AzTrials
AzTrials

HIV InfectionsPhase 3NCT00013520

Comparison of Three Different Initial Treatments Without Protease Inhibitors for HIV Infection

A Phase 3 study testing Abacavir sulfate, Lamivudine and Zidovudine, Atazanavir and Lamivudine/Zidovudine 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

The purpose of this study is to compare the effectiveness, safety, and tolerability of 3 anti-HIV combination treatments that do not use protease inhibitors (PIs). The current rule for starting treatment of HIV infection is to combine members from different classes of anti-HIV drugs, such as 2 nucleoside reverse… Read more about this study

Who is it for?
Ages 16 years and older
Conditions the study is for
HIV Infections
What is being tested?
Abacavir sulfate, Lamivudine and Zidovudine, Atazanavir and Lamivudine/Zidovudine
How many people
1,125 participants
Where
60 sitesin 2 countries
Study dates
Start not givento Jun 2005
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 16 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Patients may be eligible for this study if they:
  • Are HIV-positive.
  • Have a viral load of at least 400 copies/ml within 90 days prior to study entry.
  • Are at least 16 years old.
  • Weigh at least 40 kg.
  • Have a negative pregnancy test within 48 hours before starting study drugs, if female and able to have children.
  • Agree to use 2 effective methods of birth control while taking, and for 3 months after stopping, the study medications.
  • Provide written consent of a parent or guardian, if under 18 years of age.

Who cannot join

  • Patients will not be eligible for this study if they:
  • Have taken anti-HIV drugs in the past.
  • Are allergic to any of the study drugs or ingredients.
  • Are pregnant or breast-feeding.
  • Have taken any of the following drugs within 14 days prior to study entry: amiodarone, astemizole, bepridil, cisapride, ergot or ergot derivatives, systemic itraconazole, systemic ketoconazole, midazolam, propoxyphene, quinidine, rifampin, terfenadine, thalidomide, triazolam, or St. John's wort.
  • Have taken drugs that influence the immune system, HIV or other vaccines, or investigational drugs within 30 days prior to study entry. Prednisone at a dose of 10 mg or less daily is allowed.
Show all 13Show fewer
  • Have taken drugs or been hospitalized for serious infections or medical illnesses within 14 days prior to study entry.
  • Have growths or tumors that require drug therapy.
  • Have Pneumocystis carinii pneumonia that is not clinically stable and whose treatment is not completed at least 7 days prior to study entry.
  • Have infections or medical illnesses that are not under control or that have not received complete treatment before study entry.
  • Have any condition that, in the opinion of the investigator, would prevent them from properly participating in the study.
  • Abuse drugs or alcohol.
  • This study has been updated to exclude patients who are receiving systemic itraconazole and rifabutin.

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

  • Johns Hopkins Adult AIDS CRS

    Baltimore, Maryland, 21287

  • Alabama Therapeutics CRS

    Birmingham, Alabama, 35294

  • 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

  • SUNY - Buffalo, Erie County Medical Ctr.

    Buffalo, New York, 14215

  • Unc Aids Crs

    Chapel Hill, North Carolina, 275997215

  • Northwestern University CRS

    Chicago, Illinois, 60611

  • Rush Univ. Med. Ctr. ACTG CRS

    Chicago, Illinois, 60612

  • Cook County Hosp. CORE Ctr.

    Chicago, Illinois

  • Univ. of Cincinnati CRS

    Cincinnati, Ohio, 452670405

  • Case CRS

    Cleveland, Ohio, 44106

  • MetroHealth CRS

    Cleveland, Ohio, 441091998

  • The Ohio State Univ. AIDS CRS

    Columbus, Ohio, 432101228

  • Duke Univ. Med. Ctr. Adult CRS

    Durham, North Carolina, 27710

  • SSTAR, Family Healthcare Ctr.

    Fall River, Massachusetts

  • Regional Center for Infectious Disease, Wendover Medical Center CRS

    Greensboro, North Carolina, 27401

  • Univ. of Hawaii at Manoa, Leahi Hosp.

