Optimizing Treatment for Treatment-Experienced, HIV-Infected People

NCT00537394 | Completed Phase 3 Results

• 4 other identifiers: A524110395ACTG A5241OPTIONS
• Study Type: interventional
• Target: 517
• Locations: 2 countries
• Sites: 64

Brief Summary

The goal of anti-HIV therapy is to prevent HIV from replicating. Long-term control of HIV requires at least two anti-HIV drugs that are active against the virus. Drug resistance is a problem for many treatment-experienced, HIV-infected people. The purpose of this study was to determine the benefit of adding a nucleoside reverse transcriptase inhibitor (NRTI) to a new anti-HIV drug regimen for the suppression of HIV.

Conditions

HIV Infections

Keywords

Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With Regimen Failure, Defined as a Confirmed Virologic Failure or Discontinuation of Randomized NRTI Component of Study Treatment

  Virologic failure defined as confirmed plasma HIV-1 RNA meeting 1 of the following 4 criteria: \< 1.0 log10 copies/mL reduction from baseline level and \>= 200 copies/mL at or after week 12 evaluation; \>= 200 copies/mL after 1 measurement \< 200 copies/mL; absence of any values \< 200 copies/mL by and including week 24 evaluation; \>= 200 copies/mL at week 48 evaluation. Discontinuation of Randomized NRTI component of Study Treatment is defined as permanently stopping all NRTIs among those randomized to add NRTIs, or starting any NRTI among those randomized to omit NRTIs. Subjects leaving the study for reasons other than death, relocation, incarceration, or site closure were reviewed for the discontinuation outcome by a blinded, independent panel. Additionally, any participant failing to start study treatment after randomization and prior to closure was also reviewed. Results report percent of participants reaching regimen failure outcome by week 48 evaluation using Kaplan-Meier method.

  From study entry to end of Week 48 evaluation window

Secondary Outcomes (14)

• Time From Treatment Dispensation to First Grade 3 or Higher (and at Least One Grade Higher Than Baseline) Signs/Symptom or Laboratory Abnormality

  From treatment dispensation to week 96 study visit

• Time From Treatment Dispensation to First Study ARV Modification (Excluding NRTIs, if Applicable)

  From treatment dispensation to week 96 study visit

• Time From Randomization to Discontinuation of Randomized NRTI Component of Study Treatment

  From randomization to week 96 study visit

• Time From Randomization to Confirmed Virological Failure

  From randomization to week 96 study visit

• Number of Participants With Plasma HIV-1 Viral Load < 50 Copies/ml

  At Weeks 24, 48, 96

Study Arms (3)

A

EXPERIMENTAL

Regimen with higher predicted activity assigned by the study plus at least 2 NRTIs (personalized choice from expert recommendation) for 96 weeks. A 3-4 drug regimen was selected from the drugs listed to the right.

Drug: Enfuvirtide; Drug: Raltegravir; Drug: Darunavir; Drug: Tipranavir; Drug: Etravirine; Drug: Maraviroc

B

EXPERIMENTAL

Regimen with higher predicted activity assigned by the study without NRTIs for 96 weeks. A 3-4 drug regimen was selected from the drugs listed to the right.

Drug: Enfuvirtide; Drug: Raltegravir; Drug: Darunavir; Drug: Tipranavir; Drug: Etravirine; Drug: Maraviroc

C

OTHER

Regimen with lower predicted activity assigned plus at least 2 NRTIs (personalized choice from expert recommendation) for 96 weeks. A 3-4 drug regimen was selected from the drugs listed to the right.

Drug: Enfuvirtide; Drug: Raltegravir; Drug: Darunavir; Drug: Tipranavir; Drug: Etravirine; Drug: Maraviroc

Interventions

Enfuvirtide DRUG

90mg subcutaneously twice daily

A; B; C

Raltegravir DRUG

400 mg twice daily

A; B; C

Darunavir DRUG

Two 300-mg tablets twice daily, given with ritonavir 100mg twice daily (ritonavir not provided by the study)

A; B; C

Tipranavir DRUG

Two 250-mg capsules twice daily, given with ritonavir 100mg twice daily (ritonavir not provided by the study)

