Study of Lopinavir/ Ritonavir and Lamivudine Versus Standard Therapy in Naïve HIV-1 Infected Subjects. (GARDEL)

A Phase 3, Randomized, Open Label, Controlled Study of Lopinavir/Ritonavir and Lamivudine Versus Standard Therapy in Naïve HIV-1 Infected Subjects.

The purpose of this study is designed to compare the safety, tolerability, antiviral activity and immunological effect of lopinavir/ritonavir plus lamivudine (3TC) versus standard therapy with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) plus lopinavir/ritonavir in the treatment of naïve HIV-1 infected subjects.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: lopinavir/ritonavir plus one nucleoside; Drug: lopinavir /ritonavir plus two nucleosides

Detailed Description

Combination therapy with 2 nucleoside reverse transcriptase inhibitors (NRTI) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) has been the mainstay of therapy for over 10 years, based on sound evidence derived from randomized controlled clinical trials and epidemiological data.A variety of new approaches designed to address the problems associated with combination highly active antiretroviral therapy (HAART) are currently being explored. These include strategic treatment interruptions to reduce time on therapy, toxicity and cost;Based on its performance, a dual drug combination that includes lopinavir/ritonavir and spares the more toxic NRTIs such as thymidine nucleoside-analogs, but maintains non-thymidine nucleoside-analogs appears as a potentially simple, safe and effective regimen.

• Study Type: Interventional
• Enrollment (Actual): 417
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad de Buenos Aires, Argentina, C1202ABB
    • Fundación Huésped

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. > 18 years of age.
2. Patient with documented HIV-1 infection
3. Subject has voluntarily signed and dated an informed consent form
4. Subject agrees not to take any medication during the study, including over the counter medicines or herbal preparations, without the approval of the trial physician.
5. Documented HIV-1 RNA >1,000 copies/mL
6. Subject naïve to ARV. (Patients who had received ARV ≤ 48 hours are allowed).
7. Subject has indication to receive an antiretroviral regimen.
8. Subjects can comply with protocol requirements.
9. Subject's general medical condition, in the investigator's opinion, does not interfere with assessments and completion of the trial.

10. If female, :

    1. use 2 different methods of birth control including, at least, one barrier method, and are acceptable to both the subject and investigator, and
    2. has a urine pregnancy test performed at the Screening Visit and on Baseline. Results of both tests must be negative.
    3. continue using 2 different methods of birth control including, at least, one barrier method for at least 30 days after the end of the treatment period

Exclusion Criteria:

• 1. Evidence of viral resistance against lopinavir/ritonavir, and/or FTC or 3TC, and/or other nucleoside analogues based on the genotype resistance test performed at screening, considering resistance according to the panel IAS - USA, version in December, 2009.

  2. The presence of any of the following major mutations: V32I; I47V / A; L76V; V82A/F/T/S or the presence of two or more minor mutations at positions:10,20,24,33,46,50,53,54,63,71,73,84,90 is considered resistance to lopinavir/ritonavir.

  3. The presence of mutation M184V/I and/or K65R is considered resistance to 3TC or FTC. At the discretion of the investigator and based on the resistance test, a treatment based on lopinavir / ritonavir, plus 3TC or FTC and other similar nucleoside / nucleotide active could not be constructed.

  4. Previously documented HIV-2 infection. 5. Use of disallowed concomitant therapy 6. Patient has a current (active) diagnosis of acute hepatitis due to any cause OR chronic Hepatitis C WITH aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >5 x upper limit of normal (ULN) AND/OR is likely to require treatment in the next year.

  7. Active Hepatitis B infection (regardless of stage of infection). 8. Any active clinically significant disease . 9. Subject has a currently active AIDS defining illness (Category C)30 days of screening. Subjects who are on stable maintenance therapy for an opportunistic infection may be enrolled.

  10. Life expectancy < 1 year according to the judgment of the investigator. 11. Screening laboratory analysis shows any of the following abnormal laboratory results:

  a. Hemoglobin < 8.0 g/dL b. Absolute neutrophil count < 750 cells/µL c. Platelet count < 50,000 mm3 d. Creatinine> 1.5 times the normal upper limit. 12. Subject enrolled in other clinical trials . 13. Use of any investigational agents within 30 days prior to screening. 14. Use of immunosuppressive drugs, cytokine inhibitors or other cytokines in the last year.

  15. Active substance use or abuse that the investigator determines may significantly interfere with study procedures 16. Any condition (including but not limited to alcohol and drug use) which in the opinion of the investigator, could compromise the subject's safety or adherence to the protocol.

  17. Subject is pregnant or breast-feeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: lopinavir/ritonavir plus lamivudine; ARM 1: Lopinavir/ritonavir 200mg/50mg 2 tabs bid plus 3TC 150mg x1 tab bid	Drug: lopinavir/ritonavir plus one nucleoside; ARM 1: Lopinavir/ritonavir 200mg/50mg 2 tabs bid plus 3TC 150mg x1 tab bid
Active Comparator: lopinavir/ritonavir plus two nucleosides; ARM 2: 3TC 150mg x1 tab bid or FTC 200mg 1 capsule qd plus Lopinavir/ritonavir 200mg/50mg 2 tabs BID plus a second NRTI, selected at investigator's discretion, based on baseline genotype	Drug: lopinavir /ritonavir plus two nucleosides; ARM 2: 3TC 150mg x1 tab bid or FTC 200mg 1 capsule qd plus Lopinavir/ritonavir 200mg/50mg 2 tabs BID plus a second NRTI, selected at investigator's discretion, based on baseline genotype.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
• Proportion of patients with HIV-1 RNA levels of less than 50 copies/mL in an intent-to-treat analysis at week 48	48 and 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
• Proportion of patients with HIV-1 RNA levels of less than 400 copies/mL at week 24 and at week 48	Proportion of patients with HIV-1 RNA levels of less than 50 copies/mL at week 24.; Number and type of resistance mutations in case of virologic failure• CD4+ lymphocyte count and proportion evolution between baseline and week 24 and 48.; Comparison of lipid profiles after 48 weeks; Changes in quality of life, assessed by a validated questionnaire; Treatment survival and interruptions.; Frequency, type and severity of adverse events.; Frequency of opportunistic infections (OI) and disease progression.	48 weeks

Collaborators and Investigators

• Sponsor: Pedro Cahn
• Collaborators: Abbott
• Investigators: Principal Investigator: Pedro Cahn, MD, PhD, Fundación Huésped

Publications and helpful links

General Publications

• Cahn P, Andrade-Villanueva J, Arribas JR, Gatell JM, Lama JR, Norton M, Patterson P, Sierra Madero J, Sued O, Figueroa MI, Rolon MJ; GARDEL Study Group. Dual therapy with lopinavir and ritonavir plus lamivudine versus triple therapy with lopinavir and ritonavir plus two nucleoside reverse transcriptase inhibitors in antiretroviral-therapy-naive adults with HIV-1 infection: 48 week results of the randomised, open label, non-inferiority GARDEL trial. Lancet Infect Dis. 2014 Jul;14(7):572-80. doi: 10.1016/S1473-3099(14)70736-4. Epub 2014 Apr 27.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: November 8, 2010
• First Submitted That Met QC Criteria: November 8, 2010
• First Posted (Estimate): November 9, 2010

Study Record Updates

• Last Update Posted (Estimate): June 12, 2012
• Last Update Submitted That Met QC Criteria: June 8, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Lopinavir/ritonavir plus 3TC as a dual therapy regimen.
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lopinavir
• Other Study ID Numbers: FH-10 GARDEL study