Raltegravir + Lopinavir/Ritonavir Versus Efavirenz + Tenofovir + Emtricitabine in Treatment Naive Patients

Condition(s) targeted: HIV Infections

Intervention: Kaletra + Isentress (Drug); Atripla (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: California Collaborative Treatment Group

Overall contact:
Miguel Goicoechea, M.D., Phone: 619-543-8080, Ext: 274, Email: mgoicoechea@ucsd.edu

CCTG 589 is a randomized, open-label, pilot study comparing the efficacy, safety and tolerability of RAL plus LPV/r to EFV plus TDF/FTC in HIV-infected, treatment-naïve subjects. Subjects will be ineligible if they have any evidence of drug resistant virus in the past or at the time of screening (if never previously tested). Those who are found to be eligible will be randomized 1: 1 to initiate either LPV/r (400/100 mg) plus RAL (400mg), both given twice-daily, or fixed dose combination of EFV (600 mg), TDF (300 mg) and FTC (200 mg) given as once-daily Atripla® for 48 weeks.

Hypotheses

1. The novel nucleoside-sparing combination of LPV/r + RAL will have a faster phase 1 viral decay rate compared to standard-of-care therapy with EFV/TDF/FTC in antiretroviral-naïve patients.

1. Faster phase 1 viral decay dynamics will be associated with improved longer-term (week 48) viral suppression.

2. Faster phase 1 viral decay dynamics will be associated with accelerated early (Day 0-14) clearance of cell-associated HIV DNA.

3. Faster phase 1 viral decay dynamics will be associated with greater early (baseline to week 12) CD4+ T-cell recovery.

2. The LPV/r + RAL arm will have greater decreases in early (baseline to week 4) CD4/CD8 T-cell immune activation and apoptosis which will be associated with greater late (week 12 to week 48) CD4+ T-cell recovery.

3. Subjects treated with LPV/r + RAL arm will have smaller changes in total cholesterol and triglycerides from baseline than those receiving EFV/TDF/FTC.

Official title: Nucleoside-Sparing Combination Therapy With Lopinavir/Ritonavir (LPV/r) + Raltegravir (RAL) vs. Efavirenz (EFV) + Tenofovir Disoproxil Fumarate + Emtricitabine (TDF/FTC) in Antiretroviral-Naïve Patients

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Primary outcome: To compare the phase 1 viral decay rates between LPV/r + RAL vs. EFV/TDF/FTC treatment combinations.

Secondary outcome:

To determine the antiviral efficacy of LPV/r + RAL compared to EFV/TDF/FTC after 48 weeks of treatment.

To compare early (baseline to week 12) and late (week 12 to week 48) CD4+ T-cell recovery rates between treatment regimens.

To evaluate the association of phase 1 viral decay dynamics (baseline to day 14) on phase 1 (baseline to week 12) CD4+ T-cell recovery.

To evaluate the association of early changes in immune subsets (baseline to week 4) on phase 2 (week 12 to week 48) CD4+ T-cell recovery

To evaluate the safety and tolerability of this novel nucleoside-sparing combination of LPV/r + RAL compared to EFV/TDF/FTC therapy

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Documented HIV-1 infection.

- Treatment naïve (defined as having never received any HIV antiretroviral agents in

past).

- CD4+ T-cell count greater than or equal to 50 cells/mm3

- HIV viral load greater than or equal to 5,000 copies/mL

- Laboratory values obtained by screening laboratories within 30 days of entry:

- Absolute neutrophil count (ANC) greater than 750/mm3.

- Hemoglobin greater than 8. 0 g/dL.

- Platelet count greater than 50,000/mm3.

- Calculated creatinine clearance (CrCl) > 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)

- AST (SGOT), ALT (SGPT), and alkaline phosphatase less than 5 x ULN.

- Total bilirubin less than 2. 5 x ULN.

- Females of childbearing potential must have a negative serum pregnancy test at

screening and agree to use a double-barrier method of contraception throughout the study period.

- Men and women age greater than or equal to 18 years.

- Ability to obtain prescription for HIV antiretroviral medications and to have

required prescriptions filled prior to entry.

- Ability and willingness of subject to give written informed consent

Exclusion Criteria:

- Pregnancy or breast-feeding

- Serious illness requiring systemic treatment and/or hospitalization until subject

either completes therapy or is clinically stable on therapy, in the opinion of the investigator, for at least 30 days prior to study entry (day 0).

- Acute therapy for serious infection or other serious medical illnesses (in the

judgment of the site investigator) requiring systemic treatment and/or hospitalization within 14 days prior to study entry (day 0).

- Evidence of HIV seroconversion within 6 months prior to study entry.

- Evidence of any major HIV drug resistance-associated mutation on any genotype

performed prior to study entry or at the time of screening.

- History of chronic hepatitis C (defined as HCV antibody positive and HCV RNA

detectable).

- History of chronic active hepatitis B (defined as surface antigen positive and/or HBV

DNA detectable).

- Active drug or alcohol use or dependence that, in the opinion of the investigator,

would interfere with adherence to study requirements.

- Use of any immunomodulator, HIV vaccine, or investigational therapy within 30 days of

study entry.

- Use of human growth hormone within 30 days prior to study entry.

- Initiation of testosterone or anabolic steroids within 30 days prior to study entry.

(Exception: Chronic replacement dosages in patient's with diagnosed hypogonadism is allowed).

Miguel Goicoechea, M.D., Phone: 619-543-8080, Ext: 274, Email: mgoicoechea@ucsd.edu

University California San Diego, San Diego, California 92103, United States; Recruiting
Miguel Goicoechea, MD, Phone: 619-543-8080, Ext: 274, Email: mgoicoechea@ucsd.edu
Kathy Nuffer, RN, Phone: 619-543-8080, Ext: 225, Email: knuffer@ucsd.edu
Miguel Goicoechea, MD, Principal Investigator

Living Hope Clinical Foundation, Long Beach, California 90813, United States; Recruiting
Ron Yolo, RN, Phone: 562-624-4943, Email: ryolo@livinghopefoundation.com
Stephan Schneider, MD, Sub-Investigator

Desert AIDS Project, Palm Springs, California 92262, United States; Recruiting
Ivan Womboldt, CCRC, Phone: 760-320-9505, Email: iwomboldt@mydohc.com
Shubha Kerkar, MD, Sub-Investigator

Harbor-UCLA, Torrance, California 90502, United States; Recruiting
Angela Grbic, RN, Phone: 310-222-3848, Email: agrbic@labiomed.org
Eric Daar, MD, Principal Investigator

Univerisity California Irvine, Orange, California 92868, United States; Recruiting
Bobi Keenan, RN, Phone: 714-456-7747, Email: bobki@uci.edu
Jeremiah Tilles, MD, Sub-Investigator

University Southern California, Los Angeles, California 90033, United States; Recruiting
Connie Funk, RN, Phone: 323-343-8282, Email: funk@usc.edu
Luis Mendez, RN, Phone: 323-343-8283, Email: lmendez@usc.edu
Michael Dube, MD, Sub-Investigator

Starting date: September 2008
Last updated: September 15, 2008