Expired Study
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Sacramento, California 95814


Purpose:

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.


Study summary:

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.


Criteria:

Inclusion Criteria 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. Exclusion Criteria 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. - 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.


Study is Available At:


Original ID:

A5095


NCT ID:

NCT00013520


Secondary ID:

10212


Study Acronym:


Brief Title:

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


Official Title:

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


Overall Status:

Completed


Study Phase:

Phase 3


Genders:

Both


Minimum Age:

16 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institute of Allergy and Infectious Diseases (NIAID)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Endpoint Classification: Safety/Efficacy Study, P


Number of Arms:

0


Number of Groups:

0


Total Enrollment:

1125


Enrollment Type:


Overall Contact Information

Official Name:Roy Gulick, MD
Study Chair

Study Dates

Completion Date:June 2005
Completion Type:Actual
Verification Date:May 2012
Last Changed Date:May 17, 2012
First Received Date:March 16, 2001

Study Outcomes

There are no available Study Outcomes

Study Interventions

Intervention Type:Drug
Name:Abacavir sulfate, Lamivudine and Zidovudine
Intervention Type:Drug
Name:Atazanavir
Intervention Type:Drug
Name:Lamivudine/Zidovudine
Intervention Type:Drug
Name:Abacavir sulfate
Intervention Type:Drug
Name:Efavirenz
Intervention Type:Drug
Name:Nevirapine
Intervention Type:Drug
Name:Lamivudine
Intervention Type:Drug
Name:Stavudine
Intervention Type:Drug
Name:Zidovudine
Intervention Type:Drug
Name:Didanosine

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Institute of Allergy and Infectious Diseases (NIAID)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
Citation: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.
Reference Type:Results Reference
Citation: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.
PMID:14669723
Reference Type:Results Reference
Citation: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.
PMID:15115831
Reference Type:Results Reference
Citation: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. Summary for patients in: Ann Intern Med. 2005 Nov 15;143(10):I43.
PMID:16287792
Reference Type:Results Reference
Citation: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 1;201(5):662-71.
PMID:20102271
Reference Type:Results Reference
Citation: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.
PMID:18193496
Reference Type:Results Reference
Citation: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. Epub 2007 Mar 6.
PMID:17357053
Reference Type:Results Reference
Citation: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.
PMID:17310819
Reference Type:Results Reference
Citation: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.
PMID:16905783

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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