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

October 24, 2012 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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

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.)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.]

Study Type

Interventional

Enrollment

636

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Univ of Alabama at Birmingham
    • California
      • Los Angeles, California, United States, 900331079
        • Univ of Southern California / LA County USC Med Ctr
      • Menlo Park, California, United States, 94025
        • Willow Clinic
      • San Diego, California, United States, 921036325
        • Univ of California / San Diego Treatment Ctr
      • San Francisco, California, United States, 94115
        • Stanford at Kaiser / Kaiser Permanente Med Ctr
      • San Francisco, California, United States, 941102859
        • San Francisco Gen Hosp
      • San Jose, California, United States, 951282699
        • Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
      • Stanford, California, United States, 943055107
        • San Mateo AIDS Program / Stanford Univ
      • Stanford, California, United States, 943055107
        • Stanford Univ Med Ctr
      • Torrance, California, United States, 90502
        • Harbor UCLA Med Ctr
    • Colorado
      • Denver, Colorado, United States, 80262
        • Univ of Colorado Health Sciences Ctr
    • District of Columbia
      • Washington, District of Columbia, United States, 20059
        • Howard Univ
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory Univ
      • Atlanta, Georgia, United States, 303652225
        • Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr
    • Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Univ of Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Queens Med Ctr
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Univ Med School
      • Chicago, Illinois, United States, 60612
        • Rush Presbyterian - Saint Luke's Med Ctr
      • Chicago, Illinois, United States, 60612
        • Cook County Hosp
      • Chicago, Illinois, United States, 60640
        • Louis A Weiss Memorial Hosp
    • Indiana
      • Indianapolis, Indiana, United States, 462025250
        • Indiana Univ Hosp
      • Indianapolis, Indiana, United States, 46202
        • Methodist Hosp of Indiana / Life Care Clinic
      • Indianapolis, Indiana, United States, 46202
        • Division of Inf Diseases/ Indiana Univ Hosp
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Charity Hosp / Tulane Univ Med School
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Hosp
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Harvard (Massachusetts Gen Hosp)
      • Boston, Massachusetts, United States, 02118
        • Boston Med Ctr
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess - West Campus
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Med Ctr
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Univ of Minnesota
    • Missouri
      • St Louis, Missouri, United States, 63112
        • St Louis Regional Hosp / St Louis Regional Med Ctr
    • Nebraska
      • Omaha, Nebraska, United States, 681985130
        • Univ of Nebraska Med Ctr
    • New York
      • Buffalo, New York, United States, 14215
        • SUNY / Erie County Med Ctr at Buffalo
      • New York, New York, United States, 10003
        • Beth Israel Med Ctr
      • New York, New York, United States, 10021
        • Cornell Univ Med Ctr
      • New York, New York, United States, 10016
        • Bellevue Hosp / New York Univ Med Ctr
      • New York, New York, United States, 10021
        • Mem Sloan - Kettering Cancer Ctr
      • New York, New York, United States, 10029
        • Mount Sinai Med Ctr
      • Rochester, New York, United States, 14642
        • Univ of Rochester Medical Center
      • Rochester, New York, United States, 14642
        • Community Health Network Inc
    • North Carolina
      • Chapel Hill, North Carolina, United States, 275997215
        • Univ of North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Univ Med Ctr
    • Ohio
      • Cincinnati, Ohio, United States, 452670405
        • Univ of Cincinnati
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve Univ
      • Columbus, Ohio, United States, 432101228
        • Ohio State Univ Hosp Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Univ of Pennsylvania at Philadelphia
      • Pittsburgh, Pennsylvania, United States, 15213
        • Univ of Pittsburgh Med Ctr
    • South Carolina
      • West Columbia, South Carolina, United States, 29169
        • Julio Arroyo
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr
    • Texas
      • Galveston, Texas, United States, 775550435
        • Univ of Texas Galveston
    • Washington
      • Seattle, Washington, United States, 981224304
        • Univ of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Masking: DOUBLE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Allen McCutchan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 1997

Study Completion (ACTUAL)

April 1, 2007

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (ESTIMATE)

August 31, 2001

Study Record Updates

Last Update Posted (ESTIMATE)

October 25, 2012

Last Update Submitted That Met QC Criteria

October 24, 2012

Last Verified

October 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 362

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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