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

NCT00752856 | Completed Phase 2 Results DMC

• 1 other identifier: CCTG 589
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 6

Brief Summary

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. 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.
2. 2.Faster phase 1 viral decay dynamics will be associated with improved longer-term (week 48) viral suppression.
3. 3.Faster phase 1 viral decay dynamics will be associated with accelerated early (Day 0-14) clearance of cell-associated HIV DNA.
4. 4.Faster phase 1 viral decay dynamics will be associated with greater early (baseline to week 12) CD4+ T-cell recovery.
5. 5.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.
6. 6.Subjects treated with LPV/r + RAL arm will have smaller changes in total cholesterol and triglycerides from baseline than those receiving EFV/TDF/FTC.

Conditions

HIV Infections

Keywords

HIV treatment; Treatment-naive; Adult

Outcome Measures

Primary Outcomes (1)

• To Compare the Phase 1 Viral Decay Rates Between LPV/r + RAL vs. EFV/TDF/FTC Treatment Combinations.

  Repeated HIV RNA measured at different time points (baseline, days 2, 7, 10, 14) will be treated as the outcome variable in a linear mixed-effects model. The primary fixed effects will include time, treatment group, treatment group-by-time interaction; random effects will include both intercept and slope allowing each subject to have individual baseline viral load and viral decay (rate of decrease in viral load following initiation of antiretroviral therapy). The treatment group-by- time interaction term in the model will indicate the difference in viral decay rates between the two treatment groups. Baseline covariate adjustment will be included if necessary.

  Baseline, days 2, 7, 10, 14

Secondary Outcomes (3)

• Viral Suppression Efficacy at 48 Weeks

  48 weeks

• Compare Early Activated CD4+ T-cell Recovery Rates From Baseline to Week 4.

  Baseline to Week 4

• Compare Late Activated CD4+ T-cell Recovery Rates Between Treatment Regimens From Baseline to Week 48

  48 weeks

Study Arms (2)

1 - Kaletra + Isentress taken twice daily

EXPERIMENTAL

Kaletra (lopinavir/ritonavir 400/100 mg) + Isentress (Raltegravir 400 mg) twice-daily

Drug: Kaletra + Isentress

2 - Atripla taken once daily

ACTIVE COMPARATOR

Sustiva (EFV 600 mg), Viread (TDF 300 mg) and Emtriva (FTC 200 mg) taken as Atripla® once-daily

Drug: Atripla

Interventions

Kaletra + Isentress DRUG

kaletra 2 tabs twice a day + Raltegravir 1 tab twice a day

Also known as: Lopinavir/ritonavir (LPV/r) + Raltegravir (RAL)

1 - Kaletra + Isentress taken twice daily

Atripla DRUG

Atripla 1 tab once a day

Also known as: Efavirenz (EFV) + Tenofovir Disoproxil Fumarate + Emtricitabine (TDF/FTC)

2 - Atripla taken once daily

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of California, San Diego: lead
• California HIV/AIDS Research Program: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Abbott: collaborator

Study Sites (6)

Living Hope Clinical Foundation

Long Beach, California, 90813, United States

Location

University Southern California

Los Angeles, California, 90033, United States

Location

Univerisity California Irvine

Orange, California, 92868, United States

Location

Desert AIDS Project

Palm Springs, California, 92262, United States

Location

University California San Diego

San Diego, California, 92103, United States

Location

Harbor-UCLA

Torrance, California, 90502, United States

Location

Related Publications (1)

• Karris MY, Jain S, Bowman VQ, Rieg G, Goicoechea M, Dube MP, Kerkar S, Kemper C, Diamond C, Sun X, Daar ES, Haubrich RH, Morris S; California Collaborative Treatment Group (CCTG) 589 Study Team. Nucleoside-Sparing Regimens With Raltegravir and a Boosted Protease Inhibitor: An Unsettled Issue. J Acquir Immune Defic Syndr. 2016 Jun 1;72(2):e48-50. doi: 10.1097/QAI.0000000000000990. No abstract available.

  PMID: 26977746 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

lopinavir-ritonavir drug combination; Raltegravir Potassium; Lopinavir; Ritonavir; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; efavirenz; Tenofovir; Emtricitabine

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)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidinones; Pyrimidines; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Organophosphonates; Organophosphorus Compounds; Oxazines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Drug Combinations; Pharmaceutical Preparations; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Sheldon Morris
• Organization: UCSD

shmorris@ucsd.edu

8583364088

Study Officials

• Richard Haubrich, MD

  California Collaborative Treatment Group (CCTG)

  PRINCIPAL INVESTIGATOR

• Sheldon Morris, MD

  UC San Diego AntiViral Research Center (AVRC)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: September 13, 2008
• First Posted: September 16, 2008
• Study Start: August 26, 2008
• Primary Completion: May 5, 2011
• Study Completion: February 11, 2014
• Last Updated: July 22, 2020
• Results First Posted: July 7, 2020

Record last verified: 2020-07

Locations

US (6)