    Honolulu, Hawaii, 96816

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

    Indianapolis, Indiana, 462025250

  • Indiana Univ. School of Medicine, Wishard Memorial

    Indianapolis, Indiana, 46202

  • Methodist Hosp. of Indiana

    Indianapolis, Indiana, 46202

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

    Iowa City, Iowa, 52242

  • USC CRS

    Los Angeles, California, 900331079

  • UCLA CARE Center CRS

    Los Angeles, California, 90095

  • Univ. of Miami AIDS CRS

    Miami, Florida, 331361013

  • University of Minnesota, ACTU

    Minneapolis, Minnesota, 55455

  • Vanderbilt Therapeutics CRS

    Nashville, Tennessee, 37203

  • Beth Israel Med. Ctr., ACTU

    New York, New York, 10003

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

    New York, New York, 10011

  • NY Univ. HIV/AIDS CRS

    New York, New York, 10016

  • Cornell CRS

    New York, New York, 10021

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

    New York, New York, 10032

  • HIV Prevention & Treatment CRS

    New York, New York

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

    Omaha, Nebraska, 681985130

  • Stanford CRS

    Palo Alto, California

  • Philadelphia Veterans Admin. Med. Ctr. A6205 CRS

    Philadelphia, Pennsylvania, 19104

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

    Philadelphia, Pennsylvania, 19104

  • Hosp. of the Univ. of Pennsylvania CRS

    Philadelphia, Pennsylvania

  • Pitt CRS

    Pittsburgh, Pennsylvania, 15213

  • The Miriam Hosp. ACTG CRS

    Providence, Rhode Island, 02906

  • Rhode Island Hosp.

    Providence, Rhode Island

  • Univ. of Rochester ACTG CRS

    Rochester, New York, 14642

  • 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

  • San Mateo County AIDS Program

    San Mateo, California, 943055107

  • Willow Clinic A0507 CRS

    San Mateo, California

  • University of Washington AIDS CRS

    Seattle, Washington, 98104

  • St. Louis ConnectCare, Infectious Diseases Clinic

    St Louis, Missouri

  • Washington U CRS

    St Louis, Missouri

  • Harbor-UCLA Med. Ctr. CRS

    Torrance, California, 90502

  • Georgetown University CRS (GU CRS)

    Washington D.C., District of Columbia, 20007

Other trials in United States

Puerto Rico1 site

  • Puerto Rico-AIDS CRS

    San Juan, 009365067

Other trials in Puerto Rico

About this study

Official title: Phase III, Randomized, Double-Blind Comparison of Three Protease Inhibitor-Sparing Regimens for the Initial Treatment of HIV Infection

The purpose of this study is to compare the effectiveness, safety, and tolerability of 3 anti-HIV combination treatments that do not use protease inhibitors (PIs).

The current rule for starting treatment of HIV infection is to combine members from different classes of anti-HIV drugs, such as 2 nucleoside reverse transcriptase inhibitors (NRTIs) and either a PI or a nonnucleoside reverse transcriptase inhibitor (NNRTI). However, these combinations can be complicated and difficult to take, can cause a number of side effects, and may become ineffective. Combinations that are simpler, better tolerated, and more effective are needed. Because PIs can cause long-term side effects and because HIV can become resistant to many of them at the same time, anti-HIV combination treatments that do not use PIs are being tested.

Read the detailed description

Current treatment guidelines recommend combination regimens of 2 nucleoside analogues with either a PI or an NNRTI for the initial treatment of HIV infection. However, the efficacy of current regimens is limited by their complexity, pharmacokinetic characteristics, short- and long-term side effects, and drug-resistance profiles at the time of virologic failure. Consequently, the identification of new initial regimens that are simpler, better tolerated, preserve treatment options in the event of failure, and improve antiretroviral potency is needed. In addition, recent concern over the long-term toxicities of PIs and the extensive cross-resistance among the available PIs have led to the testing of PI-sparing regimens.

