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HIV InfectionsPhase 3NCT00050895

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

A Phase 3 study testing Lopinavir/ritonavir, Efavirenz and Stavudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 60 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 13 years and older
Conditions the study is for
HIV Infections
What is being tested?
Lopinavir/ritonavir, Efavirenz and Stavudine
How many people
775 participants
Where
60 sitesin 2 countries
Study dates
Start not givento Mar 2006
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

60 sites in 2 countries.

60 sites in 2 countries

United States59 sites

  • The Ponce de Leon Ctr. CRS

    Atlanta, Georgia, 30308

  • University of Colorado Hospital CRS

    Aurora, Colorado, 80262-3706

  • IHV Baltimore Treatment CRS

    Baltimore, Maryland, 21201

  • Johns Hopkins Adult AIDS CRS

    Baltimore, Maryland, 21287

  • Alabama Therapeutics CRS

    Birmingham, Alabama, 35924

  • Massachusetts General Hospital ACTG CRS

    Boston, Massachusetts, 02114

  • Bmc Actg Crs

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Med. Ctr., ACTG CRS

    Boston, Massachusetts, 02215

  • Brigham and Women's Hosp. ACTG CRS

    Boston, Massachusetts, 02215

  • SUNY - Buffalo, Erie County Medical Ctr.

    Buffalo, New York, 14215

  • Unc Aids Crs

    Chapel Hill, North Carolina, 27514

  • Northwestern University CRS

    Chicago, Illinois, 60611-3015

  • Rush Univ. Med. Ctr. ACTG CRS

    Chicago, Illinois, 60612-3806

  • Cook County Hosp. CORE Ctr.

    Chicago, Illinois, 60612

  • Univ. of Cincinnati CRS

    Cincinnati, Ohio, 45267-0405

  • Case CRS

    Cleveland, Ohio, 44106-5083

  • MetroHealth CRS

    Cleveland, Ohio, 44109-1998

  • Cleveland Clinic Foundation, Div. of Medicine, Infectious Diseases

    Cleveland, Ohio, 44109-5083

  • The Ohio State Univ. AIDS CRS

    Columbus, Ohio, 43210-1282

  • Duke Univ. Med. Ctr. Adult CRS

    Durham, North Carolina, 27710

  • SSTAR, Family Healthcare Ctr.

    Fall River, Massachusetts

  • Univ. of Hawaii at Manoa, Leahi Hosp.

    Honolulu, Hawaii, 96816

  • Methodist Hosp. of Indiana

    Indianapolis, Indiana, 46202-1261

  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic

    Indianapolis, Indiana, 46202-5250

  • Indiana Univ. School of Medicine, Wishard Memorial

    Indianapolis, Indiana, 46202

  • Univ. of Iowa Healthcare, Div. of Infectious Diseases

    Iowa City, Iowa, 52242-1201

  • USC CRS

    Los Angeles, California, 90033-1079

  • UCLA CARE Center CRS

    Los Angeles, California, 90095-1793

  • Univ. of Miami AIDS CRS

    Miami, Florida, 33136

  • University of Minnesota, ACTU

    Minneapolis, Minnesota, 55455-0392

  • Vanderbilt Therapeutics CRS

    Nashville, Tennessee, 37203

  • Beth Israel Med. Ctr., ACTU

    New York, New York, 10003

  • NY Univ. HIV/AIDS CRS

    New York, New York, 10016-6481

  • Cornell CRS

    New York, New York, 10021

  • Columbia Univ., HIV Prevention and Treatment Medical Ctr.

    New York, New York, 10032-3784

  • HIV Prevention & Treatment CRS

    New York, New York

  • Weill Med. College of Cornell Univ., The Cornell CTU

    New York, New York

  • Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.

    Omaha, Nebraska, 68198-5130

  • Stanford CRS

    Palo Alto, California, 94305-5107

  • Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.

    Philadelphia, Pennsylvania, 19104

  • Hosp. of the Univ. of Pennsylvania CRS

    Philadelphia, Pennsylvania, 19401

  • Pitt CRS

    Pittsburgh, Pennsylvania, 15213-2582

  • Rhode Island Hosp.

    Providence, Rhode Island, 02906

  • The Miriam Hosp. ACTG CRS

    Providence, Rhode Island, 02906

  • Wake County Health and Human Services CRS

    Raleigh, North Carolina

  • Univ. of Rochester ACTG CRS

    Rochester, New York, 14642-0001

  • AIDS Care CRS

    Rochester, New York

  • McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit

    Rochester, New York

  • UC Davis Medical Center

    Sacramento, California, 95814

  • Univ. of California Davis Med. Ctr., ACTU

    Sacramento, California

  • Ucsd, Avrc Crs

    San Diego, California, 92103

  • Ucsf Aids Crs

    San Francisco, California, 94110

  • Santa Clara Valley Med. Ctr.

    San Jose, California, 94305-5107

  • San Mateo County AIDS Program

    San Mateo, California, 94305-5107

  • University of Washington AIDS CRS

    Seattle, Washington, 98104

  • St. Louis ConnectCare, Infectious Diseases Clinic

    St Louis, Missouri, 63108-2138

  • Washington U CRS

    St Louis, Missouri, 63108-2138

  • Harbor-UCLA Med. Ctr. CRS

    Torrance, California, 90502-2052

  • Georgetown University CRS (GU CRS)

    Washington D.C., District of Columbia, 20007

Other trials in United States

South Africa1 site

  • Durban Adult HIV CRS

    Durban, KwaZulu-Natal

Other trials in South Africa

About this study

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

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.

