HIV InfectionsNCT00525733
Standard Antiretroviral v. Multi-class Therapy in Acutely HIV-1 Infected Antiretroviral-Naïve Subjects (ADARC 2007-01)
A study testing darunavir 800 mg, FTC 200 mg/TDF 300mg and Maraviroc in people with HIV Infections, run by Rockefeller University at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- darunavir 800 mg, FTC 200 mg/TDF 300mg and Maraviroc
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2007to Dec 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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-
- Gault equation:
- For men, (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) = CrCl (mL/min)
- For women, multiply the result by 0.85 = CrCl (mL/min) NOTE: A program to assist in calculations is available on the DMC web site at: http://www.fstrf.org/ACTG/ccc.html
- For women of reproductive potential, negative serum or urine pregnancy test within 48 hours prior to initiating study medications unless otherwise specified by product labeling.
- Female candidates of reproductive potential is defined as girls who have reached menarche or women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) or have not undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation).
- Contraception requirements:
- Female candidates of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree that they will use at least one reliable method of contraception while receiving the protocol-specified drugs and for 6 weeks after stopping the medications.
- Male Candidates:
- If you are a heterosexual male, you and your sexual partner must agree to use acceptable methods of birth control during the entire study.
- Acceptable methods of birth control include intrauterine device (IUD), diaphragm with spermicide, condoms or not having sex.
- Oral contraceptives alone are not an acceptablemethod of birth control.
- Men and women age ≥ 18 years.
- Ability and willingness of subject to give written informed consent.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Rockefeller University
New York, New York, 10021
The Rockefeller University
New York, New York, 10065
About this study
Official title: A Phase II, Randomized Trial of Open-Label Truvada With Darunavir/Ritonavir Versus Multiclass Therapy With Truvada, Darunavir/Ritonavir, Maraviroc and Raltegravir in Acutely HIV-1 Infected Antiretroviral-Naïve Subjects
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.
Read the detailed description
- DURATION: 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.
- SAMPLE SIZE: 36 subjects randomized 2:1 multi-class versus standard antiretroviral therapy.
- POPULATION: Acutely HIV-1-infected, antiretroviral (ARV) drug-naïve (≤ 7 days of ARV treatment at anytime prior to study entry*) men and women ≥ 18 years of age.
- REGIMEN: At entry subjects will be randomized to one of the following in a 1:2 ratio:
ARM A: FTC 200 mg/TDF 300 mg QD + darunavir 800 mg/ritonavir 100 mg QD
ARM B: FTC 200 mg/TDF 300 mg QD + darunavir 800mg/ritonavir 100 mg QD + Raltegravir 400 mg BID + Maraviroc 150 mg BID
The three primary objectives are:
- To assess whether a multi-class regimen could completely suppress virus replication in HIV infected individuals based on:
- Plasma HIV-1 RNA levels at 48 weeks
- Ultrasensitive < 50 copy assay
- 5 copy assay
- 1 copy assay
- Cell associated HIV-1RNA levels at week 48
- Proviral DNA
- Levels at week 48
- Decay rates from week 12 to week 48
- To determine whether multi-class antiviral therapy results in enhanced immune reconstitution in peripheral blood and gastrointestinal mucosa based on flow and immunohistochemistry.
- To assess tolerability of multi-class compact antiviral therapy to that of standard compact antiviral therapy.
- Conditions
- HIV Infections
- Being tested
- darunavir 800 mg, FTC 200 mg/TDF 300mg, Maraviroc, Raltegravir, Ritonavir 100 mg
- Keywords
- HIV-1, Acute Infection, Treatment Naive
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
darunavir 800 mgDrug
Also called prezista
darunavir 800mg tablet will be administered with 100 mg capsule of ritonavir once daily (may be taken with or without food)
FTC 200 mg/TDF 300mgDrug
Also called FTC/TDF
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)
MaravirocDrug
Also called selzentry
Maraviroc will be administered twice daily in 150 mg tablets (may be taken with or without food)
RaltegravirDrug
Also called isentress
Raltegravir will be administered twice daily as 1-400 mg tablets (to be taken with food)
Ritonavir 100 mgDrug
Also called norvir
one tablet of ritonavir is taken with darunavir daily
| Study group | Role | What they receive |
|---|---|---|
| 3-drug standard therapy | Active comparator | FTC 200 mg/TDF 300 mg QD + darunavir 800 mg/ +ritonavir 100 mg QD Receives: 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 Receives: Drug: darunavir 800 mg; Drug: FTC 200 mg/TDF 300mg; Drug: Maraviroc; Drug: Raltegravir; Drug: Ritonavir 100 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2007 (estimated)
- Study startOct 2007
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rockefeller University
- Sponsor type
- University, hospital or other
- Collaborators
- Aaron Diamond AIDS Research Center, Merck Sharp & Dohme LLC, Pfizer
- Responsible party
- Sponsor
- Investigators
- Martin Markowitz, MD, Principal investigator, Rockefeller University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00525733
- Sponsor's protocol ID
- MMA-0610-0607
- Status last verified
- Jan 2015
- First submitted
- 5 Sep 2007
- Last updated
- 9 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized Trial of Open-Label Truvada With Darunavir/Ritonavir Versus Multiclass Therapy With Truvada, Darunavir/Ritonavir, Maraviroc and Raltegravir in Acutely HIV-1 Infected Antiretroviral-Naïve Subjects
- ClinicalTrials.gov ID
- NCT00525733
- Acronym / sponsor ID
- MMA-0610-0607
- Conditions
- HIV Infections
- Keywords
- HIV-1, Acute Infection, Treatment Naive
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Rockefeller UniversityUniversity, hospital or other
- Collaborators
- Aaron Diamond AIDS Research Center, Merck Sharp & Dohme LLC, Pfizer
- Study start
- Oct 2007
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 6 Sep 2007 (estimated)
- Results
- Posted 9 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- DURATION: 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.
