A Randomized, Double-Blind Phase II/III Trial of Monotherapy vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00000625
• Collaborator: Bristol-Myers Squibb (Industry), Glaxo Wellcome (Industry)
• Enrollment: 2,100
• Locations: 58
• Patients Per Site: 36.2

Study Details

Study Description

Brief Summary

To determine the efficacy and safety of zidovudine ( AZT ) versus didanosine ( ddI ), AZT plus ddI, and AZT plus zalcitabine ( ddC ) in preventing disease progression in HIV-infected patients with CD4 counts of 200-500 cells/mm3.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Zidovudine; Drug: Zalcitabine; Drug: Didanosine	Phase 2

Detailed Description

Patients are randomized to receive AZT alone, AZT and ddI, AZT and ddC, or ddI alone for at least 2 years. Patients who develop AIDS or whose CD4 count falls to 50 percent or less of baseline are crossed over to another treatment arm.

PER AMENDMENT 4/5/95: Study treatment will be available until 10/31/95 at the latest for patients still taking study medications on 4/30/95, so that follow-up trials may be completed and approved.

Study Design

• Study Type: Interventional
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind Phase II/III Trial of Monotherapy vs. Combination Therapy With Nucleoside Analogs in HIV-Infected Persons With CD4 Cells of 200-500/mm3
• Actual Study Completion Date: Nov 1, 1995

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

Concurrent Medication:

Allowed:

• PCP prophylaxis, M. tuberculosis prophylaxis, short courses of acyclovir, chronic suppressive acyclovir, pneumovax or Hib vaccine, antibiotics, rEPO and G-CSF for grade 3 or worse anemia and neutropenia, systemic corticosteroids for < 21 days, regularly prescribed medications, and vitamins or herbal therapies.

Patients must have:

• HIV infection without AIDS with CD4 200-500 cells/mm3.

PER AMENDMENT 4/5/95:

• Patients must have remained on ACTG 175 study treatment through 4/30/95 and meet toxicity management criteria for continuing treatment. Subjects taking ACTG 175 crossover treatment are eligible.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions are excluded:

• Current AIDS-related condition other than minimal KS, grade 2 or worse peripheral neuropathy, and malignancy requiring systemic therapy.

Concurrent Medication:

Excluded:

• Other anti-HIV drugs, biologic response modifiers other than rEPO and G-CSF, systemic cytotoxic chemotherapy, chronic systemic corticosteroids, or any drug that affects AZT glucuronidation or clearance.

Concurrent Treatment:

Excluded:

• Radiotherapy other than limited local therapy to skin.

Patients with the following prior conditions are excluded:

• AIDS-related condition other than minimal KS; intolerance to AZT, ddI, or ddC at study doses; and acute or chronic pancreatitis.

Prior Medication:

Excluded:

• Acute therapy for an infection or other medical illness within the past 14 days.

Current alcohol abuse.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS	Birmingham	Alabama	United States	35294
2	USC CRS	Los Angeles	California	United States	90033
3	UCLA CARE Center CRS	Los Angeles	California	United States	90095
4	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California	United States	94609
5	Stanford CRS	Palo Alto	California	United States	94305
6	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California	United States	92093
7	Ucsd, Avrc Crs	San Diego	California	United States
8	Ucsf Aids Crs	San Francisco	California	United States
9	Santa Clara Valley Med. Ctr.	San Jose	California	United States	95128
10	San Mateo County AIDS Program	San Mateo	California	United States	94305
11	Harbor-UCLA Med. Ctr. CRS	Torrance	California	United States	90502
12	University of Colorado Hospital CRS	Aurora	Colorado	United States	80262
13	Howard University Hosp., Div. of Infectious Diseases, ACTU	Washington	District of Columbia	United States	20059
14	Univ. of Miami AIDS CRS	Miami	Florida	United States	33136
15	Emory Univ. Hemophilia Program Office	Atlanta	Georgia	United States	30365
16	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States	96816
17	Northwestern University CRS	Chicago	Illinois	United States	60611
18	Cook County Hosp. CORE Ctr.	Chicago	Illinois	United States	60612
19	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
20	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
21	Methodist Hosp. of Indiana	Indianapolis	Indiana	United States	46202
22	Univ. of Iowa Healthcare, Div. of Infectious Diseases	Iowa City	Iowa	United States	52242
23	Tulane Hemophilia Treatment Ctr.	New Orleans	Louisiana	United States	70112
24	Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU	New Orleans	Louisiana	United States	70112
25	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana	United States	70112
26	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
27	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
28	Brigham and Women's Hosp., Div. of Infectious Disease	Boston	Massachusetts	United States	02115
29	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts	United States	02115
30	Bmc Actg Crs	Boston	Massachusetts	United States	02118
31	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts	United States	02215
32	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts	United States	02215
33	Hennepin County Med. Ctr., Div. of Infectious Diseases	Minneapolis	Minnesota	United States	55455
34	University of Minnesota, ACTU	Minneapolis	Minnesota	United States
35	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri	United States	63112
36	Washington U CRS	Saint Louis	Missouri	United States
37	Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.	Omaha	Nebraska	United States
38	NJ Med. School CRS	Newark	New Jersey	United States
39	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
40	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York	United States	10003
41	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
42	Cornell University A2201	New York	New York	United States	10021
43	Memorial Sloan-Kettering Cancer Ctr.	New York	New York	United States	10021
44	NYU Med. Ctr., Dept. of Medicine	New York	New York	United States
45	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
46	Unc Aids Crs	Chapel Hill	North Carolina	United States	27599
47	Carolinas HealthCare System, Carolinas Med. Ctr.	Charlotte	North Carolina	United States	28203
48	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina	United States	27710
49	Regional Center for Infectious Disease, Wendover Medical Center CRS	Greensboro	North Carolina	United States	27401
50	Wake County Health and Human Services CRS	Raleigh	North Carolina	United States	27610
51	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	45267
52	Case CRS	Cleveland	Ohio	United States	44106
53	MetroHealth CRS	Cleveland	Ohio	United States
54	The Ohio State Univ. AIDS CRS	Columbus	Ohio	United States	43210
55	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19104
56	University of Washington AIDS CRS	Seattle	Washington	United States	98122
57	Puerto Rico-AIDS CRS	San Juan		Puerto Rico
58	Mbeya Med. Research Program, Mbeya Referral Hosp. CRS	Mbeya		Tanzania