Participants will be in this study for a minimum of 120 weeks and a maximum of approximately 4 years. In Step 1, patients are randomly selected to receive 1 of 3 blinded treatment regimens: abacavir (ABC)/lamivudine (3TC)/zidovudine (ZDV)/efavirenz (EFV), ABC/3TC/ZDV, or 3TC/ZDV/EFV. Patients with confirmed virologic failure on Step 1 and two successive plasma HIV RNA levels of 10,000 copies/ml or greater must register to Step 2. Patients with confirmed virologic failure on Step 1 and whose plasma HIV RNA is under 10,000 copies/ml may remain on Step 1 or register to Step 2. [AS PER AMENDMENT 04/11/03: Discontinuation of Arm B was recommended. Consequently, Arms A and C were unblinded to EFV but not to ABC. A number of options are available for patients originally randomized to Arm B.]

Step 2 is open label. Regimens include 2 or 3 nucleoside reverse transcriptase inhibitors (NRTIs) in combination with EFV, atazanavir (ATZ), ritonavir-boosted ATZ, or tenofovir disoproxil fumarate (TDF). Patients on Arm B treatment who have an HIV RNA level less than 200 copies/ml within the past 8 weeks are eligible for randomization to open-label intensification of Arm B on Step 3.

Step 3 regimens include ABC/3TC/ZDV plus either EFV or TDF. Patients with evidence of treatment-limiting toxicity to Step 3 study drugs have the option of substituting d4T for ZDV, ddI for ABC or TDF, and/or NVP for EFV. Patients with confirmed virologic failure on Step 3 and whose plasma HIV RNA is less than 10,000 copies/ml may either remain on Step 3 or register to Step 4. Patients with two successive plasma HIV RNA levels of 10,000 copies/ml or greater on Step 3 must register to Step 4.

Step 4 is open label. Regimens include two or three NRTIs plus EFV, ATV, ritonavir-boosted ATV, or TDF. Clinical assessments and laboratory evaluations are done at entry, at Weeks 2, 4, 6, 8, 12, 16, 20, 24, and then every 8 weeks thereafter for the duration of the study. Evaluations are also required when a protocol-allowed drug substitution is made.

In addition, 3 substudies are being conducted: a neurology substudy for efavirenz, a pharmacology substudy for atazanavir, and a viral dynamics substudy.

Conditions
HIV Infections
Being tested
Abacavir sulfate, Lamivudine and Zidovudine, Atazanavir, Lamivudine/Zidovudine, Abacavir sulfate, Efavirenz
Keywords
HIV-1, Didanosine, Drug Therapy, Combination, Zidovudine, Nevirapine, Stavudine, Lamivudine, RNA, Viral, Reverse Transcriptase Inhibitors, Anti-HIV Agents, Viral Load, Combivir, BMS 232632, Efavirenz, Treatment Naive
Medical subject headings
HIV Infections

What participants receive

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

  • Abacavir sulfate, Lamivudine and ZidovudineDrug

  • AtazanavirDrug

  • Lamivudine/ZidovudineDrug

  • Abacavir sulfateDrug

  • EfavirenzDrug

  • NevirapineDrug

  • LamivudineDrug

  • StavudineDrug

  • ZidovudineDrug

  • DidanosineDrug

Timeline

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

  1. First posted31 Aug 2001 (estimated)
  2. Study completionJun 2005

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
Enrolment
1,125 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00013520
Sponsor's protocol ID
A5095
Other IDs
10212, ACTG A5095, AACTG A5095, Substudy ACTG A5097s, Substudy AACTG 5107s, Substudy AACTG 5166s, Substudy ACTG A5166s, Substudy AACTG 5097s
Status last verified
May 2012
First submitted
16 Mar 2001
Last updated
21 May 2012
Results posted
No

Publications

  • H Ribaudo, D Clifford, R Gulick, C Shikuma, K Klingman, S Snyder, and E Acosta. Relationships between Efavirenz Pharmacokinetics, Side Effects, Drug Discontinuation, Virologic Response, and Race: Results from ACTG A5095/A5097s. CROI 2004. Abstract 132.

  • Feinberg J. Meeting notes from the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment. Trizivir vs. efavirenz: results from ACTG 5095. AIDS Clin Care. 2003 Sep;15(9):78-9.

