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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000883
• Other study ID #: ACTG 362
• Status: Completed
• Phase: N/A
• First received: November 2, 1999
• Last updated: October 24, 2012
• Start date: October 1997
• Est. completion date: April 2007

Study information

• Verified date: October 2012
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.)

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.]

Recruitment information / eligibility

• Status: Completed
• Enrollment: 636
• Est. completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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 Design

Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• Infection
• Mycobacterium Avium-intracellulare Infection
• Mycobacterium Infections

Intervention

Drug:
• Azithromycin

Locations

Country	Name	City	State
United States	Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr	Atlanta	Georgia
United States	Emory Univ	Atlanta	Georgia
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	Univ of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deaconess - West Campus	Boston	Massachusetts
United States	Beth Israel Deaconess Med Ctr	Boston	Massachusetts
United States	Boston Med Ctr	Boston	Massachusetts
United States	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts
United States	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Cook County Hosp	Chicago	Illinois
United States	Louis A Weiss Memorial Hosp	Chicago	Illinois
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois
United States	Univ of Cincinnati	Cincinnati	Ohio
United States	Case Western Reserve Univ	Cleveland	Ohio
United States	Ohio State Univ Hosp Clinic	Columbus	Ohio
United States	Univ of Colorado Health Sciences Ctr	Denver	Colorado
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	Univ of Texas Galveston	Galveston	Texas
United States	Queens Med Ctr	Honolulu	Hawaii
United States	Univ of Hawaii	Honolulu	Hawaii
United States	Division of Inf Diseases/ Indiana Univ Hosp	Indianapolis	Indiana
United States	Indiana Univ Hosp	Indianapolis	Indiana
United States	Methodist Hosp of Indiana / Life Care Clinic	Indianapolis	Indiana
United States	Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr	Knoxville	Tennessee
United States	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California
United States	Willow Clinic	Menlo Park	California
United States	Univ of Minnesota	Minneapolis	Minnesota
United States	Charity Hosp / Tulane Univ Med School	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr	New York	New York
United States	Cornell Univ Med Ctr	New York	New York
United States	Mem Sloan - Kettering Cancer Ctr	New York	New York
United States	Mount Sinai Med Ctr	New York	New York
United States	Univ of Nebraska Med Ctr	Omaha	Nebraska
United States	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania
United States	Univ of Pittsburgh Med Ctr	Pittsburgh	Pennsylvania
United States	Community Health Network Inc	Rochester	New York
United States	Univ of Rochester Medical Center	Rochester	New York
United States	Univ of California / San Diego Treatment Ctr	San Diego	California
United States	San Francisco Gen Hosp	San Francisco	California
United States	Stanford at Kaiser / Kaiser Permanente Med Ctr	San Francisco	California
United States	Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium	San Jose	California
United States	Univ of Washington	Seattle	Washington
United States	St Louis Regional Hosp / St Louis Regional Med Ctr	St Louis	Missouri
United States	San Mateo AIDS Program / Stanford Univ	Stanford	California
United States	Stanford Univ Med Ctr	Stanford	California
United States	Harbor UCLA Med Ctr	Torrance	California
United States	Howard Univ	Washington	District of Columbia
United States	Julio Arroyo	West Columbia	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (5)

Cohn SE, Jiang H, McCutchan JA, Koletar SL, Murphy RL, Robertson KR, de St Maurice AM, Currier JS, Williams PL. Association of ongoing drug and alcohol use with non-adherence to antiretroviral therapy and higher risk of AIDS and death: results from ACTG 3 — View Citation

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)

Currier JS, Williams PL, Koletar SL, Cohn SE, Murphy RL, Heald AE, Hafner R, Bassily EL, Lederman HM, Knirsch C, Benson CA, Valdez H, Aberg JA, McCutchan JA. Discontinuation of Mycobacterium avium complex prophylaxis in patients with antiretroviral therapy-induced increases in CD4+ cell count. A randomized, double-blind, placebo-controlled trial. AIDS Clinical Trials Group 362 Study Team. Ann Intern Med. 2000 Oct 3;133(7):493-503. — View Citation

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)

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)

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