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Bristol-Myers Squibb
• Glaxo Wellcome

Investigators

• Study Chair: Katzenstein D,
• Study Chair: Hammer S,

Study Documents (Full-Text)

None provided.

More Information

Publications

• Currier JS, Spino C, Grimes J, Wofsy CB, Katzenstein DA, Hughes MD, Hammer SM, Cotton DJ. Differences between women and men in adverse events and CD4+ responses to nucleoside analogue therapy for HIV infection. The Aids Clinical Trials Group 175 Team. J Acquir Immune Defic Syndr. 2000 Aug 1;24(4):316-24.
• Fiscus SA, Hughes MD, Lathey JL, Pi T, Jackson B, Rasheed S, Elbeik T, Reichman R, Japour A, Byington R, Scott W, Griffith BP, Katzenstein DA, Hammer SM. Changes in virologic markers as predictors of CD4 cell decline and progression of disease in human immunodeficiency virus type 1-infected adults treated with nucleosides. AIDS Clinical Trials Group Protocol 175 Team. J Infect Dis. 1998 Mar;177(3):625-33.
• Hammer SM, Katzenstein DA, Hughes MD, Gundacker H, Schooley RT, Haubrich RH, Henry WK, Lederman MM, Phair JP, Niu M, Hirsch MS, Merigan TC. A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter. AIDS Clinical Trials Group Study 175 Study Team. N Engl J Med. 1996 Oct 10;335(15):1081-90.
• Havlir DV, Richman DD. Viral dynamics of HIV: implications for drug development and therapeutic strategies. Ann Intern Med. 1996 Jun 1;124(11):984-94. Review.
• Justice AC, Holmes W, Gifford AL, Rabeneck L, Zackin R, Sinclair G, Weissman S, Neidig J, Marcus C, Chesney M, Cohn SE, Wu AW; Adult AIDS Clinical Trials Unit Outcomes Committee. Development and validation of a self-completed HIV symptom index. J Clin Epidemiol. 2001 Dec;54 Suppl 1:S77-90.
• Kastrissios H, Suárez JR, Katzenstein D, Girard P, Sheiner LB, Blaschke TF. Characterizing patterns of drug-taking behavior with a multiple drug regimen in an AIDS clinical trial. AIDS. 1998 Dec 3;12(17):2295-303.
• Katzenstein DA, Hammer SM, Hughes MD, Gundacker H, Jackson JB, Fiscus S, Rasheed S, Elbeik T, Reichman R, Japour A, Merigan TC, Hirsch MS. The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. AIDS Clinical Trials Group Study 175 Virology Study Team. N Engl J Med. 1996 Oct 10;335(15):1091-8. Erratum in: N Engl J Med 1997 Oct 9;337(15):1097.
• Katzenstein DA, Hughes MD, Albrecht M, Liou SH, Murphy R, Balfour H, Para M, Hammer S; ACTG 302 Study Team. Virologic and CD4 cell response to zidovudine or zidovudine and lamivudine following didanosine treatment of human immunodeficiency virus infection. AIDS Res Hum Retroviruses. 2001 Feb 10;17(3):203-10.
• Lathey JL, Hughes MD, Fiscus SA, Pi T, Jackson JB, Rasheed S, Elbeik T, Reichman R, Japour A, D'Aquila RT, Scott W, Griffith BP, Hammer SM, Katzenstein DA. Variability and prognostic values of virologic and CD4 cell measures in human immunodeficiency virus type 1-infected patients with 200-500 CD4 cells/mm(3) (ACTG 175). AIDS Clinical Trials Group Protocol 175 Team. J Infect Dis. 1998 Mar;177(3):617-24.
• Simpson DM, Katzenstein DA, Hughes MD, Hammer SM, Williamson DL, Jiang Q, Pi JT. Neuromuscular function in HIV infection: analysis of a placebo-controlled combination antiretroviral trial. AIDS Clinical Group 175/801 Study Team. AIDS. 1998 Dec 24;12(18):2425-32.
• Zidovudine, didanosine, and zalcitabine in the treatment of HIV infection: meta-analyses of the randomised evidence. HIV Trialists' Collaborative Group. Lancet. 1999 Jun 12;353(9169):2014-25.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00000625
• Other Study ID Numbers: ACTG 175; 11150
• First Posted: Aug 31, 2001
• Last Update Posted: Nov 2, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Zalcitabine; Didanosine; Drug Therapy, Combination; AIDS-Related Complex; Antiviral Agents; Zidovudine
• Additional relevant MeSH terms: HIV Infections; Zidovudine; Didanosine; Zalcitabine

Study Results

No Results Posted as of Nov 2, 2021