A; B; C

Etravirine DRUG

Two 100-mg tablets twice daily

A; B; C

Maraviroc DRUG

Dosage dependent on regimen in which maraviroc is included

A; B; C

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection
• Triple-class drug experience or resistance. More information on this criterion can be found in the protocol.
• Currently on a failing PI-containing regimen that includes 2 other ARVs with no regimen change for 8 weeks prior to study screening
• HIV viral load of 1000 copies/ml or more
• Hepatitis B surface antigen negative within 90 days of study entry
• Able to obtain NRTIs and ritonavir and have required ARVs at time of starting study intervention
• Willing to use acceptable forms of contraception
• Parent or legal guardian willing to provide consent, if applicable
• CD4 count result from a specimen drawn within 120 days prior to study entry
• If any previous HIV-1 viral co-receptor tropism result is available, then most recent specimen date and the tropism result of that specimen AND specimen date and tropism result of any test with either X4 or D/M result, if different from the first specimen, must be available
• Receipt of successful phenotype/genotype resistance results within 105 days prior to study treatment intervention assignment
• Study team identification of a study regimen and at least 2 NRTIs for participant to take
• Certain abnormal laboratory values. More information on this criterion can be found in the protocol.

You may not qualify if:

• Chronic, active hepatitis B virus infection (hepatitis B surface antigen positive or HBV DNA positive)
• Taking certain medications. More information on this criterion can be found in the protocol.
• Known allergy/sensitivity to components of two or more of the study-provided drugs or their formulations. For maraviroc, this includes hypersensitivity or history of allergy to soy lecithin or peanuts.
• Active drug or alcohol use that, in the opinion of the investigator, may interfere with the study
• Pregnancy or breastfeeding
• Use of any immunomodulator (interferons, interleukins, systemic corticosteroids, or cyclosporine), vaccine, or investigational therapy within 30 days prior to study treatment allocation/assignment
• Require certain medications prohibited with study treatment
• Serious illness requiring systemic treatment or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 14 days prior to study treatment allocation are not excluded.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: collaborator

Study Sites (64)

Alabama Therapeutics CRS

Birmingham, Alabama, 35294-2050, United States

Location

Miller Children's Hosp. Long Beach CA NICHD CRS

Long Beach, California, 90806, United States

Location

University of Southern California CRS

Los Angeles, California, 90033, United States

Location

Usc La Nichd Crs

Los Angeles, California, 90033, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS

Los Angeles, California, 90095-1752, United States

Location

Stanford AIDS Clinical Trials Unit CRS

Palo Alto, California, 94304-5350, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

Univ. of California San Francisco NICHD CRS

San Francisco, California, 94143, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Denver Public Health CRS

Denver, Colorado, 80204, United States

Location

Georgetown University CRS (GU CRS)

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

Location

Children's National Med. Ctr. ATN CRS

Washington D.C., District of Columbia, 20010, United States

Location

Howard Univ. Washington DC NICHD CRS

Washington D.C., District of Columbia, 20060, United States

Location

Pediatric Perinatal HIV Clinical Trials Unit CRS

Miami, Florida, 33136, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Rush University CRS

Chicago, Illinois, 60612, United States

Location

Tulane Univ. New Orleans NICHD CRS

New Orleans, Louisiana, 70112-2699, United States

Location

IHV Baltimore Treatment CRS

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS

Boston, Massachusetts, 02115, United States

Location

Bmc Actg Crs

Boston, Massachusetts, 02118, United States

Location

Boston Medical Center Ped. HIV Program NICHD CRS

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, 02215, United States

Location

Wayne State Univ. CRS

Detroit, Michigan, 48201, United States

Location

Henry Ford Hosp. CRS

Detroit, Michigan, 48202, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110, United States

Location

Cooper Univ. Hosp. CRS

Camden, New Jersey, 08103, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Rutgers - New Jersey Medical School CRS

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10011, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Nyu Ny Nichd Crs

New York, New York, 10016, United States

Location

Metropolitan Hosp. NICHD CRS

New York, New York, 10029, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

Columbia IMPAACT CRS

New York, New York, 10032, United States

Location

Harlem ACTG CRS

New York, New York, 10037, United States

Location

Trillium Health ACTG CRS

Rochester, New York, 14607, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Bronx-Lebanon Hosp. Ctr. CRS

The Bronx, New York, 10457, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27514, United States

Location

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, 27710, United States

Location

Cincinnati CRS

Cincinnati, Ohio, 45267-0405, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

MetroHealth CRS

Cleveland, Ohio, 44109, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

The Research & Education Group-Portland CRS

Portland, Oregon, 97210, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson Univ. Med. Ctr. CRS

