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

NCT01237444 | Completed Phase 3 DMC

• 1 other identifier: FH-10 GARDEL study
• Study Type: interventional
• Target: 417
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV Infection

Keywords

Lopinavir/ritonavir plus 3TC as a dual therapy regimen.

Outcome Measures

Primary Outcomes (1)

• • 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 Outcomes (1)

• • Proportion of patients with HIV-1 RNA levels of less than 400 copies/mL at week 24 and at week 48

  48 weeks

Study Arms (2)

lopinavir/ritonavir plus lamivudine

EXPERIMENTAL

ARM 1: Lopinavir/ritonavir 200mg/50mg 2 tabs bid plus 3TC 150mg x1 tab bid

Drug: lopinavir/ritonavir plus one nucleoside

lopinavir/ritonavir plus two nucleosides

ACTIVE COMPARATOR

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

Interventions

lopinavir/ritonavir plus one nucleoside DRUG

ARM 1: Lopinavir/ritonavir 200mg/50mg 2 tabs bid plus 3TC 150mg x1 tab bid

lopinavir/ritonavir plus lamivudine

lopinavir /ritonavir plus two nucleosides DRUG

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.

lopinavir/ritonavir plus two nucleosides

Eligibility Criteria

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

You may qualify if:

• \> 18 years of age.
• Patient with documented HIV-1 infection
• Subject has voluntarily signed and dated an informed consent form
• 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.
• Documented HIV-1 RNA \>1,000 copies/mL
• Subject naïve to ARV. (Patients who had received ARV ≤ 48 hours are allowed).
• Subject has indication to receive an antiretroviral regimen.
• Subjects can comply with protocol requirements.
• Subject's general medical condition, in the investigator's opinion, does not interfere with assessments and completion of the trial.
• If female, :
• use 2 different methods of birth control including, at least, one barrier method, and are acceptable to both the subject and investigator, and
• has a urine pregnancy test performed at the Screening Visit and on Baseline. Results of both tests must be negative.
• 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

You may not qualify if:

• \. 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.
• \. 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.
• \. 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.
• \. 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.
• \. 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.
• \. 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.
• \. 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.
• \. Subject is pregnant or breast-feeding.

Sponsors & Collaborators

• Pedro Cahn: lead
• Abbott: collaborator

Study Sites (1)

Fundacion Huesped

Ciudad de Buenos Aires, C1202ABB, Argentina

Location

Related Publications (1)

• 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.

  PMID: 24783988 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

HIV Infections

Interventions

Lopinavir; Ritonavir

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)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles

Study Officials

• Pedro Cahn, MD, PhD

  FUNDACION HUESPED

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 8, 2010
• First Posted: November 9, 2010
• Study Start: December 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: June 12, 2012

Record last verified: 2012-06

Locations

AR (1)