- SAMPLE SIZE: 36 subjects randomized 2:1 multi-class versus standard antiretroviral therapy.
- POPULATION: Acutely HIV-1-infected, antiretroviral (ARV) drug-naïve (≤ 7 days of ARV treatment at anytime prior to study entry*) men and women ≥ 18 years of age.
- REGIMEN: At entry subjects will be randomized to one of the following in a 1:2 ratio:
ARM A: FTC 200 mg/TDF 300 mg QD + darunavir 800 mg/ritonavir 100 mg QD
ARM B: FTC 200 mg/TDF 300 mg QD + darunavir 800mg/ritonavir 100 mg QD + Raltegravir 400 mg BID + Maraviroc 150 mg BID
The three primary objectives are:
- To assess whether a multi-class regimen could completely suppress virus replication in HIV infected individuals based on:
- Plasma HIV-1 RNA levels at 48 weeks
- Ultrasensitive < 50 copy assay
- 5 copy assay
- 1 copy assay
- Cell associated HIV-1RNA levels at week 48
- Proviral DNA
- Levels at week 48
- Decay rates from week 12 to week 48
- To determine whether multi-class antiviral therapy results in enhanced immune reconstitution in peripheral blood and gastrointestinal mucosa based on flow and immunohistochemistry.
- To assess tolerability of multi-class compact antiviral therapy to that of standard compact antiviral therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 3-drug standard therapy | Active comparator | Drug: darunavir 800 mg, Drug: FTC 200 mg/TDF 300mg, Drug: Ritonavir 100 mgFTC 200 mg/TDF 300 mg QD + darunavir 800 mg/ +ritonavir 100 mg QD |
| 5-drug experimental therapy | Experimental | Drug: darunavir 800 mg, Drug: FTC 200 mg/TDF 300mg, Drug: Maraviroc, Drug: Raltegravir, Drug: Ritonavir 100 mgFTC 200 mg/TDF 300 mg QD + darunavir 800 mg + ritonavir 100 mg QD + Raltegravir 400 mg BID + Maraviroc 150 mg BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- Acute HIV-1 infection defined as:
- Antiretroviral (ARV) drug-naïve (defined as ≤ 7 days of ARV treatment at any time prior to entry*).
- The only exceptions are:
- Laboratory values obtained within 30 days prior to study entry.
- For men, (140 - age in years) x (body weight in kg) ÷ (serum creatinine in mg/dL x 72) = CrCl (mL/min)
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| darunavir 800 mgAlso: prezistadarunavir 800mg tablet will be administered with 100 mg capsule of ritonavir once daily (may be taken with or without food) | Drug | 3-drug standard therapy, 5-drug experimental therapy |
| FTC 200 mg/TDF 300mgAlso: FTC/TDFEmtricitabine/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) | Drug | 3-drug standard therapy, 5-drug experimental therapy |
| MaravirocAlso: selzentryMaraviroc will be administered twice daily in 150 mg tablets (may be taken with or without food) | Drug | 5-drug experimental therapy |
| RaltegravirAlso: isentressRaltegravir will be administered twice daily as 1-400 mg tablets (to be taken with food) | Drug | 5-drug experimental therapy |
| Ritonavir 100 mgAlso: norvirone tablet of ritonavir is taken with darunavir daily | Drug | 3-drug standard therapy, 5-drug experimental therapy |
Primary outcome
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.
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The Rockefeller University HospitalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Markowitz, MD principal investigator
Rockefeller University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing darunavir 800 mg, FTC 200 mg/TDF 300mg and Maraviroc in people with HIV Infections, run by Rockefeller University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 48 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2015.