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213-2582, United States

Location

The Miriam Hospital Clinical Research Site (TMH CRS) CRS

Providence, Rhode Island, 02906, United States

Location

St. Jude Children's Research Hospital CRS

Memphis, Tennessee, 38105, United States

Location

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

Trinity Health and Wellness Center CRS

Dallas, Texas, 75208, United States

Location

Houston AIDS Research Team CRS

Houston, Texas, 77030, United States

Location

Texas Children's Hospital CRS

Houston, Texas, 77030, United States

Location

Virginia Commonwealth Univ. Medical Ctr. CRS

Richmond, Virginia, 23298, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104, United States

Location

Puerto Rico AIDS Clinical Trials Unit CRS

San Juan, 00935, Puerto Rico

Location

University of Puerto Rico Pediatric HIV/AIDS Research Program CRS

San Juan, 00935, Puerto Rico

Location

San Juan City Hosp. PR NICHD CRS

San Juan, 00936, Puerto Rico

Location

Related Publications (6)

• Altmann A, Beerenwinkel N, Sing T, Savenkov I, Doumer M, Kaiser R, Rhee SY, Fessel WJ, Shafer RW, Lengauer T. Improved prediction of response to antiretroviral combination therapy using the genetic barrier to drug resistance. Antivir Ther. 2007;12(2):169-78. doi: 10.1177/135965350701200202.

  PMID: 17503659 BACKGROUND

• Eshleman SH, Husnik M, Hudelson S, Donnell D, Huang Y, Huang W, Hart S, Jackson B, Coates T, Chesney M, Koblin B. Antiretroviral drug resistance, HIV-1 tropism, and HIV-1 subtype among men who have sex with men with recent HIV-1 infection. AIDS. 2007 May 31;21(9):1165-74. doi: 10.1097/QAD.0b013e32810fd72e.

  PMID: 17502727 BACKGROUND

• Geretti AM. Clinical implications of HIV drug resistance to nucleoside and nucleotide reverse transcriptase inhibitors. AIDS Rev. 2006 Oct-Dec;8(4):210-20.

  PMID: 17219736 BACKGROUND

• Mallolas J, Blanco J, Labarga P, Vergara A, Ocampo A, Sarasa M, Arnedo M, Lopez-Pua Y, Garcia J, Juega J, Guelar A, Terron A, Dalmau D, Garcia I, Zarraga M, Martinez E, Carne X, Pumarola T, Escayola R, Gatell J. Inhibitory quotient as a prognostic factor of response to a salvage antiretroviral therapy containing ritonavir-boosted saquinavir. The CIVSA Study. HIV Med. 2007 May;8(4):226-33. doi: 10.1111/j.1468-1293.2007.00464.x.

  PMID: 17461850 BACKGROUND

• Gandhi RT, Tashima KT, Smeaton LM, Vu V, Ritz J, Andrade A, Eron JJ, Hogg E, Fichtenbaum CJ. Long-term Outcomes in a Large Randomized Trial of HIV-1 Salvage Therapy: 96-Week Results of AIDS Clinical Trials Group A5241 (OPTIONS). J Infect Dis. 2020 Apr 7;221(9):1407-1415. doi: 10.1093/infdis/jiz281.

  PMID: 31135883 DERIVED

• Tashima KT, Smeaton LM, Fichtenbaum CJ, Andrade A, Eron JJ, Gandhi RT, Johnson VA, Klingman KL, Ritz J, Hodder S, Santana JL, Wilkin T, Haubrich RH; A5241 Study Team. HIV Salvage Therapy Does Not Require Nucleoside Reverse Transcriptase Inhibitors: A Randomized, Controlled Trial. Ann Intern Med. 2015 Dec 15;163(12):908-17. doi: 10.7326/M15-0949. Epub 2015 Nov 24.

  PMID: 26595748 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Enfuvirtide; Raltegravir Potassium; Darunavir; tipranavir; etravirine; Maraviroc

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)

Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; HIV Envelope Protein gp41; Viral Fusion Proteins; Membrane Fusion Proteins; Membrane Proteins; Proteins; HIV Antigens; Antigens, Viral; Viral Proteins; env Gene Products, Human Immunodeficiency Virus; Gene Products, env; Retroviridae Proteins; Human Immunodeficiency Virus Proteins; Viral Envelope Proteins; Viral Structural Proteins; Antigens; Biological Factors; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social & Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301)628-3313

Study Officials

• Karen T. Tashima, MD

  Brown University

  STUDY CHAIR

• Richard H. Haubrich, MD

  Division of Infectious Diseases, UCSD Antiviral Research Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 27, 2007
• First Posted: October 1, 2007
• Study Start: January 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: April 1, 2013
• Last Updated: November 4, 2021
• Results First Posted: August 7, 2014

Record last verified: 2016-05

Locations

US (61); PR (3)