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.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Abacavir sulfate, Lamivudine, and Zidovudine  Drug: Lopinavir/Ritonavir	Phase II

Further Study Details: 

Primary Outcomes: Levels of proviral DNA in PBMC measured at 48 weeks after the start of treatment
Expected Total Enrollment:  50

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 1 will receive one tablet of ABC/3TC/AZT twice daily, 3 capsules of LPV/r twice daily, and liquid CsA (dose determined by weight) twice daily. At Week 5, Arm 1 patients will stop CsA but continue both ABC/3TC/AZT and LPV/r. Arm 2 will receive one tablet of ABC/3TC/AZT twice daily and 3 capsules of LPV/r twice daily for all 48 weeks.

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Acute HIV infection with HIV viral load of more than 50,000 copies/ml AND either negative ELISA OR Western blot with 3 bands or less
• 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
• 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

Alabama
      University of Alabama-Birmingham, Birmingham,  Alabama,  35294-2050,  United States; Not yet recruiting
California
      University of California-San Diego, San Diego,  California,  92103,  United States; Recruiting
      San Francisco General Hospital, San Francisco,  California,  94110,  United States; Recruiting
      University of California-San Francisco, San Francisco,  California,  94110,  United States; Recruiting
      Harbor-UCLA, Culver City,  California,  90230,  United States; Recruiting
Florida
      University of Miami, Miami,  Florida,  33136-1013,  United States; Recruiting
Minnesota
      University of Minnesota, Minneapolis,  Minnesota,  55455-0392,  United States; Recruiting
New York
      Aaron Diamond AIDS Research Center at Rockefeller, New York,  New York,  10021,  United States; Recruiting
      Beth Israel Medical Center, New York,  New York,  10003,  United States; Recruiting
      NYU/Bellevue, New York,  New York,  10016-6481,  United States; Recruiting
      SUNY-Downstate Medical Center, Brooklyn,  New York,  11023,  United States; Recruiting
Ohio
      Case Western Reserve University, Cleveland,  Ohio,  44106-5083,  United States; Recruiting
      University of Cincinnati, Cincinnati,  Ohio,  45267-0405,  United States; Recruiting

Study chairs or principal investigators

Martin Markowitz, MD,  Study Chair,  Aaron Diamond AIDS Research Center   
Susan Little, MD,  Study Chair,  University of California at San Diego, Department of Medicine   

Study ID Numbers:  AIEDRP AIN501/ACTG A5216; AIEDRP AIN501; ACTG A5216
Record last reviewed:  April 2005
Last Updated:  April 7, 2005
Record first received:  June 7, 2004
ClinicalTrials.gov Identifier:  NCT00084149
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08