Long-Term Assessment for Metabolic, Cardiovascular and Neurologic Problems in HIV-Infected Patients With Increased CD4 Cells Counts Following Anti-HIV Therapy

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000883
First received: November 2, 1999
Last updated: October 24, 2012
Last verified: October 2012
  Purpose

The purpose of this study is to see if there are any changes in sugar and fat levels in the blood when patients take anti-HIV therapy for many years. Another goal is to test memory and mental concentrations to determine if anti-HIV drugs protect the brain from damage caused by HIV.

(The purpose of this study has been changed from the original version.) HIV-infected patients with low CD4 cell counts are at risk for getting opportunistic (AIDS-related) infections. CD4 cells are cells of the immune system that help fight infection. Anti-HIV therapy may increase CD4 counts, which may lead to a decrease in AIDS-related infections. Problems that anti-HIV therapy is associated with include metabolic problems, neurologic problems, abnormal opportunistic infections, and cancer. Patients in ACTG 362 have been exposed to anti-HIV therapy longer than any other large group in the ACTG. These patients appear to benefit from their therapy, but also suffer problems from it. Observation of these patients should provide more information about long-term anti-HIV treatment and may detect unexpected problems.

(This study as been changed. More information about the reasons for conducting this study has been added.)


Condition Intervention
Mycobacterium Avium-intracellulare Infection
HIV Infections
Drug: Azithromycin

Study Type: Interventional
Study Design: Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Long-Term Assessment for Metabolic, Cardiovascular and Neurologic Complications In Subjects With Past CD4 Cells/mm3 Below 50 Who Increased CD4 Cells/mm3 to Above 100 on HAART

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 636
Study Start Date: October 1997
Study Completion Date: April 2007
Detailed Description:

The currently available data on clinical events in patients receiving potent antiretroviral therapy suggest that an alteration in the presentation of MAC disease may be seen and that rates of MAC disease may be reduced when patients respond to antiretroviral therapy. However, the extent of the protection and the timing of protection after initiation of therapy remain unknown. The current study should provide validated measures of immune restoration and clinical data to guide prophylaxis decisions for the many patients who are now responding to therapy after years of immune depletion. [AS PER AMENDMENT 11/16/99: The low rate of MAC in ACTG 362 patients after an average of 1 year of follow-up suggests that prophylaxis specifically for MAC disease with azithromycin is not necessary for patients who have experienced immune reconstitution. Prolonged follow-up will define durability of the antiretroviral response and the experience with opportunistic conditions, neurologic diseases, and survival, especially in those whose CD4 counts drop below 50 cells/mm3. It will also allow assessment of the levels of CD4 cell number at which vulnerability to opportunistic infection recur.] [AS PER AMENDMENT 03/18/03: During the extension of ACTG 362, serious complications of HAART have become better defined, including metabolic complications, neurologic problems, atypical opportunistic infections, and malignancies. Patients in ACTG 362 have been exposed to HAART longer than any other large group in the ACTG, and appear to benefit from and suffer complications of their therapy. Continued observation should provide estimates of expected complications and durability of long-term potent antiretroviral treatment, and may detect unanticipated problems.]

