Comparative Study of Three NNRTI-Sparing HAART Regimens - Full Text View

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Bristol-Myers Squibb Gilead Sciences Merck Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00811954

Purpose

The U.S. Department of Health and Human Services (HHS) guidelines recommend that HIV infected patients who have never received anti-HIV therapy be treated with a triple drug regimen. The most commonly prescribed and successful regimen contains the medication efavirenz (EFV). However, this regimen has been shown to cause undesirable side effects for some patients and is therefore not an option. Alternative regimens are needed for these patients.

This study will look at how well different combinations of anti-HIV drugs work to decrease the amount of HIV in the blood (viral load) of and allow immune system recovery in people who have never received anti-HIV therapy.

This study will also examine drug tolerability and safety for the various drug combinations.

Condition	Intervention	Phase
HIV Infections	Drug: Emtricitabine/tenofovir disoproxil fumarate Drug: Raltegravir Drug: Darunavir Drug: Ritonavir	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	A Phase III Comparative Study of Three Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Sparing Antiretroviral Regimens for Treatment-Naive HIV-1-Infected Volunteers

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Tenofovir Ritonavir Tenofovir disoproxil Tenofovir Disoproxil Fumarate Darunavir Raltegravir

U.S. FDA Resources

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

Primary Outcome Measures:

Time to virologic failure defined as the time from randomization to the first of two consecutive HIV-1 RNA levels [ Time Frame: At or after Week 16 and before Week 24 or after study Week 24 ] [ Designated as safety issue: No ]
Discontinuation of the RAL or PI component of randomized treatment for toxicity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Occurrence of new Grade 2, 3, or 4 sign or symptom or Grade 3 or 4 laboratory toxicity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Time to loss of virologic response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Presence of mutations associated with PI, NRTI, or RAL resistance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Number of drug classes with evidence of resistance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
CD4 counts and CD4 count changes from baseline [ Time Frame: At Weeks 4, 24, 48, 96, and 144 ] [ Designated as safety issue: No ]
Death or AIDS defining condition [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Targeted serious non-AIDS defining events including CDC category B [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Changes from baseline in fasting total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, glucose, Framingham 10-year risk, and self-reported rates of body shape changes in the three study regimens [ Time Frame: At Weeks 48, 96, and 144 ] [ Designated as safety issue: No ]
Risk behavior defined as the number of unprotected insertive or receptive anal or vaginal intercourse without the use of a condom in the preceding month [ Time Frame: At Weeks 48, 96, and 144 ] [ Designated as safety issue: No ]
Perception of infectiousness [ Time Frame: At Weeks 48, 96, and 144 ] [ Designated as safety issue: No ]
Self-reported adherence [ Time Frame: At Weeks 4, 24, 48, 96, and 144 ] [ Designated as safety issue: No ]
Pregnancy outcomes [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:

1800

Arms	Assigned Interventions
Group A: Experimental Participants will be administered emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), ritonavir (RTV), and atazanavir (ATV) to be taken orally, once daily for the entire duration of the study	Drug: Emtricitabine/tenofovir disoproxil fumarate A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Drug: Ritonavir A protease inhibitor (PI)
Group B: Experimental Participants will be administered FTC/TDF orally, once daily, and raltegravir (RAL) orally, twice daily, for the entire duration of the study	Drug: Emtricitabine/tenofovir disoproxil fumarate A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Drug: Raltegravir An integrase inhibitor
Group C: Experimental Participants will be administered FTC/TDF, darunavir (DRV), and RTV, orally, once daily for the entire duration of the study	Drug: Emtricitabine/tenofovir disoproxil fumarate A combination drug of two nucleoside reverse transcriptase inhibitors (NRTIs) Drug: Darunavir A protease inhibitor (PI) Drug: Ritonavir A protease inhibitor (PI)

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Eligibility

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

Criteria

Inclusion Criteria:

HIV infected
No evidence of any exclusionary mutations defined as any major NRTI or PI resistance-associated mutation on any genotype or evidence of significant NRTI or PI resistance on any phenotype performed at any time prior to study entry. NNRTI-associated resistance mutations are not excluded. More information on this criterion can be found in the study protocol.
No prior anti-HIV therapy. More information on this criterion can be found in the study protocol.
Viral load is 1000 copies/mL or higher, as measured within 90 days prior to study entry
Certain laboratory values obtained within 30 days prior to study entry
Ability to obtain RTV by prescription
Completed cardiovascular risk assessment. More information on this criterion can be found in the study protocol.
Must agree to use acceptable forms of contraception while receiving study drugs and for 6 weeks after stopping the medications. More information on this criterion is available in the protocol.

