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

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00050895

Purpose

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	Intervention	Phase
HIV Infections	Drug: Lopinavir/ritonavir Drug: Efavirenz Drug: Stavudine Drug: Zidovudine Drug: Lamivudine Drug: Tenofovir disoproxil fumarate	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: Diabetes Medicines HIV/AIDS HIV/AIDS Medicines

Drug Information available for: Zidovudine Lamivudine Tenofovir Efavirenz Ritonavir Lopinavir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Stavudine

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Time from study entry to virologic failure
time from study entry to regimen completion

Secondary Outcome Measures:

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

Estimated Enrollment:	775
Study Completion Date:	May 2007

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.

Eligibility

Ages Eligible for Study:	13 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

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

ClinicalTrials.gov Identifier:	NCT00050895 History of Changes
Other Study ID Numbers:	ACTG A5142, A5152s, A5160s, DAIDS-ES ID 10085
Study First Received:	December 30, 2002
Last Updated:	June 23, 2011
Health Authority:	United States: Food and Drug Administration