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

• Status: Completed
• Trial end date: 2013-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rockefeller University
• Collaborators: Aaron Diamond AIDS Research Center; Merck Sharp & Dohme Corp.; Pfizer
• Treatments: Darunavir; Maraviroc; Raltegravir Potassium; Ritonavir

Criteria

Inclusion Criteria:

• 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-

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.

Exclusion Criteria:

• 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.