Exclusion Criteria:

Use of immunomodulators, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry
Known allergy or sensitivity to study drugs or their ingredients. A history of sulfa allergy is not excluded.
Any condition that, in the opinion of the investigator, would compromise the participant's ability to participate in the study
Serious illness requiring systemic treatment and/or hospitalization until participant either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 7 days prior to study entry
Requirement for any current medications that are prohibited with any study drugs
Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness
Any prior use of entecavir for treatment of hepatitis B for greater than 8 weeks while the participant was known to be HIV infected
Presence of Child Pugh Class C hepatic impairment
Presence of decompensated cirrhosis
Pregnant or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00811954

Show 29 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Bristol-Myers Squibb

Gilead Sciences

Merck

Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA

Investigators

Study Chair:	Jeffrey L. Lennox, MD	Emory HIV/AIDS CTU
Study Chair:	Judith Silverstein Currier, MD, MSc	UCLA AIDS Prevention & Treatment CTU
Principal Investigator:	Todd T. Brown, MD, PhD	JHU
Principal Investigator:	Grace McComsey, MD	Case CRS
Principal Investigator:	Susan Ellen Cohn, MD, MPH	Univ. of Rochester ACTG CRS

More Information

Additional Information:

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

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

Click here for more information about emtricitabine/tenofovir disoproxil fumarate 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:

Bartlett JA, Chen SS, Quinn JB. Comparative efficacy of nucleoside/nucleotide reverse transcriptase inhibitors in combination with efavirenz: results of a systematic overview. HIV Clin Trials. 2007 Jul-Aug;8(4):221-6. Review.

Duvivier C, Ghosn J, Assoumou L, Soulié C, Peytavin G, Calvez V, Génin MA, Molina JM, Bouchaud O, Katlama C, Costagliola D; ANRS 121 study group. Initial therapy with nucleoside reverse transcriptase inhibitor-containing regimens is more effective than with regimens that spare them with no difference in short-term fat distribution: Hippocampe-ANRS 121 Trial. J Antimicrob Chemother. 2008 Oct;62(4):797-808. Epub 2008 Jul 18.

Markowitz M, Nguyen BY, Gotuzzo E, Mendo F, Ratanasuwan W, Kovacs C, Prada G, Morales-Ramirez JO, Crumpacker CS, Isaacs RD, Gilde LR, Wan H, Miller MD, Wenning LA, Teppler H; Protocol 004 Part II Study Team. Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. J Acquir Immune Defic Syndr. 2007 Oct 1;46(2):125-33.

Molina JM, Andrade-Villanueva J, Echevarria J, Chetchotisakd P, Corral J, David N, Moyle G, Mancini M, Percival L, Yang R, Thiry A, McGrath D; CASTLE Study Team. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008 Aug 23;372(9639):646-55.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5257
Study First Received:	December 18, 2008
Last Updated:	August 26, 2009
ClinicalTrials.gov Identifier:	NCT00811954 History of Changes
Health Authority:	United States: Food and Drug Administration

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

Treatment naive
Treatment inexperienced

Study placed in the following topic categories:

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

Anti-Retroviral Agents
Emtricitabine
Integrase Inhibitors
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Tenofovir
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Reverse Transcriptase Inhibitors
Emtricitabine
Anti-Retroviral Agents
Therapeutic Uses
Tenofovir
Retroviridae Infections
Nucleic Acid Synthesis Inhibitors
Tenofovir disoproxil

RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Virus Diseases
HIV Infections
Sexually Transmitted Diseases
Lentivirus Infections

ClinicalTrials.gov processed this record on September 03, 2009