Study to Evaluate the Activity and Tolerability of Lopinavir/Ritonavir and Lamivudine Bitherapy in HIV Patients With Viral Suppression (OLE)

Study to Evaluate the Activity and Tolerability of Lopinavir/Ritonavir and Lamivudine Bitherapy Instead of a Triple Therapy That Includes Lopinavir/Ritonavir and Lamivudine or Emtricitabine in HIV Patients With Viral Suppression: Controlled Clinical Trial, Open Label, Randomized, of 48 Weeks of Follow-up

This is a prospective, open controlled trial in which HIV-1 with viral suppression patients will be randomized to continue with their current treatment (lopinavir/ritonavir plus emtricitabine or lamivudine plus any nucleoside analogue reverse transcriptase inhibitor) or to simplify to lopinavir/ritonavir plus lamivudine.

Randomization will be stratified according to the values of nadir CD4 and time of viral suppression.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: antiretroviral treatment

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial Barcelona
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz

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:

• Patients of either sex (female or male) and 18 years or older.
• Patients seropositive for HIV-1 using standard diagnostic criteria.
• There is confirmation of viral load to be lower than 50 cop/ml during the 6 previous months to inclusion. The requirement is to have at least two viral loads lower than 50 cop/mL separated by 6 months and no one >50cop/mL during the 6 months before inclusion.
• Patients on continuous HAART consisting of LPV/r, emtricitabine (FTC) or 3TC (lamivudine) and an NRTI for at least 2 months before being randomized in this study.
• Patients who are clinically stable, in the opinion of the investigator, at entry into the study (clinical status and chronic medication must not have not been modified at least 14 days prior to randomization). Patients receiving therapy for an active opportunistic infection are eligible for enrollment if the above criteria are met. Standard prophylaxis of opportunistic infections is permitted.

Exclusion Criteria:

• Pregnancy, nursing, or planned pregnancy during the study period.
• Previous failure with regimens including a protease inhibitor (PI) or 3TC/FTC.
• Known resistance mutations to PIs or 3TC/FTC.
• Patients with an active opportunistic infection or malignancy. Patients with a stable chronic opportunistic infection may be included in the study.
• Any disease or history of disease which, in the opinion of the investigator, might confound the results of the study or pose additional risk to patient treatment.
• Patients diagnosed with visceral Kaposi's sarcoma (KS), patients with lymphoedema secondary to cutaneous KS or cutaneous or palatine KS who have been treated with systemic immunosuppressive therapy must also be excluded.
• Patients with chronic hepatitis B on treatment with tenofovir + 3TC/FTC

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: simplification; Lopinavir/ritonavir (400/100 BID) plus lamivudine (300 QD)	Drug: antiretroviral treatment; antiretroviral treatment
Active Comparator: Continue with current treatment	Drug: antiretroviral treatment; antiretroviral treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with no treatment failure	viral failure, defined as two viral loads above 50 copies/ml at least two weeks apart; death; developing new CDC-C events; withdrawing consent; being lost to follow-up; switching assigned treatment for any cause	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with no viral failure	defined as two viral loads above 50 copies/ml. Patients lost to follow-up or changing treatment will not be taken into account for this analysis	48 weeks
Proportion of patients with no therapeutical failure	defined as in the primary outcome but with two viral loads above 400 copies/ml, not 50 as in the primary outcome.	48 weeks
Proportion of patients with no viral failure	defined as two viral loads above 400 copies/ml	48 weeks
Time to viral failure	Two different analysis will be carried out: with 50 copies/ml threshold and with 400 copies/ml threshold	48 weeks
Proportion of patients with blips	Defined as one viral load above 50 and below 400 copies/ml with next viral load below 50 copies/ml	48 weeks
Change from baseline CD4		48 weeks
Lipidic profile change from baseline		48 weeks
Creatinine clearance change from baseline		48 weeks
Proportion of patients with proximal tubular renal disfunction		48 weeks
Lipodystrophy changes from baseline	evaluated using two questionnaires: lipoatrophy and fat accumulation	48 weeks
Adherence to treatment		48 weeks
Mortality and progression to AIDS		48 weeks
Adverse events per treatment branch		48 weeks
Proportion of patients switching study treatment due to an adverse event		48 weeks
Proportion of serious adverse events related to treatment		48 weeks

Collaborators and Investigators

• Sponsor: Juan A. Arnaiz
• Investigators: Principal Investigator: José Ramón Arribas, MD, Hospital Uniuversitario La Paz

Publications and helpful links

General Publications

• Arribas JR, Girard PM, Landman R, Pich J, Mallolas J, Martinez-Rebollar M, Zamora FX, Estrada V, Crespo M, Podzamczer D, Portilla J, Dronda F, Iribarren JA, Domingo P, Pulido F, Montero M, Knobel H, Cabie A, Weiss L, Gatell JM; OLE/RIS-EST13 Study Group. Dual treatment with lopinavir-ritonavir plus lamivudine versus triple treatment with lopinavir-ritonavir plus lamivudine or emtricitabine and a second nucleos(t)ide reverse transcriptase inhibitor for maintenance of HIV-1 viral suppression (OLE): a randomised, open-label, non-inferiority trial. Lancet Infect Dis. 2015 Jul;15(7):785-92. doi: 10.1016/S1473-3099(15)00096-1. Epub 2015 Jun 7. Erratum In: Lancet Infect Dis. 2015 Aug;15(8):875.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: November 15, 2011
• First Submitted That Met QC Criteria: November 15, 2011
• First Posted (Estimate): November 16, 2011

Study Record Updates

• Last Update Posted (Estimate): July 29, 2014
• Last Update Submitted That Met QC Criteria: July 28, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• 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; Anti-Infective Agents; Antiviral Agents; Anti-Retroviral Agents
• Other Study ID Numbers: OLE