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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000883

Collaborator

(none)

636

Enrollment

Locations

114

Duration (Months)

12.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.)

Condition or Disease	Intervention/Treatment	Phase
Mycobacterium Avium-intracellulare Infection HIV Infections	Drug: Azithromycin	N/A

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 Design

Study Type:

Interventional

Masking:

Double

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

Study Start Date :

Oct 1, 1997

Actual Study Completion Date :

Apr 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Univ of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Univ of Southern California / LA County USC Med Ctr	Los Angeles	California	United States	900331079
3	Willow Clinic	Menlo Park	California	United States	94025
4	Univ of California / San Diego Treatment Ctr	San Diego	California	United States	921036325
5	San Francisco Gen Hosp	San Francisco	California	United States	941102859
6	Stanford at Kaiser / Kaiser Permanente Med Ctr	San Francisco	California	United States	94115
7	Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium	San Jose	California	United States	951282699
8	San Mateo AIDS Program / Stanford Univ	Stanford	California	United States	943055107
9	Stanford Univ Med Ctr	Stanford	California	United States	943055107
10	Harbor UCLA Med Ctr	Torrance	California	United States	90502
11	Univ of Colorado Health Sciences Ctr	Denver	Colorado	United States	80262
12	Howard Univ	Washington	District of Columbia	United States	20059
13	Emory Univ	Atlanta	Georgia	United States	30308
14	Emory Hemo Comp Evaluation Clinic / East TN Comp Hemo Ctr	Atlanta	Georgia	United States	303652225
15	Queens Med Ctr	Honolulu	Hawaii	United States	96816
16	Univ of Hawaii	Honolulu	Hawaii	United States	96816
17	Northwestern Univ Med School	Chicago	Illinois	United States	60611
18	Cook County Hosp	Chicago	Illinois	United States	60612
19	Rush Presbyterian - Saint Luke's Med Ctr	Chicago	Illinois	United States	60612
20	Louis A Weiss Memorial Hosp	Chicago	Illinois	United States	60640
21	Indiana Univ Hosp	Indianapolis	Indiana	United States	462025250
22	Division of Inf Diseases/ Indiana Univ Hosp	Indianapolis	Indiana	United States	46202
23	Methodist Hosp of Indiana / Life Care Clinic	Indianapolis	Indiana	United States	46202
24	Charity Hosp / Tulane Univ Med School	New Orleans	Louisiana	United States	70112
25	Johns Hopkins Hosp	Baltimore	Maryland	United States	21287
26	Harvard (Massachusetts Gen Hosp)	Boston	Massachusetts	United States	02114
27	Boston Med Ctr	Boston	Massachusetts	United States	02118
28	Beth Israel Deaconess - West Campus	Boston	Massachusetts	United States	02215
29	Beth Israel Deaconess Med Ctr	Boston	Massachusetts	United States	02215
30	Univ of Minnesota	Minneapolis	Minnesota	United States	55455
31	St Louis Regional Hosp / St Louis Regional Med Ctr	St Louis	Missouri	United States	63112
32	Univ of Nebraska Med Ctr	Omaha	Nebraska	United States	681985130
33	SUNY / Erie County Med Ctr at Buffalo	Buffalo	New York	United States	14215
34	Beth Israel Med Ctr	New York	New York	United States	10003
35	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
36	Cornell Univ Med Ctr	New York	New York	United States	10021
37	Mem Sloan - Kettering Cancer Ctr	New York	New York	United States	10021
38	Mount Sinai Med Ctr	New York	New York	United States	10029
39	Community Health Network Inc	Rochester	New York	United States	14642
40	Univ of Rochester Medical Center	Rochester	New York	United States	14642
41	Univ of North Carolina	Chapel Hill	North Carolina	United States	275997215
42	Duke Univ Med Ctr	Durham	North Carolina	United States	27710
43	Univ of Cincinnati	Cincinnati	Ohio	United States	452670405
44	Case Western Reserve Univ	Cleveland	Ohio	United States	44106
45	Ohio State Univ Hosp Clinic	Columbus	Ohio	United States	432101228
46	Univ of Pennsylvania at Philadelphia	Philadelphia	Pennsylvania	United States	19104
47	Univ of Pittsburgh Med Ctr	Pittsburgh	Pennsylvania	United States	15213
48	Julio Arroyo	West Columbia	South Carolina	United States	29169
49	Univ of Tennessee / E Tennessee Comprehensive Hemophilia Ctr	Knoxville	Tennessee	United States	37920
50	Univ of Texas Galveston	Galveston	Texas	United States	775550435
51	Univ of Washington	Seattle	Washington	United States	981224304