Safety and Effectiveness of Raltegravir and Darunavir/Ritonavir in Treatment-Naive HIV-Infected Adults - Full Text View

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Adult AIDS Clinical Trials Group
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00830804

Purpose

The purpose of this study is to assess the effectiveness and safety an antiretroviral therapy (ART) regimen consisting of raltegravir (RAL) and darunavir (DRV)/ritonavir (RTV) as first-line therapy in treatment-naïve participants.

Condition	Intervention	Phase
HIV Infections	Drug: Raltegravir Drug: Darunavir/Ritonavir	Phase 0

MedlinePlus related topics: AIDS

Drug Information available for: Ritonavir Darunavir Raltegravir Darunavir ethanolate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Pilot Efficacy and Safety Trial of Raltegravir Plus Darunavir/Ritonavir for Treatment-Naive HIV-1-Infected Subjects

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Proportion of ART-naive participants experiencing virologic failure after initiating RAL plus DRV/RTV [ Time Frame: Through Week 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Safety and tolerability of RAL plus DRV/RTV [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Virologic response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Early virologic response to the combination of RAL plus DRV/RTV [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Pretreatment drug resistance [ Time Frame: At screening ] [ Designated as safety issue: No ]
Impact of transmitted drug resistance on virologic outcomes to RAL plus DRV/RTV [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Adherence by self report [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Associations between virologic and/or other efficacy responses and plasma trough concentrations of RAL and DRV [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Pretreatment drug resistant minority viral variants in participants with virologic failure and in a random sample of participants who do not experience virologic failure [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Changes in fasting lipids [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Changes in CD4 counts, CD4 naive, and memory subsets, CD4 and CD8 activation state, CD4 and CD8 turnover, and levels of bacterial 16s DNAs [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Association between virologic response, immune activation, and turnover in defined T-cell maturation subsets, bacterial 16s DNA level, and CD4 restoration [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	111
Study Start Date:	April 2009
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Participants will receive RAL plus DRV/RTV orally daily for the duration of the trial.	Drug: Raltegravir 400 mg tablet taken orally daily Drug: Darunavir/Ritonavir 800 mg darunavir/ 100 mg ritonavir tablet taken orally daily

Detailed Description:

Despite the remarkable strides made in the treatment of HIV-1-infected persons over the last decade, current first-line ART regimens are imperfect. The ideal combination, unlike some current first-line options, would have uncompromised efficacy in the presence of transmitted drug-resistant variants. The primary purpose of this study is to estimate the cumulative proportion of ART-naive participants experiencing virologic failure after initiating a regimen consisting of raltegravir (RAL) and darunavir/ritonavir (DRV/RTV).

The study will last 52 weeks. All participants will follow the same treatment schedule and take RAL plus DRV/RTV orally daily for the duration of the trial.

After screening, all participants will have scheduled visits at Weeks 1, 4, 12, 36, 48, and 52. Medical/medication history, blood and urine collection, and liver function tests will occur at screening. A targeted physical exam and concomitant medications history will occur at all study visits. Blood and urine collection and liver function tests will occur at most study visits. For females, a pregnancy test will occur at screening and study entry.

RAL and DTV will be provided by the study. RTV will not be provided by the study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-infected
Plasma HIV RNA of at least 5,000 copies/mL within 90 days prior to study entry
HIV genotype performed at any time prior to study entry. More information on this criterion can be found in the protocol.
ARV drug-naive. More information on this criterion can be found in the protocol.
Negative hepatitis B surface antigen test performed within 90 days prior to study entry
Agree to use one form of medically-accepted contraceptive throughout the study and for 60 days after stopping study treatment. More information on this criterion can be found in the protocol.

Exclusion Criteria:

Serious illness requiring systemic treatment and/or hospitalization that, in the opinion of the investigator, would interfere with the study
Screening HIV genotype obtained any time prior to study entry with more than one DRV RAM (V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, I84V, and L89V) or L76 alone
Known major integrase inhibitor RAM(s), including N155H, Q148H/R/K, Y143C/R, and G140S
Severe renal insufficiency requiring hemodialysis or peritoneal dialysis
Treatment with immunomodulators within 30 days prior to study entry. More information on this criterion can be found in the protocol.
Current medications that are prohibited with any study medications. More information on this criterion can be found in the protocol.
Known allergy/sensitivity to study drugs or their formulations.
Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with the study
Certain abnormal laboratory results. More information on this criterion can be found in the protocol.
Pregnant or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00830804