Patients are stratified at baseline for prior use of MAC into 3 groups: no prophylaxis, prior azithromycin prophylaxis, and other MAC prophylaxis. Patients are randomized to receive azithromycin (Arm I) or matching placebo (Arm II) once weekly and are followed every 8 weeks until study closure or for 18 months (72 weeks) after the last patient is enrolled. Patients who develop a drop in CD4 count below 50 cells/mm3 on 2 measurements at least 4 weeks apart are offered open-label azithromycin. [AS PER AMENDMENT 06/24/98: Patients remain on open-label azithromycin regardless of subsequent CD4 counts.] [AS PER AMENDMENT 11/16/99: The phase of Version 1.0 or Version 2.0 in which patients receive blinded-study medication is now referred to as Step I. The phase of Version 1.0 or Version 2.0 in which patients receive open-label azithromycin is now referred to as Step 2. Patients not currently on open-label azithromycin provided by the study enter Step 3 and discontinue study drugs, but remain blinded to the original treatment and are followed at 16-week intervals until study closure which will occur in April 2002 (3 years following enrollment of the last study participant). Any patient who develops a drop in CD4 count below 50 cells/mm3 on 2 measurements at least 4 weeks apart is offered open-label azithromycin. Patients currently receiving open-label azithromycin and patients from Step 3 who are initiating open-label azithromycin enter Step 4.] Patients undergo regular clinical and laboratory evaluations that include physical examinations, CD4 counts, and viral load. [AS PER AMENDMENT 11/16/99: Patients undergo clinical and laboratory evaluations every 16 weeks for 160 weeks that include physical examinations, CD4 counts, and viral load as well as neuropsychologic and cardiovascular assessments.] [AS PER AMENDMENT 01/18/01: All patients enrolled in the study are followed until April 2002.] [AS PER AMENDMENT 03/18/02: All patients currently participating in ACTG 362 are invited to continue follow up for an additional 5 years. Patients not currently receiving open-label azithromycin enter Step 5. Patients currently receiving open-label azithromycin enter Step 6, and continue to receive open-label treatment throughout the study. Any patient who enters on Step 5 and develops a drop in CD4 below 50 cells/mm3 on 2 consecutive measurements at least 4 weeks apart is offered open-label azithromycin and enters Step 6. Patients are assessed for metabolic, cardiovascular, and neurologic complications and are evaluated for opportunistic infections, CD4 counts, and viral load. Study visits occur at 32-week intervals until study closure.]

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

  • Are HIV-positive.
  • Are at least 13 years old (need consent of parent or guardian if under 18).
  • Have had an increase in CD4 cell count from less than or equal to 50 cells/mm3 to over 100 cells/mm3 on 2 separate occasions, at least 4 weeks apart. (This reflects a change in the CD4 cell count requirement.)
  • Are on anti-HIV therapy.
  • Are currently enrolled in Version 4.0 of the study.
  • (This study has been changed to include the enrollment of patients into Version 4.0 of the study.)

Exclusion Criteria

Patients will not be eligible for this study if they:

  • Are allergic to azithromycin.
  • Have had MAC disease.
  • Have a history of tuberculosis (unless successfully treated and off anti-tuberculosis drugs for over 6 months) or other mycobacterial infection requiring chemotherapy.
  • Have taken interleukin-2 (IL-2) in the past. (This study has been changed. Patients can now take IL-2 during the study.)
  • Are taking certain medications.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000883

  Show 51 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Judith Currier
Study Chair: Allen McCutchan
Study Chair: Susan Koletar
  More Information

Additional Information:
Publications:
von Reyn CF, Williams P, Becker S, Nevin T, Lederman H, Currier J. Skin test reactivity to mycobacterium avium sensitin among patients in ACTG 362. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:151 (abstract no 443)
Cohn SE, Kammann E, Williams P, Chesney MA, Currier J. Predictors of adherence to azithromycin prophylaxis for prevention of mycobacterium avium complex (MAC) disease. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:151 (abstract no 444)
Lederman HM, von Reyn CF, Becker S, Williams P, Currier J. Improved immunologic function correlates with CD4 rise after highly active anti-retroviral therapy (HAART). Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:129 (abstract no 326)

ClinicalTrials.gov Identifier: NCT00000883     History of Changes
Other Study ID Numbers: ACTG 362
Study First Received: November 2, 1999
Last Updated: October 24, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS-Related Opportunistic Infections
Mycobacterium avium-intracellulare Infection
Antibiotics, Macrolide
Acquired Immunodeficiency Syndrome
Azithromycin
CD4 Lymphocyte Count
Anti-HIV Agents

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Mycobacterium Infections
Mycobacterium avium-intracellulare Infection
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Mycobacterium Infections, Atypical
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014