Read the 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.

Conditions
HIV Infections
Being tested
Lopinavir/ritonavir, Efavirenz, Stavudine, Zidovudine, Lamivudine
Keywords
Reverse Transcriptase Inhibitors, HIV Protease Inhibitors, Drug Therapy, Combination, Delayed Action Preparations, Treatment Naive, HIV-1
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lopinavir/ritonavirDrug

  • EfavirenzDrug

  • StavudineDrug

  • ZidovudineDrug

  • LamivudineDrug

  • Tenofovir disoproxil fumarateDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time from study entry to virologic failure

  2. time from study entry to regimen completion

Secondary outcomes (13)

  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

    Measured: at Weeks 24, 48 and 96

  7. change from baseline of whole-body bone density and whole-body bone mineral content

    Measured: 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

    Measured: 4 days prior

  11. change from baseline in self-reported symptoms OR occurrence of reporting an increase in symptoms

    Measured: at Weeks 4, 48, 72 and 96

  12. change from baseline in body image OR occurrence of reporting body image distress

    Measured: at Weeks 24, 48, 72 and 96

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jan 2003 (estimated)
  2. Study completionMar 2006

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
775 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00050895
Sponsor's protocol ID
A5142
Other IDs
10085, ACTG A5142, A5152s, A5160s
Status last verified
Oct 2021
First submitted
30 Dec 2002
Last updated
1 Nov 2021
Results posted
No

Publications

  • 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. doi: 10.1097/00002030-200001070-00005.

    PubMed 10714566

  • 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. doi: 10.1016/s0197-2456(02)00321-5.

    PubMed 12689734

  • Von Burg R, Stout T. Paraldehyde. J Appl Toxicol. 1991 Oct;11(5):379-81. doi: 10.1002/jat.2550110515. No abstract available.

    PubMed 1783744

  • 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, nonnucleoside and protease inhibitor-sparing regimens for initial HIV treatment. AIDS. 2009 Jun 1;23(9):1109-18. doi: 10.1097/QAD.0b013e32832b4377.

    PubMed 19417580

  • 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.

    PubMed 20571601

  • 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: 10.1186/1478-7547-9-5.

    PubMed 21548986

  • Cardone KM, Dudek S, Keat K, Bradford Y, Cindi Z, Daar ES, Gulick R, Riddler SA, Lennox JL, Sinxadi P, Haas DW, Ritchie MD. Lymphocyte Count Derived Polygenic Score and Interindividual Variability in CD4 T-cell Recovery in Response to Antiretroviral Therapy. Pac Symp Biocomput. 2024;29:594-610.

    PubMed 38160309

  • Li B, Veturi Y, Verma A, Bradford Y, Daar ES, Gulick RM, Riddler SA, Robbins GK, Lennox JL, Haas DW, Ritchie MD. Tissue specificity-aware TWAS (TSA-TWAS) framework identifies novel associations with metabolic, immunologic, and virologic traits in HIV-positive adults. PLoS Genet. 2021 Apr 26;17(4):e1009464. doi: 10.1371/journal.pgen.1009464. eCollection 2021 Apr.

    PubMed 33901188

  • Leonard MA, Cindi Z, Bradford Y, Bourgi K, Koethe J, Turner M, Norwood J, Woodward B, Erdem H, Basham R, Baker P, Rebeiro PF, Sterling TR, Hulgan T, Daar ES, Gulick R, Riddler SA, Sinxadi P, Ritchie MD, Haas DW. Efavirenz Pharmacogenetics and Weight Gain Following Switch to Integrase Inhibitor-Containing Regimens. Clin Infect Dis. 2021 Oct 5;73(7):e2153-e2163. doi: 10.1093/cid/ciaa1219.

    PubMed 32829410

  • Mollan KR, Smurzynski M, Eron JJ, Daar ES, Campbell TB, Sax PE, Gulick RM, Na L, O'Keefe L, Robertson KR, Tierney C. Association between efavirenz as initial therapy for HIV-1 infection and increased risk for suicidal ideation or attempted or completed suicide: an analysis of trial data. Ann Intern Med. 2014 Jul 1;161(1):1-10. doi: 10.7326/M14-0293.

    PubMed 24979445

  • Bronke C, Almeida CM, McKinnon E, Roberts SG, Keane NM, Chopra A, Carlson JM, Heckerman D, Mallal S, John M. HIV escape mutations occur preferentially at HLA-binding sites of CD8 T-cell epitopes. AIDS. 2013 Mar 27;27(6):899-905. doi: 10.1097/QAD.0b013e32835e1616.

    PubMed 23276808

  • Hulgan T, Haubrich R, Riddler SA, Tebas P, Ritchie MD, McComsey GA, Haas DW, Canter JA. European mitochondrial DNA haplogroups and metabolic changes during antiretroviral therapy in AIDS Clinical Trials Group Study A5142. AIDS. 2011 Jan 2;25(1):37-47. doi: 10.1097/QAD.0b013e32833f9d02.

    PubMed 20871389

  • Riddler SA, Haubrich R, DiRienzo AG, Peeples L, Powderly WG, Klingman KL, Garren KW, George T, Rooney JF, Brizz B, Lalloo UG, Murphy RL, Swindells S, Havlir D, Mellors JW; AIDS Clinical Trials Group Study A5142 Team. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med. 2008 May 15;358(20):2095-106. doi: 10.1056/NEJMoa074609.

    PubMed 18480202

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lopinavir/ritonavir, Efavirenz and Stavudine in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 60 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 60 sites in United States, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time from study entry to virologic failure. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00050895, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.

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