation and proliferation. By reducing CD4 cell activation during acute HIV infection, fewer CD4 cells may be infected and die; more importantly, there may be fewer latent cells with the potential to become active later in the disease. However, CsA has many potential toxic effects, including renal damage, and may affect neurologic, endocrine, and hepatic organ systems.

In a previous small study of adults with acute HIV infection, a short 8-week course of CsA was well tolerated, and it is thought that a 4-week course of CsA may result in substantial reduction in both viral load and T cell activation, outweighing any potential toxic effects sustained during the one month treatment. This study will evaluate the safety of and immune response to a 4-week course of CsA with ABC/3TC/AZT and LPV/r compared to ABC/3TC/AZT and LPV/r alone in patients with acute HIV infection.

This 48-week study will randomly assign patients to one of two arms. During the first 4 weeks of the study, Arm A will receive one tablet of ABC/3TC/AZT twice daily, 3 capsules or 2 tablets of LPV/r twice daily, and liquid CsA (dose determined by weight) twice daily. At Week 5, Arm A patients will stop CsA but continue both ABC/3TC/AZT and LPV/r. Arm B will receive one tablet of ABC/3TC/AZT twice daily and 3 capsules or 2 tablets of LPV/r twice daily for all 48 weeks. On a case-by-case basis, an investigator may wish to prescribe ABC/3TC rather than ABC/3TC/AZT at initial therapy. Participants with ABC hypersensitivity will be given 3TC/AZT instead of ABC/3TC/AZT.

A complete physical exam and medical history assessment will occur at study entry and at Week 48. Study visits will occur every week until Week 4, then every 4 weeks until the end of the study. Blood and urine collection and clinical assessments will occur at each study visit. Additionally, patients in Arm A only will undergo CsA level monitoring at Day 3 and Weeks 1, 2, and 3; CsA dosage may be adjusted as necessary.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Abacavir sulfate, Lamivudine, and Zidovudine
    antiretroviral therapy
  • Drug: Lopinavir/Ritonavir
    antiretroviral therapy
  • Experimental: A
    Arm A will receive one tablet of ABC/3TC/AZT twice daily, 3 capsules or 2 tablets of LPV/r twice daily, and liquid CsA (dose determined by weight) twice daily. At Week 5, Arm A patients will stop CsA but continue both ABC/3TC/AZT and LPV/r.
    Interventions:
    • Drug: Abacavir sulfate, Lamivudine, and Zidovudine
    • Drug: Lopinavir/Ritonavir
  • Experimental: B
    Arm B will receive one tablet of ABC/3TC/AZT twice daily and 3 capsules or 2 tablets of LPV/r twice daily for all 48 weeks
    Interventions:
    • Drug: Abacavir sulfate, Lamivudine, and Zidovudine
    • Drug: Lopinavir/Ritonavir

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
January 2008
January 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Acute HIV infection with HIV viral load of more than 50,000 copies/ml AND either negative ELISA OR Western blot with 5 bands or less within 4 weeks prior to study entry
  • Hepatitis B surface antigen negative within 12 weeks prior to study entry
  • Hepatitis C antibody negative within 12 weeks prior to study entry
  • Willing to use acceptable methods of contraception

Exclusion Criteria:

  • Prior antiretroviral therapy. A patient who has undergone Post Exposure Prophylaxis (PEP) taken at least 6 months prior to study entry is not excluded.
  • Allergy or hypersensitivity to any study medications or their components
  • Require certain medications, including those that may alter CsA levels or cause renal dysfunction. More information on this criterion can be found in the protocol.
  • Any medical or psychiatric condition, including alcohol or drug abuse, that may interfere with adherence to study requirements
  • Weight less than 88 lbs (40 kg)
  • Uncontrolled hypertension
  • History of pancreatitis
  • History of cancer. Participants with cancer in remission who have not had treatment for at least 3 years may be eligible for this study.
  • Pregnancy or breastfeeding
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00084149
AIN501/A5216, 10023, AIEDRP AIN501/ACTG A5216, AIEDRP AIN501, ACTG A5216
Not Provided
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Allergy and Infectious Diseases (NIAID)
Not Provided
Study Chair: Martin Markowitz, MD Aaron Diamond AIDS Research Center
Study Chair: Susan Little, MD Department of Medicine, University of California at San Diego
National Institute of Allergy and Infectious Diseases (NIAID)
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP