Comparing the Safety, Effectiveness, and Tolerability of Three Anti-HIV Drug Regimens for Treatment-Naive Patients

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00050895
• Collaborator: (none)
• Enrollment: 775
• Locations: 60
• Patients Per Site: 12.9

Study Details

Study Description

Brief Summary

With new strategies and drugs available, many different regimens exist for the treatment of HIV. The purpose of this study is to compare three different anti-HIV drug regimens as first-time treatments for HIV infection.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Lopinavir/ritonavir; Drug: Efavirenz; Drug: Stavudine; Drug: Zidovudine; Drug: Lamivudine; Drug: Tenofovir disoproxil fumarate	Phase 3

Detailed Description

Numerous treatment options are available to HIV infected patients who are antiretroviral (ARV) therapy naive, but an optimal regimen has not yet been established. This study will compare a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, a ritonavir (RTV)-enhanced protease inhibitor (PI)-based regimen, and a nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimen for the initial treatment of HIV infection.

Patients will be randomly assigned to one of three study arms. In Arm A, patients will receive lopinavir/ritonavir (LPV/r) twice daily and efavirenz (EFV) once daily before bed. Arm B patients will receive LPV/r twice daily, lamivudine (3TC) once daily, plus either stavudine extended release (d4T XR) once daily, zidovudine (ZDV) twice daily, or tenofovir disoproxil fumarate (TDF) once daily. Patients in Arm C will receive EFV once daily before bed and 3TC plus either d4T XR once daily before bed, ZDV twice daily, or TDF once daily before bed.

Study visits will occur every 4 weeks until Week 24, then every 8 weeks thereafter for a maximum of 96 weeks. Blood will be drawn at every visit and a urine sample will be collected every 8 weeks. Body measurements will be taken at Weeks 24, 48, 72, and 96. Whole body dual-energy x-ray absorptiometry (DEXA) scans will be done at Weeks 48 and 96. Patients must fast before study visits at Weeks 12, 24, 48, 72, and 96. Women in the study will have gynecological assessments every 24 weeks.

Study Design

• Study Type: Interventional
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Open-Label Comparison of Lopinavir/Ritonavir Plus Efavirenz Versus Lopinavir/Ritonavir Plus 2 NRTIs Versus Efavirenz Plus 2 NRTIs as Initial Therapy for HIV-1 Infection
• Actual Study Completion Date: Mar 1, 2006

Outcome Measures

Primary Outcome Measures

1. Time from study entry to virologic failure []

2. time from study entry to regimen completion []

Secondary Outcome Measures

1. 20 % or more loss in peripheral fat []

2. increase in lactic acid levels at least 2-4old above the upper limit of normal (ULN) []

3. 20 % or more increase in truncal fat accumulation []

4. fasting cholesterol level equal to or greater than 240 mg/dl []

5. Grade 3 or greater elevation in fasting triglyceride levels []

6. change from baseline in insulin resistance [at Weeks 24, 48 and 96]

7. change from baseline of whole-body bone density and whole-body bone mineral content [at Weeks 48 and 96]

8. time to confirmed virologic failure while on Steps I (initial randomized regimen) or II (within class substitutes for initial regimen toxicity) OR treatment-limiting toxicity on Steps I or II []

9. number of antiretroviral classes with resistance mutations at virologic failure []

10. number of missed medication doses [4 days prior]

11. change from baseline in self-reported symptoms OR occurrence of reporting an increase in symptoms [at Weeks 4, 48, 72 and 96]

12. change from baseline in body image OR occurrence of reporting body image distress [at Weeks 24, 48, 72 and 96]

13. time until treatment-limiting toxicity OR occurrence of Grades 3 or 4 toxicity []

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria for Step 1:

• HIV infected

• HIV viral load of 2000 copies/ml or greater within 60 days prior to study entry

• Willing to use acceptable means of contraception

• d4T XR, TDF, or ZDV chosen as part of an initial regimen prior to randomization to a study arm

• Coenrolled in ACTG A5152s

Exclusion Criteria for Step 1:

• On ARV therapy for 7 days or more any time prior to study entry

• NNRTIs or 3TC at any time prior to study entry

• Current peripheral neuropathy of Grade 2 or higher

• Pregnancy or breastfeeding

• Immunomodulators, vaccines, or investigational therapies within 30 days of study entry. Patients taking a stable or tapering dose of prednisone at less than 10 mg are not excluded.

• Human growth hormone within 30 days prior to study entry

• Initiation of testosterone or anabolic steroids within 30 days prior to study entry

• Certain other medications within 30 days of study entry

• Hypersensitivity to components of the study drug formulations

• Drug or alcohol use or dependence that would interfere with adherence to study requirements

• Acute therapy for serious medical illnesses requiring systemic treatment and/or hospitalization within 14 days prior to study entry