Locations

United States, Alabama
AlabamaTherapeutics CRS	Not yet recruiting
Birmingham, Alabama, United States, 35294
Contact: Karen G. Savage 205-975-7925 kgsavage@uab.edu
Principal Investigator: Victoria A. Johnson, MD
United States, District of Columbia
Georgetown University CRS	Not yet recruiting
Washington, District of Columbia, United States, 20007
Contact: Abimael Lopez 202-687-7387 al374@georgetown.edu
Principal Investigator: Princy N. Kumar, MD
United States, Illinois
Northwestern University CRS	Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Baiba Berzins, MPH 312-695-4994 Baiba@northwestern.edu
Principal Investigator: Babafemi O. Taiwo, MD
United States, Missouri
Washington U CRS	Not yet recruiting
St.Louis, Missouri, United States, 63110
Contact: Michael Klebert, RN,C, PhD, ANP 1-314-747-1098 mklebert@im.wustl.edu
Principal Investigator: Edgar T. Overton, MD
United States, New York
Univ. of Rochester ACTG CRS	Not yet recruiting
Rochester, New York, United States, 14642
Contact: Carol Greisberger, RN, CCRC 585-275-2740 Carol_Greisberger@urmc.rochester.edu
Principal Investigator: Amneris E. Luque, MD
AIDS Community Health Ctr. ACTG CRS	Not yet recruiting
Rochester, New York, United States, 14604
Contact: Carol Greisberger, RN, CCRC 585-275-2740 Carol_Greisberger@urmc.rochester.edu
Principal Investigator: Roberto Corales, DO
United States, North Carolina
Moses H. Cone Memorial Hosp. CRS	Not yet recruiting
Greensboro, North Carolina, United States, 27401
Contact: Kim Epperson, RN 336-832-7888 kim.epperson@mosescone.com
Principal Investigator: Timothy Lane
United States, Ohio
Case CRS	Not yet recruiting
Cleveland, Ohio, United States, 44106
Contact: Jane Baum, RN 216-844-2546 baum.jane@clevelandactu.org
Principal Investigator: Michael M. Lederman, MD
The Ohio State Univ. AIDS CRS	Not yet recruiting
Columbus, Ohio, United States, 43210
Contact: Todd L. Lusch 614-293-5282 todd.lusch@osumc.edu
Principal Investigator: Susan L. Koletar, MD
Univ. of Cincinnati CRS	Not yet recruiting
Cincinnati, Ohio, United States, 45267-0405
Contact: Tammy Mansfield, RN, ACRN 513-584-8373 mansfitl@ucmail.uc.edu
Principal Investigator: Judith Feinberg, MD
United States, Rhode Island
The Miriam Hospital	Recruiting
Providence, Rhode Island, United States, 02906
Contact: Pamela Poethke, RN 401-793-4971 ppoethke@lifespan.org
Principal Investigator: Karen T. Tashima, MD
United States, Tennessee
Vanderbilt Therapeutics CRS	Not yet recruiting
Nashville, Tennessee, United States, 37203
Contact: Deborah Sutherland 615-467-0154 ext 109 deborah.sutherland@vanderbilt.edu
Principal Investigator: David W. Haas, MD
United States, Texas
Houston AIDS Research Team	Recruiting
Houston, Texas, United States, 77030
Contact: Hilda Cuervo 713-500-6751 Hilda.cuervo@uth.tmc.edu
Principal Investigator: Robert C. Arduino, MD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Adult AIDS Clinical Trials Group

Investigators

Study Chair:

Joseph J. Eron, Jr., MD

The University of North Carolina, Chapel Hill

More Information

Additional Information:

Click here for more information about darunavir This link exits the ClinicalTrials.gov site

Click here for more information about raltegravir This link exits the ClinicalTrials.gov site

Click here for more information about ritonavir This link exits the ClinicalTrials.gov site

Publications:

Capetti AF, Piconi S, Landonio S, Rizzardini G, Perno CF. Is Dual Therapy With Raltegravir and Protease Inhibitors a Feasible Option in Rescue Strategy in HIV-1 Infection? J Acquir Immune Defic Syndr. 2009 Feb 1;50(2):233-4. No abstract available.

Long MC, King JR, Acosta EP. Pharmacologic aspects of new antiretroviral drugs. Curr HIV/AIDS Rep. 2009 Feb;6(1):43-50.

Vermeir M, Lachau-Durand S, Mannens G, Cuyckens F, van Hoof B, Raoof A. Absorption, Metabolism, and Excretion of Darunavir, a New Protease Inhibitor, Administered Alone and with Low-Dose Ritonavir in Healthy Subjects. Drug Metab Dispos. 2009 Jan 8; [Epub ahead of print]

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5262
Study First Received:	January 26, 2009
Last Updated:	May 4, 2009
ClinicalTrials.gov Identifier:	NCT00830804 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Treatment Naive

Study placed in the following topic categories:

Sexually Transmitted Diseases, Viral
HIV Protease Inhibitors
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Antiviral Agents
Immunologic Deficiency Syndromes
Darunavir

Protease Inhibitors
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Retroviridae Infections

Additional relevant MeSH terms:

Anti-Infective Agents
HIV Protease Inhibitors
RNA Virus Infections
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Infection
Antiviral Agents

Pharmacologic Actions
Darunavir
Immunologic Deficiency Syndromes
Protease Inhibitors
Virus Diseases
Anti-Retroviral Agents
HIV Infections
Ritonavir
Therapeutic Uses
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections

ClinicalTrials.gov processed this record on May 06, 2009