Standard Antiretroviral v. Multi-class Therapy in Acutely HIV-1 Infected Antiretroviral-Naïve Subjects (ADARC 2007-01)

NCT00525733 | Completed Results

• 1 other identifier: MMA-0610-0607
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

The researchers are involved in a phase II, randomized, two-arm study, comparing the efficacy, safety, and tolerability of open-label ritonavir (RTV)-enhanced darunavir with Truvada to a 5-drug multi-class regimen including truvada, darunavir/ritonavir/maraviroc/and raltegravir on acutely HIV-1-infected, antiretroviral (ARV) drug-naïve men and women. Subjects will participate for at least 60 weeks and up to 96 weeks if in the opinion of the investigator and patient that continued therapy is in the patient's best interest. Hypotheses:

• Multi-class antiretroviral therapy (ART) is superior to RTV-enhanced ATV in combination with Emtricitabine/Tenofovir DF (FTC/TDF) with respect to suppression of viral replication.
• Multi-class ART is superior to RTV-enhanced ATV in combination with FTC/TDF with respect to immune reconstitution in peripheral blood and in the gastrointestinal mucosa.
• Multi-class ART is equivalent to RTV-enhanced ATV in combination with FTC/TDF with respect to tolerability.

Conditions

HIV Infections

Keywords

HIV-1; Acute Infection; Treatment Naive

Outcome Measures

Primary Outcomes (1)

• The Primary Outcome of This Study is the Proportion of Patients Having Detectable HIV-1 RNA Using the Single Copy Assay After 48 Weeks of Treatment and the Study Hypothesis is That New Treatment is Better Than the Control Group.

  48 weeks

Study Arms (2)

3-drug standard therapy

ACTIVE COMPARATOR

FTC 200 mg/TDF 300 mg QD + darunavir 800 mg/ +ritonavir 100 mg QD

Drug: darunavir 800 mg; Drug: FTC 200 mg/TDF 300mg; Drug: Ritonavir 100 mg

5-drug experimental therapy

EXPERIMENTAL

FTC 200 mg/TDF 300 mg QD + darunavir 800 mg + ritonavir 100 mg QD + Raltegravir 400 mg BID + Maraviroc 150 mg BID

Drug: darunavir 800 mg; Drug: FTC 200 mg/TDF 300mg; Drug: Maraviroc; Drug: Raltegravir; Drug: Ritonavir 100 mg

Interventions

darunavir 800 mg DRUG

darunavir 800mg tablet will be administered with 100 mg capsule of ritonavir once daily (may be taken with or without food)

Also known as: prezista

3-drug standard therapy; 5-drug experimental therapy

FTC 200 mg/TDF 300mg DRUG

Emtricitabine/tenofovir DF fixed-dose tablet containing 200 mg of emtricitabine and 300 mg of tenofovir DF will be administered orally as one tablet once daily (may be taken with or without food)

Also known as: FTC/TDF

3-drug standard therapy; 5-drug experimental therapy

Maraviroc DRUG

Maraviroc will be administered twice daily in 150 mg tablets (may be taken with or without food)

Also known as: selzentry

5-drug experimental therapy

Raltegravir DRUG

Raltegravir will be administered twice daily as 1-400 mg tablets (to be taken with food)

Also known as: isentress

5-drug experimental therapy

Ritonavir 100 mg DRUG

one tablet of ritonavir is taken with darunavir daily

Also known as: norvir

3-drug standard therapy; 5-drug experimental therapy

Eligibility Criteria

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

You may qualify if:

• Acute HIV-1 infection defined as:
• Negative ELISA/Western Blot or indeterminate Western Blot in the presence of HIV-1 RNA \> 5,000 copies/ml.
• Positive HIV-1 serology with a detuned ELISA O.D. value below 0.5.
• A documented negative serology within 180 days of screening and a positive HIV-1 serology at screening
• Antiretroviral (ARV) drug-naïve (defined as ≤ 7 days of ARV treatment at any time prior to entry\*).
• The only exceptions are:
• Use of antivirals as part of post-exposure prophylaxis (PEP) provided the subject did not acquire HIV-1 infection from the event that required PEP.
• Therapy with an investigational ARV drug that was not an NRTI, NNRTI, or PI.
• Laboratory values obtained within 30 days prior to study entry.
• Absolute neutrophil count (ANC) ≥ 500/mm3
• Hemoglobin ≥ 8.0 g/dL
• Platelet count ≥ 40,000/mm3
• AST (SGOT), ALT (SGPT), and alkaline phosphatase ≤ 7.5 × ULN
• Total bilirubin ≤2.5 x ULN
• Calculated creatinine clearance ≥60 mL/min as estimated by the Cockcroft-

You may not qualify if:

• Currently breast-feeding.
• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. NOTE: Subjects receiving stable physiologic glucocorticoid doses, defined as prednisone ≤ 10 mg/day, will not be excluded.
• Known allergy/sensitivity to study drugs or their formulations.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.
• NOTE: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) have no restriction.
• Clinically relevant cardiac conduction system disease. This includes severe first degree atrioventricular block (PR interval \> 0.26 seconds), or second, or third-degree atrioventricular block.
• Requirement for any current medications that are prohibited with any study treatment.
• Evidence of major resistance-associated mutations on genotype performed within 14 days of day 1. Major resistance-associated mutations include: NRTI: K65R or inserts Q151M, M184V/I, PI: I50L/V, I84V, N88S.
• Viral population that is either dual tropic or X4 tropic using the Monogram assay (patients will be entered and be treated pending this result performed within 28 days of day 1).
• Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical (e.g., infectious disease) illness.
• Participation in any other clinical trial within 30 days prior to screening.
• Any other clinical conditions or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the requirements.

Sponsors & Collaborators

• Rockefeller University: lead
• Aaron Diamond AIDS Research Center: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Pfizer: collaborator

Study Sites (2)

Rockefeller University

New York, New York, 10021, United States

Location

The Rockefeller University

New York, New York, 10065, United States

Location

Related Links

• The Rockefeller University Hospital

MeSH Terms

Conditions

HIV Infections

Interventions

Darunavir; Racivir; Maraviroc; Raltegravir Potassium; Ritonavir

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)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Pyrrolidinones; Pyrrolidines; Thiazoles

Results Point of Contact

• Title: Martin Markowitz MD
• Organization: Aaron Diamond AIDS Research Center

mmarkowitz@adarc.org

212-448-5020

Study Officials

• Martin Markowitz, MD

  Rockefeller University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2007
• First Posted: September 6, 2007
• Study Start: October 1, 2007
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: March 9, 2015
• Results First Posted: March 9, 2015

Record last verified: 2015-01

Locations

US (2)