• Recent infection with drug-resistant HIV

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS	Birmingham	Alabama	United States	35924
2	USC CRS	Los Angeles	California	United States	90033-1079
3	UCLA CARE Center CRS	Los Angeles	California	United States	90095-1793
4	Stanford CRS	Palo Alto	California	United States	94305-5107
5	UC Davis Medical Center	Sacramento	California	United States	95814
6	Univ. of California Davis Med. Ctr., ACTU	Sacramento	California	United States
7	Ucsd, Avrc Crs	San Diego	California	United States	92103
8	Ucsf Aids Crs	San Francisco	California	United States	94110
9	Santa Clara Valley Med. Ctr.	San Jose	California	United States	94305-5107
10	San Mateo County AIDS Program	San Mateo	California	United States	94305-5107
11	Harbor-UCLA Med. Ctr. CRS	Torrance	California	United States	90502-2052
12	University of Colorado Hospital CRS	Aurora	Colorado	United States	80262-3706
13	Georgetown University CRS (GU CRS)	Washington	District of Columbia	United States	20007
14	Univ. of Miami AIDS CRS	Miami	Florida	United States	33136
15	The Ponce de Leon Ctr. CRS	Atlanta	Georgia	United States	30308
16	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States	96816
17	Northwestern University CRS	Chicago	Illinois	United States	60611-3015
18	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612-3806
19	Cook County Hosp. CORE Ctr.	Chicago	Illinois	United States	60612
20	Methodist Hosp. of Indiana	Indianapolis	Indiana	United States	46202-1261
21	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202-5250
22	Indiana Univ. School of Medicine, Wishard Memorial	Indianapolis	Indiana	United States	46202
23	Univ. of Iowa Healthcare, Div. of Infectious Diseases	Iowa City	Iowa	United States	52242-1201
24	IHV Baltimore Treatment CRS	Baltimore	Maryland	United States	21201
25	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
26	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
27	Bmc Actg Crs	Boston	Massachusetts	United States	02118
28	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts	United States	02215
29	Brigham and Women's Hosp. ACTG CRS	Boston	Massachusetts	United States	02215
30	SSTAR, Family Healthcare Ctr.	Fall River	Massachusetts	United States
31	University of Minnesota, ACTU	Minneapolis	Minnesota	United States	55455-0392
32	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri	United States	63108-2138
33	Washington U CRS	Saint Louis	Missouri	United States	63108-2138
34	Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.	Omaha	Nebraska	United States	68198-5130
35	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
36	Beth Israel Med. Ctr., ACTU	New York	New York	United States	10003
37	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016-6481
38	Cornell CRS	New York	New York	United States	10021
39	Columbia Univ., HIV Prevention and Treatment Medical Ctr.	New York	New York	United States	10032-3784
40	HIV Prevention & Treatment CRS	New York	New York	United States
41	Weill Med. College of Cornell Univ., The Cornell CTU	New York	New York	United States
42	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642-0001
43	AIDS Care CRS	Rochester	New York	United States
44	McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit	Rochester	New York	United States
45	Unc Aids Crs	Chapel Hill	North Carolina	United States	27514
46	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina	United States	27710
47	Wake County Health and Human Services CRS	Raleigh	North Carolina	United States
48	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	45267-0405
49	Case CRS	Cleveland	Ohio	United States	44106-5083
50	MetroHealth CRS	Cleveland	Ohio	United States	44109-1998
51	Cleveland Clinic Foundation, Div. of Medicine, Infectious Diseases	Cleveland	Ohio	United States	44109-5083
52	The Ohio State Univ. AIDS CRS	Columbus	Ohio	United States	43210-1282
53	Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.	Philadelphia	Pennsylvania	United States	19104
54	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19401
55	Pitt CRS	Pittsburgh	Pennsylvania	United States	15213-2582
56	Rhode Island Hosp.	Providence	Rhode Island	United States	02906
57	The Miriam Hosp. ACTG CRS	Providence	Rhode Island	United States	02906
58	Vanderbilt Therapeutics CRS	Nashville	Tennessee	United States	37203
59	University of Washington AIDS CRS	Seattle	Washington	United States	98104
60	Durban Adult HIV CRS	Durban	KwaZulu-Natal	South Africa

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Sharon Riddler, MD, University of Pittsburgh
• Study Chair: Richard Haubrich, MD, University of California, San Diego, Division of Infectious Diseases

Study Documents (Full-Text)

None provided.

More Information

Publications

• DiRienzo AG, DeGruttola V. Design and analysis of clinical trials with a bivariate failure time endpoint, with application to AIDS Clinical Trials Group Study A5142. Control Clin Trials. 2003 Apr;24(2):122-34.
• Saint-Marc T, Partisani M, Poizot-Martin I, Rouviere O, Bruno F, Avellaneda R, Lang JM, Gastaut JA, Touraine JL. Fat distribution evaluated by computed tomography and metabolic abnormalities in patients undergoing antiretroviral therapy: preliminary results of the LIPOCO study. AIDS. 2000 Jan 7;14(1):37-49.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00050895
• Other Study ID Numbers: A5142; 10085; ACTG A5142; A5152s; A5160s
• First Posted: Jan 1, 2003
• Last Update Posted: Nov 1, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Reverse Transcriptase Inhibitors; HIV Protease Inhibitors; Drug Therapy, Combination; Delayed Action Preparations; Treatment Naive; HIV-1
• Additional relevant MeSH terms: Infections; Ritonavir; Lopinavir; Tenofovir; Lamivudine; Zidovudine; Stavudine; Efavirenz

Study Results

No Results Posted as of Nov 1, 2021