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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00050895
• Other study ID #: A5142
• Secondary ID: 10085ACTG A5142A
• Status: Completed
• Phase: Phase 3
• Est. completion date: March 2006

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 775
• Est. completion date: March 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV Infections
• Infections

Intervention

Drug:
• Lopinavir/ritonavir

• Efavirenz

• Stavudine

• Zidovudine

• Lamivudine

• Tenofovir disoproxil fumarate

Locations

Country	Name	City	State
South Africa	Durban Adult HIV CRS	Durban	KwaZulu-Natal
United States	The Ponce de Leon Ctr. CRS	Atlanta	Georgia
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	IHV Baltimore Treatment CRS	Baltimore	Maryland
United States	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland
United States	Alabama Therapeutics CRS	Birmingham	Alabama
United States	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts
United States	Bmc Actg Crs	Boston	Massachusetts
United States	Brigham and Women's Hosp. ACTG CRS	Boston	Massachusetts
United States	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts
United States	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York
United States	Unc Aids Crs	Chapel Hill	North Carolina
United States	Cook County Hosp. CORE Ctr.	Chicago	Illinois
United States	Northwestern University CRS	Chicago	Illinois
United States	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois
United States	Univ. of Cincinnati CRS	Cincinnati	Ohio
United States	Case CRS	Cleveland	Ohio
United States	Cleveland Clinic Foundation, Div. of Medicine, Infectious Diseases	Cleveland	Ohio
United States	MetroHealth CRS	Cleveland	Ohio
United States	The Ohio State Univ. AIDS CRS	Columbus	Ohio
United States	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina
United States	SSTAR, Family Healthcare Ctr.	Fall River	Massachusetts
United States	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii
United States	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana
United States	Indiana Univ. School of Medicine, Wishard Memorial	Indianapolis	Indiana
United States	Methodist Hosp. of Indiana	Indianapolis	Indiana
United States	Univ. of Iowa Healthcare, Div. of Infectious Diseases	Iowa City	Iowa
United States	UCLA CARE Center CRS	Los Angeles	California
United States	USC CRS	Los Angeles	California
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	University of Minnesota, ACTU	Minneapolis	Minnesota
United States	Vanderbilt Therapeutics CRS	Nashville	Tennessee
United States	Beth Israel Med. Ctr., ACTU	New York	New York
United States	Columbia Univ., HIV Prevention and Treatment Medical Ctr.	New York	New York
United States	Cornell CRS	New York	New York
United States	HIV Prevention & Treatment CRS	New York	New York
United States	NY Univ. HIV/AIDS CRS	New York	New York
United States	Weill Med. College of Cornell Univ., The Cornell CTU	New York	New York
United States	Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.	Omaha	Nebraska
United States	Stanford CRS	Palo Alto	California
United States	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania
United States	Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.	Philadelphia	Pennsylvania
United States	Pitt CRS	Pittsburgh	Pennsylvania
United States	Rhode Island Hosp.	Providence	Rhode Island
United States	The Miriam Hosp. ACTG CRS	Providence	Rhode Island
United States	Wake County Health and Human Services CRS	Raleigh	North Carolina
United States	AIDS Care CRS	Rochester	New York
United States	McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit	Rochester	New York
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	UC Davis Medical Center	Sacramento	California
United States	Univ. of California Davis Med. Ctr., ACTU	Sacramento	California
United States	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri
United States	Washington U CRS	Saint Louis	Missouri
United States	Ucsd, Avrc Crs	San Diego	California
United States	Ucsf Aids Crs	San Francisco	California
United States	Santa Clara Valley Med. Ctr.	San Jose	California
United States	San Mateo County AIDS Program	San Mateo	California
United States	University of Washington AIDS CRS	Seattle	Washington
United States	Harbor-UCLA Med. Ctr. CRS	Torrance	California
United States	Georgetown University CRS (GU CRS)	Washington	District of Columbia

Sponsors (1)

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

Countries where clinical trial is conducted

United States,  South Africa, 

References & Publications (6)

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. — View Citation

Gazzard B, Balkin A, Hill A. Analysis of neuropsychiatric adverse events during clinical trials of efavirenz in antiretroviral-naive patients: a systematic review. AIDS Rev. 2010 Apr-Jun;12(2):67-75. Review. — View Citation

Haubrich RH, Riddler SA, DiRienzo AG, Komarow L, Powderly WG, Klingman K, Garren KW, Butcher DL, Rooney JF, Haas DW, Mellors JW, Havlir DV; AIDS Clinical Trials Group (ACTG) A5142 Study Team. Metabolic outcomes in a randomized trial of nucleoside, nonnucl — View Citation

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. — View Citation

Simpson KN, Dietz B, Baran RW, Garren KW, Riddler SA, Bhor M, Haubrich RH. Economic modeling of the combined effects of HIV-disease, cholesterol and lipoatrophy based on ACTG 5142 trial data. Cost Eff Resour Alloc. 2011 May 8;9:5. doi: 10.1186/1478-7547-9 — View Citation

Von Burg R, Stout T. Paraldehyde. J Appl Toxicol. 1991 Oct;11(5):379-81. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time from study entry to virologic failure
Primary	time from study entry to regimen completion
Secondary	20 % or more loss in peripheral fat
Secondary	increase in lactic acid levels at least 2-4old above the upper limit of normal (ULN)
Secondary	20 % or more increase in truncal fat accumulation
Secondary	fasting cholesterol level equal to or greater than 240 mg/dl
Secondary	Grade 3 or greater elevation in fasting triglyceride levels
Secondary	change from baseline in insulin resistance		at Weeks 24, 48 and 96
Secondary	change from baseline of whole-body bone density and whole-body bone mineral content		at Weeks 48 and 96
Secondary	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
Secondary	number of antiretroviral classes with resistance mutations at virologic failure
Secondary	number of missed medication doses		4 days prior
Secondary	change from baseline in self-reported symptoms OR occurrence of reporting an increase in symptoms		at Weeks 4, 48, 72 and 96
Secondary	change from baseline in body image OR occurrence of reporting body image distress		at Weeks 24, 48, 72 and 96
Secondary	time until treatment-limiting toxicity OR occurrence of Grades 3 or 4 toxicity

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