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

NCT00050895 | Completed Phase 3

• 5 other identifiers: A514210085ACTG A5142A5152sA5160s
• Study Type: interventional
• Target: 775
• Locations: 2 countries
• Sites: 60

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.

Conditions

HIV Infections

Keywords

Reverse Transcriptase Inhibitors; HIV Protease Inhibitors; Drug Therapy, Combination; Delayed Action Preparations; Treatment Naive; HIV-1

Outcome Measures

Primary Outcomes (2)

• Time from study entry to virologic failure

• time from study entry to regimen completion

Secondary Outcomes (13)

• 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

Interventions

Lopinavir/ritonavir DRUG

Efavirenz DRUG

Stavudine DRUG

Zidovudine DRUG

Lamivudine DRUG

Tenofovir disoproxil fumarate DRUG

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (60)

Alabama Therapeutics CRS

Birmingham, Alabama, 35924, United States

Location

USC CRS

Los Angeles, California, 90033-1079, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90095-1793, United States

Location

Stanford CRS

Palo Alto, California, 94305-5107, United States

Location

UC Davis Medical Center

Sacramento, California, 95814, United States

Location

Univ. of California Davis Med. Ctr., ACTU

Sacramento, California, United States

Location

Ucsd, Avrc Crs

San Diego, California, 92103, United States

Location

Ucsf Aids Crs

San Francisco, California, 94110, United States

Location

Santa Clara Valley Med. Ctr.

San Jose, California, 94305-5107, United States

Location

San Mateo County AIDS Program

San Mateo, California, 94305-5107, United States

Location

Harbor-UCLA Med. Ctr. CRS

Torrance, California, 90502-2052, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80262-3706, United States

Location

Georgetown University CRS (GU CRS)

Washington D.C., District of Columbia, 20007, United States

Location

Univ. of Miami AIDS CRS

Miami, Florida, 33136, United States

Location

The Ponce de Leon Ctr. CRS

Atlanta, Georgia, 30308, United States

Location

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, 96816, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611-3015, United States

Location

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, 60612-3806, United States

Location

Cook County Hosp. CORE Ctr.

Chicago, Illinois, 60612, United States

Location

Methodist Hosp. of Indiana

Indianapolis, Indiana, 46202-1261, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 46202-5250, United States

Location

Indiana Univ. School of Medicine, Wishard Memorial

Indianapolis, Indiana, 46202, United States

Location

Univ. of Iowa Healthcare, Div. of Infectious Diseases

Iowa City, Iowa, 52242-1201, United States

Location

IHV Baltimore Treatment CRS

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, 02114, United States

Location

Bmc Actg Crs

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, 02215, United States

Location

Brigham and Women's Hosp. ACTG CRS

Boston, Massachusetts, 02215, United States

Location

SSTAR, Family Healthcare Ctr.

Fall River, Massachusetts, United States

Location

University of Minnesota, ACTU

Minneapolis, Minnesota, 55455-0392, United States

Location

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, 63108-2138, United States

Location

Washington U CRS

St Louis, Missouri, 63108-2138, United States

Location

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

Omaha, Nebraska, 68198-5130, United States

Location

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, 14215, United States

Location

Beth Israel Med. Ctr., ACTU

New York, New York, 10003, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016-6481, United States

Location

Cornell CRS

New York, New York, 10021, United States

Location

Columbia Univ., HIV Prevention and Treatment Medical Ctr.

New York, New York, 10032-3784, United States

Location

HIV Prevention & Treatment CRS

New York, New York, United States

Location

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

New York, New York, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642-0001, United States

Location

AIDS Care CRS

Rochester, New York, United States

Location

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

Rochester, New York, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 27514, United States

Location

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, 27710, United States

Location

Wake County Health and Human Services CRS

Raleigh, North Carolina, United States

Location

Univ. of Cincinnati CRS

Cincinnati, Ohio, 45267-0405, United States

Location

Case CRS

Cleveland, Ohio, 44106-5083, United States

Location

MetroHealth CRS

Cleveland, Ohio, 44109-1998, United States

Location

Cleveland Clinic Foundation, Div. of Medicine, Infectious Diseases

Cleveland, Ohio, 44109-5083, United States

Location

The Ohio State Univ. AIDS CRS

Columbus, Ohio, 43210-1282, United States

Location

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

Philadelphia, Pennsylvania, 19104, United States

Location

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, 19401, United States

Location

Pitt CRS

Pittsburgh, Pennsylvania, 15213-2582, United States

Location

Rhode Island Hosp.

Providence, Rhode Island, 02906, United States

Location

The Miriam Hosp. ACTG CRS

Providence, Rhode Island, 02906, United States

Location

Vanderbilt Therapeutics CRS

Nashville, Tennessee, 37203, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104, United States

Location

Durban Adult HIV CRS

Durban, KwaZulu-Natal, South Africa

Location

Related Publications (13)

• 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.

  PMID: 10714566 BACKGROUND

• 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.

  PMID: 12689734 BACKGROUND

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

  PMID: 1783744 RESULT

• 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.

  PMID: 19417580 RESULT

• 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.

  PMID: 20571601 RESULT

• 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.

  PMID: 21548986 RESULT

• 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.

  PMID: 38160309 DERIVED

• 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.

  PMID: 33901188 DERIVED

• 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.

  PMID: 32829410 DERIVED

• 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.

  PMID: 24979445 DERIVED

• 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.

  PMID: 23276808 DERIVED

• 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.

  PMID: 20871389 DERIVED

• 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.

  PMID: 18480202 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Lopinavir; efavirenz; Stavudine; Zidovudine; Lamivudine; Tenofovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thymidine; Pyrimidine Nucleosides; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Zalcitabine; Deoxycytidine; Cytidine; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sharon Riddler, MD

  University of Pittsburgh

  STUDY CHAIR

• Richard Haubrich, MD

  University of California, San Diego, Division of Infectious Diseases

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2002
• First Posted: January 1, 2003
• Study Completion: March 1, 2006
• Last Updated: November 1, 2021

Record last verified: 2021-10

Locations

ZA (1); US (59)