    PubMed 14669723

  • Gulick RM, Ribaudo HJ, Shikuma CM, Lustgarten S, Squires KE, Meyer WA 3rd, Acosta EP, Schackman BR, Pilcher CD, Murphy RL, Maher WE, Witt MD, Reichman RC, Snyder S, Klingman KL, Kuritzkes DR; AIDS Clinical Trials Group Study A5095 Team. Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N Engl J Med. 2004 Apr 29;350(18):1850-61. doi: 10.1056/NEJMoa031772.

    PubMed 15115831

  • Clifford DB, Evans S, Yang Y, Acosta EP, Goodkin K, Tashima K, Simpson D, Dorfman D, Ribaudo H, Gulick RM. Impact of efavirenz on neuropsychological performance and symptoms in HIV-infected individuals. Ann Intern Med. 2005 Nov 15;143(10):714-21. doi: 10.7326/0003-4819-143-10-200511150-00008.

    PubMed 16287792

  • Gulick RM, Ribaudo HJ, Shikuma CM, Lalama C, Schackman BR, Meyer WA 3rd, Acosta EP, Schouten J, Squires KE, Pilcher CD, Murphy RL, Koletar SL, Carlson M, Reichman RC, Bastow B, Klingman KL, Kuritzkes DR; AIDS Clinical Trials Group (ACTG) A5095 Study Team. Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection: a randomized controlled trial. JAMA. 2006 Aug 16;296(7):769-81. doi: 10.1001/jama.296.7.769.

    PubMed 16905783

  • Ribaudo HJ, Kuritzkes DR, Schackman BR, Acosta EP, Shikuma CM, Gulick RM. Design issues in initial HIV-treatment trials: focus on ACTG A5095. Antivir Ther. 2006;11(6):751-60.

    PubMed 17310819

  • Kuritzkes DR, Ribaudo HJ, Squires KE, Koletar SL, Santana J, Riddler SA, Reichman R, Shikuma C, Meyer WA 3rd, Klingman KL, Gulick RM; ACTG A5166s Protocol Team. Plasma HIV-1 RNA dynamics in antiretroviral-naive subjects receiving either triple-nucleoside or efavirenz-containing regimens: ACTG A5166s. J Infect Dis. 2007 Apr 15;195(8):1169-76. doi: 10.1086/512619. Epub 2007 Mar 6.

    PubMed 17357053

  • Schackman BR, Ribaudo HJ, Krambrink A, Hughes V, Kuritzkes DR, Gulick RM. Racial differences in virologic failure associated with adherence and quality of life on efavirenz-containing regimens for initial HIV therapy: results of ACTG A5095. J Acquir Immune Defic Syndr. 2007 Dec 15;46(5):547-54. doi: 10.1097/qai.0b013e31815ac499.

    PubMed 18193496

  • Paredes R, Lalama CM, Ribaudo HJ, Schackman BR, Shikuma C, Giguel F, Meyer WA 3rd, Johnson VA, Fiscus SA, D'Aquila RT, Gulick RM, Kuritzkes DR; AIDS Clinical Trials Group (ACTG) A5095 Study Team. Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. J Infect Dis. 2010 Mar;201(5):662-71. doi: 10.1086/650543.

    PubMed 20102271

  • 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

  • Lok JJ, Hunt PW, Collier AC, Benson CA, Witt MD, Luque AE, Deeks SG, Bosch RJ. The impact of age on the prognostic capacity of CD8+ T-cell activation during suppressive antiretroviral therapy. AIDS. 2013 Aug 24;27(13):2101-10. doi: 10.1097/QAD.0b013e32836191b1.

    PubMed 24326304

  • Schouten JT, Krambrink A, Ribaudo HJ, Kmack A, Webb N, Shikuma C, Kuritzkes DR, Gulick RM. Substitution of nevirapine because of efavirenz toxicity in AIDS clinical trials group A5095. Clin Infect Dis. 2010 Mar 1;50(5):787-91. doi: 10.1086/650539.

    PubMed 20121419

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Abacavir sulfate, Lamivudine and Zidovudine, Atazanavir and Lamivudine/Zidovudine 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 8 inclusion and 13 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 21 May 2012. 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, Puerto Rico. 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.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00013520, which also lists 15 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 21 May 2012.

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